CLSI 2020.pdf

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Standard@dsiorg

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A100. 30th ed.
Janvary 2020
Replaces M10D, 29h ed.

Performance Standards for Antimicrobial Susceptibility Testing

Melvin, Weinstein, MD ‘Thomas J. Kim. Jr, MD, PRD
James $. Lewis I, Pham, FIDSA Brandi Limbogo, PhD

April M. Bobenchik, PAD, D(ABMM) ‘Amy Mathers, MD, D(ABMN)

Shelley Campeon, PAD, D(ABMM) Tony Mazza. MD, FACP, FRCP(C)

Sharon K. Callen, BS, RAC ‘Michael Satin, MD, MS

Marcelo F. Galas “Audrey N. Schutz, MD, MPH, D(ABMM)

Howard Gold. MD, FIDSA Patricia. Summer, PRD, D(ABMN)

Romney M. Humpluies, PAD, D(ABMM) Pranita D. Tama, MD, MHS

Abstract

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CLINICAL AND

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STANDARDS
INSTITUTE"

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M100, sth ed

Copyright ®2020 Clinical and Laboratory Standards Insite, Except a stated below, any reproduction of
coment fiom a CLSI copyrighted standard, guideline, derivative produc, or other material requires
press wrlten consent rom CLSL All sights reserved. Interested pates may send permission requests to
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CLS hereby grants permission to each individual member or purchase to make a single reproduction of
this publican for use in its laboratory procedures manual ata singe site. To request permission to use
this publication in any other manner, e-mail permiscions(Zel org

Suggested Citation

CLS. Performance Standards for Animierobial Susceptbii Testing. 30th ed. CLSI supplement MIO.
Wayne, PA: Clinical and Laboratory Standards Insitute; 2020,

Previous Editions:
December 1986, December 1987, December 1991, December 1992, December 1994, December 1995,
January 1997, Jamary 1998, January 1999, January 2000, January 2001, January 2002, January 2003,
Jamary 2004, January 2005, January 2006, January 2007, Janvary 2008, January 2009, January 2010,
Sune 2010, Jane 2011, Jamary 2012, January 2013, Jamary 2014, January 2015, January 2016,
“Janay 2017, January 2018, January 2019

ISBN 978-1-68140-066.9 (Pin)
ISBN 978-1-68140-067-6 (Electronic)

ISSN 1558-6502 Print)

ISSN 2162-2914 (Electronic) Volume 40, Number 1

ee

M100, 0h ed

‘Committee Membership

‘Subcommittee on Antmlcroblal Susceptibility Testing
avi. Went, MD Ronan M Hap, FD,
rol Damos
igre oa Jon Met ee Dan
ane Lente FSA RN ann Me
go mae ES

Brad go, FD
See K. ln BS, RAC Center fr Die Cool ad
Dedman Colter Ine Merle Penta
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Ay Naben, MD, DAB)
Marco. Glas ‘niet of Vigia Medal Caer
Pan Ameca eth Organ USA
un

“Tay Maza MD, FAP, FRCHO)
Howard Gl MD, FIDSA Mat Sina Hoyt
Bella DescmenAedel Ceter Cada
Adknowedgment

Nov York enti ton

Auto N Sees. MD, MP
Dann
Ngoc

Pai Sims. PAD, DABA)
bus Hope cet of este,
Depart a Patsy

un

Prat Tan MD, AS
aus Hop Selo Meine,
Departa of Pear

CLSI and the Subcommittee on Antimicrobial Susceptibiliy Testing gratfily acknowledge the

following volunteers for thir important contributions to the revision of this document
AM Boba, PD, ABA Sly Cape PAD, (ABA)
Logan Acme Medicare Aesdenie Pape Ie

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M100, sth ed

Working Group on AST Breakpoints

Ce ae”
EN

Oregon Het an Sdence Untversey

eae Satin, DNS.
Sn Veran

tei arty

Working Group on Methods Application and Interpreta

"igs ober Wood tn Ne

Ban snr AD, AIN
‘Sims Hpk Shan o Mean,
Department Pl

Pan Amen Heath Organizan

Rene M Hopes PD,
Dans,

Arc Diagnosis, ne
ES

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Une of Vii Med Cor

vase args Fam.
Einen Mano Sa of mao,
Fuga e

Hat ot

Pace Capt D

Step 6 Jess, FD, DABA),
FOAM

sie Joleen, PD DADO,
Une of Maren Dale

Tor Kt, Pana
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Maye Cie

Simone sant
DA Ce e Drag Eat
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Lau D. Typ MD
Unie a ara vie
Mea Center

Ji Wane MD
Rae vey Pesan

Smit mo, roo. DN

Visine M Race MD
mn non

PAP. DSA

MD, DAB,

‘tom sharp. PAD. DABA).

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M100, 0h ed

Working Group on Methods Development a

Doig J Mardy, PAD
vel a Rochester Medel Center

Kater Sa BS

Working Group on Outreach

ter
Los Anges mn Department of
vn

x MCLS,MTASCH,

Andrey N. Schweiz, MD, MPH,
Dan

Co Charter

Mayo Game

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Stes Atos, PD, DARN
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Standardization

Kevin Ady. PD, ABI
‘Unc diol sta

‘an Ble, PAD, ABI,
aser

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A cn mo nam

Ae M oben FD, DAD
‘frp demi eel Cater

Angela Cen tas MD
US

‘Oregon Heath Sciences University

Tris Dingle PRD, D(ABMA)
Heap
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‘oneal AS Cane

‘Laura. Koh TAS)
Late Se e

A rc DIA

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Lan. Wests FD. DARN
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M100, sth ed

Working Group on Quality Control

Sharon K. Callen, BS, RAC Dana €. Dres, BS TASC
Co Guitar Inn Met ment
conan Cour, inc Merle Asoc ic

Ps x

Kia Grande Roche, AD
Maria Trace, BS MTASCR) FDA Cent for Dein nd

Co Chama Rodden Heat
Tec Cia cr tte CSA

Sage lade, CLS AMASCP)
Mica Duan BS FAM)
ermine Sera Ls Andes Canty Deno

Alec Ly Bsn. FAD, DABUN) Dad Loney, NOISE
isin Come Cure Melt Cases for Disease Cnt

Pasas. Cail MS, TASC)

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Fra

Des aft ad
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David Pass Be
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Moe LLC

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M100, 0h ed

Working Group on Text and Tables

AMM Bobenehik, PAD, TABNIND) Mary ane Faro. FD. MEL

Ce charter Mazcue Gen oil md
Hart don Shen

EN

Anden. Feel MLSASC)
Beam Die

ut À nl, MCLS,MTASCH,
FRA)
Lx Andes Coty Dept a

Melisa Jon, MTASCH CLS

‘icra Emma Ais, BA CMS, NT
Ms USA
ug! Je D, DAT
Univesity of Caen Rare
Duke Une Schoo of Medicine
Cina Laon Sond inte Megan L Tate, MA, ELS
Be L acne MEM. AIASCH) Cabe EM Jaks
Poet langer Era
Adknowedgment

aid ice MTASCI)
Mayo cine

Fini Ron MD, FD
‘Universo Sto Palo

Damage
Que Dias fen ise

amas "

Nano wa AAS,

Fay L Lars

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CLSI and the Subcommittee on Antimicrobial Suscepäbiity Testing gratefully acknowledge the
following former Working Group on Text and Tables members for their important consabutions to the

revision of is document

Peasy Kater, BS, ASCO) yan Lape BS, ASCSM
Maye cine BD Dinge Sans

Table of Contents

Contents

Abstract i
Committee Membership...

Overview of Changes xiv
Summary of CLSI Processes for Establishing Breakpoints and Quality Control Ranges xxvii

CLSI Reference Methods vs Commercial Methods and CLSI vs US Food and Drug Administration Breakpoints......

CLSI Breakpoint Additions/Revisions Since 2010...

CLSI Epidemiological Cutoff Value Additions/Revisions Since 2015 ..

CLSI Archived Resources ccoo
‘Subcommittee on Antimicrobial Susceptibility Testing Mission Statement soil

Instructions for Use of Tables...

References. 16

Table 1A. Suggested Groupings of Antimicrobial Agents Approved by the US Food and Drug Administration for Clinical Use That Should
Be Considered for Testing and Reporting on Nonfastidious Organisms by Microbiology Laboratories in the United States. 18

Table 1B. Suggested Groupings of Antimicrobial Agents Approved by the US Food and Drug Administration for Clinical Use That Should
Be Considered for Testing and Reporting on Fastidious Organisms by Microbiology Laboratories in the United States.

Table 1C. Suggested Groupings of Antimicrobial Agents Approved by the US Food and Drug Administration for Clinical Use That Should
Be Considered for Testing and Reporting on Anaerobic Organisms by Microbiology Laboratories in the United States i

Table 2A. Zone Diameter and MIC Breakpoints for Enterobacterales.....

Table 28-1. Zone Diameter and MIC Breakpoints for Pseudomonas aeruginosa

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Contents (Continued)

Table 2B-2. Zone Diameter and MIC Breakpoints for Acinetobacter spp. 46

Table 2B-3. Zone Diameter and MIC Breakpoints for Burkholderia cepacia complex...

Table 2B-1. Zone Diameter and MIC Breakpoints for Stenotrophomonas maltophili.

Table 28-5. MIC Breakpoints for Other Non-Enterobacterales.

Table 2C. Zone Diameter and MIC Breakpoints for Staphylococcus spp.

Table 2D. Zone Diameter and MIC Breakpoints for Enterococcus spp.

Table 2E. Zone Diameter and MIC Breakpoints for Haemophilus influenzae and Haemophilus parainfluenzae .

Table 2F, Zone Diameter and MIC Breakpoints for Neisseria gonorrhoeae

Table 2G. Zone Diameter and MIC Breakpoints for Streptococcus pneumoniae 82

Table 2H-1, Zone Diameter and MIC Breakpoints for Streptococcus spp. B-Hemolytic Group.

Table 2H-2. Zone Diameter and MIC Breakpoints for Streptococcus spp. Viridans Group 92

Table 21. Zone Diameter and MIC Breakpoints for Neisseria meningitidis... ..96

Table 25. MIC Breakpoints for Anaerobes 100

Table A. Tes or Extended Spectrum p-Loctanasesin Klebsiella pneumonie Klebsiella toc, Escherichia ol, and

Proteus mirabilis. a Er a a 104

Introduction to Tables 3B and 3C. Tests for Carbapenemases in Enterobacterales and Pseudomonas aeruginosa... 108

Table 3B. CarbaNP Test for Suspected Carbapenemase Production in Enterobacterales and Pseudomonas aeruginosa …….… =. 10 E

Table 3B-1. Modifications of Table 38 When Using MIC Breakpoints for Carbapenems Described in M100-S20 (January 2010)... 114 E
E

Table of Contents

Table of Contents

Contents (Continued)

‘Table 3C. Modified Carbapenem Inactivation Methods for Suspected Carbapenemase Production in Enterobacterales and Pseudomonas
aeruginosa .. ns e . ns ns

Table 3C-1. Modifications of Table 3C When Using MIC Breakpoints for Carbapenems Described in M100-520 January 2010)... 130
Table 3D. Tests for Colistin Resistance for Enterobacterales and Pseudomonas aeruginosa... is 132
Table 3E. Test for Detection of f-Lactamase Production in Staphylococcus spp. 138

Table 3F. Test for Detecting Methicillin (Oxacillin) Resistance in Staphylococcus spp.

Table 3G. Vancomycin Agar Screen for Staphylococcus aureus and Enterococcus spp. ...

Table 3H. Test for Detecting Inducible Clindamycin Resistance in Staphylococcus spp., Streptococcus pneumoniae, and Streptococcus spp.
P-Hemolytic Group 148

Table 31, Test for Detecting High-Level Mupirocin Resistance in Staphylococcus aureus.

Table 31. Test for Detecting High-Level Aminoglycoside Resistance in Enterococcus spp. (Includes Disk Diffusion) 154
Table 4-1. Disk Diffusion QC Ranges for Nonfastidious Organisms and Antimicrobial Agents Excluding P-Lactam Combination

Agents 156
Table 44-2. Disk Diffusion QC Ranges for Nonfastidious Organisms and B-Lactam Combination Agents. 160
Table 4B. Disk Diffusion QC Ranges for Fastidious Organisms 164
Table 4C. Disk Diffusion Reference Guide to QC Frequency... - 168
Table 4D. Disk Diffusion Troubleshooting Guide. 170
Table SA-1. MIC QC Ranges for Nonfastidious Organisms and Antimicrobial Agents Excluding B-Lactam Combination Agents... 14
Table SA-2. MIC QC Ranges for Nonfastidious Organisms and f-Lactam Combination Agents... 180

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Contents (Continued)

Table SB. MIC QC Ranges for Fastidious Organisms (Broth Dilution Methods) 184

x Table SC. MIC QC Ranges for Neisseria gonorrhoeae (Agar Dilution Method) … -188
à Table SD. MIC QC Ranges for Anaerobes (Agar Dilution Method)... 190
Table SE. MIC QC Ranges for Anaerobes (Broth Microdilution Method) cc 192

Table SF. MIC Reference Guide to QC Frequency ..

Table SG. MIC Troubleshooting Guide .

196

Table 6A. Solvents and Diluents for Preparing Stock Solutions of Antimicrobial Agents . 200

Table 6B. Preparing Stock Solutions for Antimicrobial Agents Provided With Activity Expressed as Units.

Table 6C. Preparing Solutions and Media Containing Combinations of Antimicrobial Agents 208

Table 7, Preparing Dilutions of Antimicrobial Agents to Be Used in Agar Dilution Susceptibility Tests...

Table 8A. Prepating Dilutions of Antimicrobial Agents to Be Used in Broth Dilution Susceptibility Tests.

Table 8B. Preparing Dilutions of Water-Insoluble Antimicrobial Agents to Be Used in Broth Dilution Susceptibility Tests...

Appendix A. Suggestions for Coniming Aninicrobil Sup Tes Roma end Organi Lin for Ages Approved by

the US Food and Drug Administration for Clinical Use..... 218

Appendix B. Intrinsic Resistance. 226

Appendix C. QC Strains for Antimicrobial Susceptibility Tests... .. 234

Appendix D. Anaerobe Cumulative Antibiogram. 240 E

Appendix E. Dosage Regimens Used to Establish Susceptible or Susceptible-Dose Dependent Breakpoints «u... 246 E
E

Table of Contents

Table of Contents

Contents (Continued)

Appendix F. Susceptible-Dose Dependent Interpretive Category...

Appendix G. Epidemiological Cutoff Values 251

Appendix H. Using Molecular Assays for Resistance Detection

Appendix 1. Cefiderocol Broth Preparation and Reading Broth Microdilution Minimal Inhibitory Concentration End Points 274
Glossary I (Part 1). f-Lactams: Class and Subclass Designations and Generic Names ...

Glossary I (Part 2). Non-f-Lactams: Class and Subclass Designations and Generic Names ..

Glossary II. Antimicrobial Agent Abbreviation(s), Route(s) of Administration, and Drug Class. 284
Glossary II. List of Identical Abbreviations Used for More Than One Antimicrobial Agent in US Diagnostic Products...
The Quality Management System Approach...
Related CLSI Reference Materials .

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Overview of Changes

M100, 30th ed. replaces the previous edition of the supplement, M100, 29th ed, published in 2019. The major changes in M100, 30th ed, are
listed below. Other minor or editorial changes were made to the general formatting and to some of the table footnotes and comments. Changes to
the tables since the previous edition appear in boldface type. The following are additions or changes unless otherwise noted as a “deletion.”

Users of M100, 30th ed. should note recent and new formatting changes to Tables 2, including:

+ Intermediate ranges denoted with a ©” for the applicable antimicrobial agents in the drug groups in Tables 2 are based on the known
ability of these agents to concentrate in the urine; some agents may also have the potential to concentrate at other anatomical sites
Ge, epithelial lining).

M100 is updated and reviewed annually as new da
discouraged.

and new agents become available. Use of outdated documents is strongly

General

Throughout the document | Replaced:
+ *Coagulase-negative staphy locoeei (CoNS)" with “other Staphylococcus spp.
+ Theterm “infection control” with “infection prevention”.

Updated:
‘© Genera formerly included in the family Enterobacteriaceae reorganized to an order (Enterobacterales) containing
seven families: Buchiciaceae, Enterobacteriaceae, Erwiniaceae, Hafniaceae, Morganellaceae, Pectobacteriaceae,
Yersiniacece*
Nomenclature for Salmonella Typhi to Salmonella enterica ser. Typhi
‘Nomenclature for Salmonella Paraty phi to Salmonella enterica set. Paratyphi

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‘General (Continued)
“CLSI Breakpoint ‘Added:
Additions /Revisions © Cefiderocol disk diffusion breakpoints for Enterobacterales (p. xix), Pseudomonas aeruginosa (p. 0%),
Since 2010 Acinetobacter spp. (p. xx), and Stenotrophomonas maltophilia (p. x)
‘© Colistin (p. xix) and polymyxin B (p. xxx) minimal inhibitory concentration (MIC) breakpoints for Enterobacterales
+ Daptomycin MIC breakpoints for Enterococcus faeciuun only (originally included in the March 2019
re-released version of M100, 29th ed.) (p. so)
Revi
+ Colistin and polymyxin B MIC breakpoints for P. aeruginosa and Acinetobacter spp. (p. xx)
+ Daptomycin MIC breakpoints for Enterococcus spp. other than E faecium (originally included in the March 2019
re-released version of M100, 29th ed.) (p. xxx)
Reinstated:
© Norfloxacin breakpoints deleted from M100, 29th ed. (pp. xxix-s00xi)
CLSI Epidemiological Cutoff | Deleted:

Value Additions/Revisions | + Colistin epidemiological cutoff value (ECV) (Enterobacterales; now assigned a breakpoint in Table 2A)
Since 2015
CLSI Archived Resources ‘Added:

+ Link to the archived table for QC ranges eliminated from M100 since 2010 (p. xxi)
+ Link to the archived table for BCVs eliminated from M100 since 2010 (p. xxxii)

Instructions for Use of Tables
IL. Breakpoint and Revised:

Interpretive Category + Breakpoint examples for the nonsusceptible interpretive category (p. 4)
Definitions + Susceptible-dose dependent (SDD) category definition (p. 4)

+ Intermediate category definition (p. 5)

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Overview of Changes (Continued)

Instructions for Use of Tables (Continued)
VIII Routine, Supplemental, | Supplemental Tests (Optional) table
Screening, Surrogate Agent, Added:
and Equivalent Agent Testing | + Colistin agar test (p. 11)
to Determine Susceptibility | e _Colistin broth disk elution (p. 11)
O ‘Supplemental Tests (Required and Optional) tables
Antimicrobial Agents Revised:
+ References to appropriate Tables 3 (pp. 10-11)
‘Screening Tests table
Revis
+ References to appropriate Tables 3 (p. 12)
‘Surrogate Agent Tests table
Clarified:
+ Cefoxiin test description for specific Staphylococcus spp. (. 12)
Revise
+ _ Reference to appropriate Table 3 (p. 12)
‘Examples of Equivalent Agent Tests table
Added:
+ Colistin and polymyxin B for Enterobacterales, P. aeruginosa, and Acinetobacter baumaæmi complex (p. 13)
X. Abbreviations and ‘Added:
‘Acronyms + CAT (colistin agar test) (p. 14)

‘+ CBDE (colistin broth disk elution) (p. 14)
‘© ICR (inducible clindamycin resistance) (p. 14)
© _ MH-F agar (Mueller-Hinton fastidious agar) (p. 14)

Revised:
+ MRS (methicillin [oxacilin]-resitant staphylococci) (p. 15)

+ MRSA (methicillin [oxacillin-resistant Staphnlococcus aureus) (p. 15)
© NAD G-nicotinamide adenine dinucleotide) (p. 15)

Deleted:
+ CONS (coagulase-negative staphylococci)
+ KPC (Klebsiella pneumoniae carbapenemase)
© NDM (New Delhi metallo-B-Jactamase)

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Overview of Changes (Continued)
[——Section/Table_ JE _Change(s)_ |
Tables 1. Suggested Groupings of Antimicrobial Agents Approved by the US Food and Drug Administration for Clinical Use That

‘Should Be Considered for Testing and Reporting by Microbiology Laboratories in the United States
AU Tables 1 Reformatted:
+ Tables to clarify criteria for inclusion in each group
Replaced:
+ TestReport Group column and descriptions for Groups A, B, C, and U with expanded descriptions
(as listed in the Instructions for Use of Tables, Section IC)
Table 1A. Nonfastidious Added:
Organisms ‘+ Footnote for Group B directing users to the Instructions for Use of Tables for examples of when a Group B agent
might be reported (p. 18)
Clarified for Staphylococcus spp-:
+_ Oxacilin footnote regarding testing methods (p 18)
Relocated from Group B to Group A (in the same box as trimethoprim-sulfamethoxazole) for S. malophilia:
+ Levofloxacin(p. 19)
+ Minocycline (p. 19)

Table IB. Fastidious Added:
Organisms ‘© Footnote for Group B directing users tothe Instructions for Use of Tables for examples of when a Group B agent
might be reported (p. 24)
Clarified for Streptococeus spp.

+ Footnote regarding inducible clindamycin resistance (CR) reporting (p. 24)

Tables 2. Zone Diameter and/or MIC Breakpoints

General Added:

+ _ Reference for the M02 Disk Diffision Reading Guide to appropriate tables

Table 2A. Enterobacterales | Added:

+ Salmonella enterica ser. Typhi routine QC strain recommendations for azithromycin (p. 32)

+ General comment explaining the use of the *”;” with intermediate breakpoints for appropriate antimicrobial agents
@.32)

‘© Cefiderocol testing requirements (p. 32), reference (p. 32), and investigational disk diffusion breakpoints (p. 36)

® Colistin and polymyxin B MIC breakpoints, waming, reporting comments, and reference (p. 38)

+ _1/ designation for B-lactams (p. 33), aminoglycosides (p. 38), and fluoroquinolones (pp. 39-40)

Clarified:

+ Ceftazidime-avibactam reporting comment (p. 33)

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Tae
+ Norfloxacin disk diffusion and MIC breakpoints and reporting comment deleted from M100, 29th ed. (p. 39)

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Tables 2. (Continued)

Table 2B-1. Pseudomonas
aeruginosa

‘Added:

© General comment explaining the use of the”. with intermediate breakp oints for appropriate antimicrobial agents
0.12

+ Cefiderocol testing requirements (p. 42), reference (p. 42), and investigational disk diffusion breakpoints (p. 43)

+ 1 designation for B-lactams (p. 43), aminoglycosides (p. 45), and fluoroquinolones (p. 45)

Revised:
+ _Colistin and polymyxin B MIC breakpoints, wa

reporting comments, and reference (p. 44)

Reinstate
+ _Norflosacin disk diffusion and MIC breakpoints and reporting comment deleted from M100, 29th ed (p. 45)

Table 282. Acinetobacter spp.

“Added:
+ Cefiderocol testing requirements (p. 46), and reference (p. 46), and investigational disk diffusion breakpoints (p. 47)

Revised:
‘© Colistin and polymyxin B MIC breakpoints, waming, reporting comments, and reference (p. 48)

Table 2B-4, Stenotrophomonas
maltophilia

Added:
+ Cefiderocol testing requirements (p.52), reference (p. 2), and investigational disk diffusion breakpoints (p. $3)

Revised:
© _ Testireport group for

cycline and levofloxacin from B to A (p. 53)

Table 285. Other
Non-Enterobacterales

Clarified:
+ _ General comment regarding the species designated as non-Enterobacterales (p. 54)

Reinstated:
+ Norfloxacin MIC breakpoints and reporting comment deleted from M100, 29th ed. (p. 55)

Table 2C. Staphplococens spp.

Added:
© Recommendation for selecting QC strains for routine QC of B-lactam combination agents (p. 58)

Clarified:
© Oxacilli reporting for other Staphylococcus spp. with MICs 0.5-2 pg/mL (p. 62)
© ICR reporting comment (p. 65)

Revised:

+ Methods for Detection of Methicillin (Oxacillin)-Resistant Staphylococcus spp. table in general
comment (5) to include incubation times for detecting methicillin (oxacilin resistance (p. 59)

Reinstated:
+ Noriloxaci

jon and MIC breakpoints and reporting comment deleted from M1 00, 29th ed. (p. 64)

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Tables 2. (Continued)
Table 2D. Enterococcus spp. | Added:
‘Recommendation for selecting QC strains for routine QC of B-lactam combination agents (p. 68)
+ General comment explaining the use of the “with intermediate breakpoints for appropriate antimicrobial agents
@. 68)
+ Daptomycin MIC breakpoints (SDD and resistant only) and dosage regimen for E. faeciu only (originally included
the March 2019 re-released version of M100, 29th ed.) (p. 70)
+ Daptomycin intermediate MIC breakpoint and dosage regimen for Enferococcus spp. other than E faecium
(originally included in the March 2019 re-released version of M100, 29h ed) (p. 70)
+ _I? designation for fluoroquinolones and oxazolidinones (p. 71)
Revised:
+ Daptomycin susceptible MIC breakpoint for Enterococcus spp. other than E faecium (originally included in the
March 2019 re-released version of M100, 29h ed.) (p. 70)
Reinstated:
+ Norfloxacin disk diffusion and MIC breakpoints and reporting comment deleted from M100, 29th ed. (p. 71)
Table 2G. Streptococcus Added:
pneumoniae ‘© Mueller-Hinton fastidious agar (MH-F agar) as an altemative for disk diffusion testing (p. 82)
+ _ Reporting comment for oral cefuroxime (p. 84)
Clarified:
ICR reporting comment (p. 86)
Table 2H.1. Streptococcus spp. | Clarified:
B-Hemolytic Group + Enythromyein reporting comment (p. 90)
+ _ICR reporting comment (p. 91)
Tables 3. Specialized Resistance Testing (NOTE: Tables following 3C were renumbered to accommodate addition of the new Table 3D.)
Table 3A. Tests for Extended- | Revised:

Spectrum f-Lactamases in | Aztreonam disk diffusion QC range for Klebsiella pneumoniae ATCC? 700603 for the extended-spectrum
Klebsiella pneumoniae, P-lactamase (ESBL) test (p. 106)
Klebsiella oxytoca, Escherichia

(coli, and Proteus mirabilis
Table 3B. CarbaNP Test for | Added:
‘Suspected Carbapenemase + _New references (p. 110)

Production in Revised:
Enterobacterales and + NOTE 1 regarding ability to detect OXA-48-ke producers (p. 113)
Pseudomonas aeruginosa

Po Oe DOUX

Tables 3. Continued)

Table 3C. Modified ‘Added:
Carbapenem Inactivation | + Newreferences (p. 118)

Methods for Suspected

Carbapenemase Production in

Enterobacterales and

Pseudomonas aeruginosa

Table 3D. Tests for ‘Added:

Colistin Resistance for + Colistin broth disk elution (CBDE) procedure (pp. 132-134), QC recommendations (p. 134), and associated figures
Enterobacterales and 6.139

Pseudomonas aeruginosa + Colistin agar test (CAT) procedure (pp. 132-134), QC recommendations (p. 134), and associated figures (p. 137)
(new table)

Table 3F. Detecting ‘Added:

Methicillin (Oxacilin) + Options and respective procedures for detecting mecd-mediated resistance using cefositin or oxacillin with
Resistance in Staphylococcus disk diffusion, broth microdilution, or agar dilation methods (pp. 142-143)

spp. (formerly Table 3E) ‘+ QC strains recommended for when various methods are used for detecting methicillin (oxacillin} resistance (p. 144)
Table 3H. Test for Detecting | Clarified:

Inducible Clindamycin ‘© Organism groups to be tested (pp. 148-149)

Resistance in Staphylococeus | + ICR reporting comments (p. 149)

«pp. Streptococcus

Pneumoniae, and Streptococeus

spp. P-Hemolytic Group
(formerly Table 3G)

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Overview of Changes (Continued)

Tables 4. Disk Diffusion QC Ranges and Associated Tables
Table 4A-1. Disk Diffusion | Added:

QC Ranges for Nonfastidious | — Sulopenem disk diffusion QC ranges for Escherichia coli ATCC® 25922 (p. 158)

Organisms and Antimicrobial | ¢ Tedizolid disk diffusion QC ranges for E. faecalis ATCC? 29212 as a supplemental QC strain (p. 158)
Agents Excluding P-Lactam | Revised:

‘Combination Agents i n QC range for E. coli ATCC® 25922 (p. 157)

content and QC ranges for $. aureus ATCC® 25923 (p. 158)

Reinstated:
+ _Norfloxacin QC ranges forall QC strains deleted from M100, 29th ed. (p. 158)

Table 442. Disk Diffusion | Add

QC Ranges for Nonfastidious | © Guidance on reading cefipime QC results for Æ coli NCTC 13353 and A. baume NCTC 13304 (p. 160)
‘Organisms and p-Lactam + Guidance on reading meropenem QC results for all QC organisms (p. 160)

‘Combination Agents «Disk diffusion QC ranges for:

Ecol ATCC 28922
aeruginosa ATCC® 27853

Ecol ATCO? 38218

E pneumoniae ATCC 700603
coli NCTC 13383

E preunontae ATCC BAA TON
A Baumann NCTC 13304 x

Table 4B. Disk Diffusion Added:
QC Ranges for Fastidious + MELF agar for S pneumoniae only to the disk diffusion testing conditions table located in the column for
Organisms streptococci and Neisseria meningitidis (p. 166)

: Revised:

: + Tedizolid disk content and QC ranges for Streptococcus pneumoniae ATCC? 49619 (p. 165)

A Reinstated:

© Norfloxacin QC ranges for all QC strains deleted from M100, 29th ed. (p. 165)
Table 4D. Disk Diffusion “Added:
‘Troubleshooting Guide + _Tedizolid troubleshooting information and guidance on reading plates (photographs) (pp. 171, 173)

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Overview of changes

El Overview of Changes (Continued) E
jam IN ANA III IA Af E
Tables 5, MIC QC Ranges and Associated Tables El
: Table 5A-1.MIC QC anges | Added:
a for Nonfastidious Organisms ba
+ and Antimicrobial Agents
‘Excluding B-Lactam
Combination Agents
Taro MES PAS x x x
E faecalis ATOC? 29212 x x x
+ Footnote regarding exebacase QC ranges (p. 175)
Revised:
+ Eravacycline QC range for E, coli ATCC® 25922 (p. 175)
Reinstated:
+ Norfloxacin QC ranges deleted from M100, 29th ed. (p. 176)
Delete:
+ _ Plazomicin QC range for E. faecalis ATCC® 29212
Table 5A2.MIC QC Ranges | Added:
for Nonfastidious Organisms: »__MIC QC ranges for:
: and B-Lactam Combination
: Agents
: E. coli ATCC® 25922 x x. x x
P aeruginosa ATCC® 27853 x x
B Ecol ATCC? 39018 x x
Ee pneumoniae ATCC 70080 x x x
Ecol NETC à x x
E preumónias ATCC BATS x
E pneunonae ATC DAR IEA
4 Baumann NCTC 13304 x x x
Revised:
+ MIC QC range for imipenem-relebactam and X pneumoniae ATCC? BAA-2814™ (p. 181)

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Overview of. mess ¿eones

Tables 5. (Continued)

Table SB. MIC QC Ranges for
Fastidious Organisms (Broth,
Dilution Methods)

E pneumoniae ATCC® 49619 x x
Reinstated:

+ Norfloxacin QC ranges deleted from M100, 29th ed. (p. 185)

Table SC. MIC QC Ranges for | Added:

Neisseriagonorrhoeae (Agar | © Zoliflodacin MIC QC ranges for N. gonorrhoeae ATCC? 49226 (p. 188)

Dilution Method)
Tables 6. Preparing Antimicrobial Agent Stock Solutions
Table 6A. Solvents and ‘Added:
Diluents for Preparing Stock | e Footnote regarding confirming the appropriate solvents and diluents for antimicrobi
Solutions of Antimicrobial ‘manufacturer (p. 200)
Agents + Solvent and diluent information for:
= Durlobactam
= Enmetazobactam
= Bxebacase
= Ozenoxacin
— Taniborbactam
—__Zoliflodacin
Reinstated:

+ Norfloxacin solvent and diluent information deleted from M100, 29th ed.
Table 6C. Preparing Solutions | Added preparation instructions for:

: and Media Containing + Cefepime-enmetazobactam
: ‘Combinations of + Cefepimetaniborbactam
: Antimicrobial Agents + Sulbactam-durlobactam

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Tests

[Appendixes
“Appendix A. Suggestions for | Added:
Confirming Antimicrobial | © Colunn for antimicrobial class or subclass
Susceptibility Test Results and | © Clarifying footnotes (pp. 218-219, 221)
‘Organism Identification for |» Newer agents hat have US Food and Drug Administration approval (eg, ceftazidime-avibactam, ceftolazane-
Agents Approved by tazobactam, meropenem-vaborbactam, plazomicin)
he US Food and Drug + NewECvs
Administration for + Footnote regarding variations in vancomycin MICs for S aureus
Clinical Use (entire table Bande craie vl ele MiGs for À crus 0.220
revise) + Title changed from “Suggestions for Confirming Resistant, Intermediate, or Nonsusceptible Antimicrobial
Susceptibility Test Results and Organism Identification” to “Suggestions for Confirming Antimicrobial Susceptibility
Test Results and Organism Identification for Agents Approved by the US Food and Drug Administration for Clinical
Use”
Category action step definitions (p. 218)
Order of the antimicrobial agents to be more consistent with Tables 2
Categories for:
~ Colistin (Enterobacterales, Acinetobacter baumannii complex, P. aeruginosa) (pp. 218-219)
— Any carbapenem (A. Aaumenni complex) (p. 219)
- Trimethoprim-sulfameihoxazole (S maltophilia) (p. 219)
= Vancomyein (S. aurens) (p. 221)
Grouped classes of antimicrobial agents together and added categories for:
# Azithromycin (Salmonella and Shigella; N. gonorrhoeae) (pp. 219, 220)
+ Cefazidime-avibactam (Enterobacterales)(p. 218)
+ Ceftolozane-tazobactam (P. aeruginosa) (p. 219)
+ Meropenem-vaborbactam (Enterobacterales) (p. 218)
+ _Plazomicin (select Enterobacterales) (p 218)
Appendix B. Intrinsic Added:
Resistance «__ Clostridioides spp. to section BS, Anaerobic Gram-Positive Bacili(p. 232)
“Appendix C. QC Strains for | Added:
Antimicrobial Susceptibility | + E coli AR Bank #0349 (p.235)

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Overview of. mess son nue)

‘Appendixes (Continued)

‘Appendix E. Dosage Regimens | Added:

Used to Establish Susceptible | e Daptomycin SDD MIC breakpoint and dosage regimen for Z. faecitun only (p. 248)

or Susceptible-Dose + Daptomycin dosage regimen for Enterococcus spp. other than E. fteciua (p. 248)

Dependent Breakpoints + Colistin and/or polymyxin B dosage and treatment regimen reference for Enterobacterales, P. aeruginosa,
and Acinetobacter spp. (pp. 246-247)

Revised:

© Daptomycin susceptible MIC breakpoint for Enterococcus spp. other than E. faecium (p. 248)

Deleted:

+ Meropenem-vaborbactam for P. aeruginosa; no breakpoints for this antimicrobial agent and organism.

+ Colistin dosage regimen for P. aeruginosa and Acinetobacter spp.

“Appendix G. Epidemiological | Revised:

Cutoff Values ‘+ Definition for wild-type and non-wild-type in section GA, Defining Epidemiological Cutoff Values (p. 254)
Deleted
+ Colistin from Table G1 (ECVs for Enterobacterales) in section G2, Epidemiological Cutoff Value Tabl

now assigned a breakpoint in Table 2A

“Appendix I, Cefiderocol Broth | Added:
Preparation and Reading ‘* Instructions for preparing zine stock solution and iron-depleted cation-adjusted Mueller-Hinton broth (p. 274-275)
Broth Microdilution Minimal | + Instructions for reading results and determining end points for broth microdilution MIC tests (p. 275)

Inhibitory Concentration End | Example photographs showing nontrailng and trailing MIC end points (p. 276)

Points (new appendix)

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Overview of changes

Overview of Changes (Continued)

Section/Table Change(s)

‘Glossaries

Y (Part D. -Lactams: Class] Added:

and Subelass Designations | + Cefepime-enmetazobactam as af-nctam combination agent

and Generie Names + Cefepimetaniborbactam as a lactam combination agent
+ _Sulbactam-durlobactam as a B-lactam combination agent

T (Part 2): Non-P-Lactams: | Added:

Class and Subclass + Exebacase as an antistaphylococeal lysin
Designations and Generic | « Ozenoxacin as a fluoroquinolone
Names +_Zolflodacin as a spiropyrimidinetrione
“Moved:
‘+ Ramoplanin to its own row as alipoglycodepsipeptide
Reinstated:
+ _Norfloxacin as a fluoroquinolone deleted from M100, 29th ed.
MI. Antimicrobial Agent | Added:

Abbreviation(s), Route(s) of
‘Administration, and Drug
Class

Cefepime-enmetazobactam as a f-lactam combination agent
Cefepime-taniborbactam as a B-lactam combination agent
Exebacase as an antistaphylococcal fysin

Ozenoxaein as a fluoroquinolone

Sulbactam-durlobactam as a B-lactam combination agent
Zoliflodacin as a spiropyrimidinetrione

Reinstated:
+ Norfloxacin as a fluoroquinolone deleted from M100, 29th ed.

‘Abbweviaion: ATCC®, American Type Culture Collection,
* ATCC? sa register trademark ofthe American Type Culture Colleton.

NOTE: The content of this document is supported by the CLSI consensus process and does not necessarily reflect the views of any single
individual or organization.

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Summary of CLSI Processes for Establishing Breakpoints and Quality Control Ranges

‘The Clinical and Laboratory Standards Institute (CLSI) is an intemational, voluntary, not-for-profit, interdisciplinary, standards-developing, and
educational organization accredited by the American National Standards Institute that develops and promotes the use of consensus-developed
standards and guidelines within the health care community. These consensus standards and guidelines are developed in an open and consensus-
seeking forum to cover critical areas of diagnostic testing and patient health care. CLSI is open to anyone or any organization that has an interest
in diagnostic testing and patient care. Information about CLSI can be found at www .clsi org,

The CLSI Subcommittee on Antimicrobial Susceptibility Testing reviews data from a variety of sources and studies (eg, in vitro,
pharmacokinetics-pharmacodynamics, and clinical studies) to establish antimicrobial susceptibility test methods, breakpoints, and QC parameters,
‘The details of the data necessary to establish breakpoints, QC parameters, and how the data are presented for evaluation are described in CLSI
document M23.°

Over time, a microorganism's susceptibility to an antimicrobial agent may decrease, resulting in a lack of clinical efficacy and/or safety. In
addition, microbiological methods and QC parameters may be refined to ensure more accurate and better perfomance of susceptibility test
methods. Because of these types of changes, CLSI continually monitors and updates information in its documents. Although CLSI standards and
guidelines are developed using the most current information available at the time, the field of science and medicine is always changing; therefore,
standards and guidelines should be used in conjunction with clinical judgment, current knowledge, and clinically relevant laboratory test results to
guide patient treatment

Additional information, updates, and changes in this document are found in the meeting summary minutes of the Subcommittee on Antimicrobial
Susceptibility Testing at https://clsi.org/meetings/ast-file-resources).

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CLSI Reference Methods vs Commercial Methods and CLSI vs US Food and Drug Administration Breakpoints

It is important for users of M02, M07,* and M100 to recognize that the standard methods described in CLSI documents are reference methods.
These methods may be used for routine antimicrobial susceptibility testing of patient isolates, for evaluating commercial devices that will be
used in medical laboratories, or by drug or device manufacturers for testing new agents or systems. Results generated by reference methods,
such as those included in CLSI documents, may be used by regulatory authorities to evaluate the performance of commercial susceptibility
testing devices as part of the approval process. Clearance by a regulatory authority indicates the commercial susceptibility testing device
provides susceptibility results that are substantially equivalent to results generated using reference methods for the organisms and antimicrobial
agents described in the device manufacturer's approved package insert.

CLSI breakpoints may differ from those approved by various regulatory authorities for many reasons, including use of different databases,
differences in data interpretation, differences in doses used in different parts of the world, and public health policies. Differences also exist
because CLSI proactively evaluates the need for changing breakpoints. The reasons why breakpoints may change and the manner in which
CLSI evaluates data and determines breakpoints are outlined in CLSI document M23.*

Following a decision by CLSI to change an existing breakpoint, regulatory authorities may also review data to determine how changing
breakpoints may affect the safety and effectiveness of the antimicrobial agent for the approved indications. If the regulatory authority changes
breakpoints, commercial device manufacturers may have to conduct a clinical trial, submit the data to the regulatory authority, and await review
and approval. For these reasons, a delay of one or more years may be needed if a breakpoint and interpretive category change is to be
implemented by a device manufacturer. In the United States, it is acceptable for laboratories that use US Food and Drug Administration (FD A)
cleared susceptibility testing devices to use existing FDA breakpoints. Either FDA or CLSI susceptibility breakpoints are acceptable to
laboratory accrediting organizations in the United States. Policies in other countries may vary. Each laboratory should check with the
‘manufacturer of its antimicrobial susceptibility test system for additional infomation on the breakpoints and interpretive categories used in its
system’s software.

Following discussions with appropriate stakeholders (eg, infectious diseases and pharmacy practitioners, the pharmacy and therapeutics and
infection prevention committees of the medical staff, and the antimicrobial stewardship team), newly approved or revised breakpoints may be
implemented by laboratories. Following verification, CLSI disk diffusion test breakpoints may be implemented as soon as they are published in
M100. If a device includes antimicrobial test concentrations sufficient to allow interpretation of susceptibility and resistance to an agent using
the CLSI breakpoints, a laboratory could choose to, after appropriate verification, interpret and report results using CLSI breakpoints,

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CLSI Breakpoint Additions/Revisions Since 2010
Date of Addition/Revision"
Antimicrobial Agent (M100 edition) Comments
Enterobacterales
‘Azithromycin — enterica ser. Typhi only January 2015 (100-825)
Aztreonam January 2010 (M100-S 20)
Cefazolin January 2010 (M100-820) Breakpoinis were revised twice since 2010.
January 2011 (M100-S21)
2 January 2014 (M100-S24)_ Breakpoints were added to predict results for cefazolin when
A January 2016 (MIOOS, 26th ed) _ | cefazolin is used far therapy of uncomplicated UTIs.
1 Cefepime January 2014 (M100-S24)
: Cefiderocol January 2019 (MIO, 28th ed) | NPBP
January 2020 (M100, 30th ed) — | Disk diffusion breakpoints were added.
: Cefotaxime January 2010 (M100-S20)
4 Ceftaroline January 2013 (M100-S23) NPBP_
: Ceftazidime January 2010 (M100-S20)
Ceftazidime-avibactam January 2018 (M100, 28th ed.) NPBP_
Ceftizoxime January 2010 (M100-S20)
Ceftolozane-tazobactam January 2016 (M1008, 26th ed.) NPBP_
January 2018 (M100, 28th ed.) Disk diffusion breakpoints were added.
January 2010 (M100-S20)
January 2019 (M100, 29th ed. Disk diffusion and MIC breakpoints were revised.
: — Salmonella spp. January 2012 (M100-S22) Anatomical site-specific breakpoint recommendations were
À Gncluding S enterica ser. Typhi) removed in 2013
q Colistin January 2020 (M100, 30th ed) — | NPBP, previously assigned an ECV
Doripenem June 2010 (M11 00-820-U) NPBP
2 Ertapenem June 2010 (M100-S20-U) Breakpoints were revised twice since 2010.
B January 2012 (M100-822)
: Timipenem June 2010 (M100-820-U)
Levofloxaci “January 2019 (M100, 25th ed) — | Disk difusion and MIC breakpoints were revised.
Levofloxacin ~ Salmonella spp. January 2013 (M100-823)
À (including $ enterica ser. Typhi)
: Meropenem June 2010 (M100-520:0)
i Meropenem-vaborbactam. January 2019 (M100, 29th ed) | NPBP
‘Norfloxacin January 2020 (M100, 30th ed) — | Reinstated breakpoints deleted from M100, 25th ed a
: IS
: Ea

xxx

CLSI Breakpoint Additions/Revisions Since 2010 (Continued)

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Antimicrobial Agent

‘Date of Addition/Revision”
(41100 edition)

Enterobacterales (Continued)

‘Ofloxacin — Salmonella spp.
including $: enterica ser. Typhi)

June 2013 (M100-523)

Pefloxacin - Salmonella spp.
(including $: enterica ser. Typhi)

Jamuary 2015 (1100-835)

‘Surrogate test for ciprofloxacin was added

Polymyxin B January 2020 (7100, 30th ed) | NPBP
‘Pseudomonas aeruginosa
Cefiderocol January 2019 (M100, 29th ed) _TNPBP

January 2020 (M100, 30th ed.) _| Disk diffusion breakpoints were added.
Ceftazidime-avibactam January 2018 (M100, 28h ed.) | NPBP
Ciproflosac January 2019 (M100, 20h ed) | Disk diffusion and MIC breakp oints were revised
Colistin January 2017 (M100, 27h ed) — | MIC breakpoints were revised

January 2020 (M100, 30th ed.)

MIC breakpoints were revised.

Doripenan. January 2012 (M100-822)

Imipenem January 2012 (M100-822)

Levofloxaci January 2019 (M100, 29th ed) | Disk diffusion and MIC breakpoints were revised
Meropenem January 2012 (100-8.

‘Norfloxacin January 2020 (M100, 30th ed.) — | Reinstated breakpoints deleted from M100, 29th ed.
Piperacill January 2012 (M100-8:

Piperacilin-tazobactam January 2012 (MI00-522)
Polymyxin B “January 2020 (MI00, 30th ed) | MIC breakpoints were revised.
Tieareillin January 2012 (M100-$22)
Ticareilin-clavulanate January 2012 (M100-822)
“Acinetobacter spp.
Cefiderocol January 2019 (M100, 29th ed) _TNPBP

January 2020 (M100, 30th ed.) | Disk diffusion breakpoints were added.
Colistin January 2020 (M100, 30th ed) — | MIC breakpoints were revised.
Doripanen January 2014 (100-524)
Imipenem January 2014 (M100-824)
Meropenem January 2014 (M100.824)
Polymyxin B January 2020 (M100, 30th ed) — | MIC breakpoints were revised.

‘maltophia

Cefiderocol January 2019 (M100, 29th ed) | NPBP

‘January 2020 (M100, 30th ed.)

Disk diffusion breakpoints were added.

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CLSI Breakpoint Additions/Revisions Since 2010 (Continued)
Date of Addition/Revision™
Antimicrobial Agent (M1100 edition) Comments

‘Other Non-Enterobacterales

‘Norfloxacin January 2020 (M100, 30th ed.) — | Reinstated breakpoints deleted from M100, 29th ed.

‘Staphylococcus spp.

Charlie January 2013 (1100-923) NPBP
a January 2019 (M100, 29th ed.) | Disk diffusion and MIC breakpoints were revised to include an
SDD interpretive category.
E Dalbavancin January 2018 (M100, 28th ed) — | NPBP
‘Norfloxacin January 2020 (M100, 30th ed.) — | Reinstated breakpoints deleted from M100, 25th ed.
‘Oritavancin January 2016 (MIOOS, 26th ed) | NPBP

Tedizolid January 2016 (MIOOS, 26th ed) | NPBP

Telavancin January 2016 (MI00S, 26th ed.) | NPBP

Enterococcus spp.

Dalbavancin January 2018 (M100, 28th ed.) | NPBP

Daptomycin January 2019 (M100, 29th ed) | MIC breakpoints for E faecium only were added.
: January 2020 (M100, 30th ed.) — | MIC breakpoints for Enteracoceus spp. other than E faecium
A were revised.
À ‘Norfloxacin January 2020 (M100, 30th ed) _| Reinstated breakpoints deleted from MI00, 29th ed.
à ‘Oritavancin January 2016 (M100S, 26th ed.) | NPBP

Tedizolid January 2016 (M1008. 26th ed) | NPBP
A Telavancin January 2016 (M100$, 26th ed) | NPBP
: | Haemophilus influenzae and Haemophilus parainfluenzae
2 Ceñaroline | January 2013 (M100-$23) NPBP

| Neisseria gonorrhoeae
‘Azithromycin [ianuary 2019 041100. 25th ed) [ NPBP. previously assigned an ECV
¡Sireriscoccas puma}

Caroline January 2013 (M100-523) NPBP

Dosyeyeline January 2013 (MI00-523) NPBP.

Tetracycline January 2013 (M100-S23)
: | Streptococcus spp. B-Hemolytic Group
Ceftaroline January 2013 (M100-823) NPBP
E Dalbavancin January 2018 (M100, 28th ed) _ | NPBP

‘Oritavancin January 2016 (M100S, 26th ed.) | NPBP E
: Telavancio January 2016 (MIOOS, 26th ed) | NPBP 3
: E

max

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: CLSI Breakpoint Additions/Revisions Since 2010 (Continued) E
: Date of Addition Revision” E
i Antimicrobial Agent (1100 edition) Comments 3
À ‘Streptococcus spp. Viridans Group E
a Ceftolozane-tazobaetam January 2016 (MIOOS, 26th ed) | NPBP 2
À Dalbavancin January 2018 (M100, 28th ed) | NPBP
: ‘Oritavancin January 2016 (M100S, 26th ed.) | NPBP
E Tedizolid January 2016 (MIOOS, 26th ed) | NPBP

Telavancin [January 2016 (M100S. 26th ed) — | NPBP

Anaerobes.

Piperacillin-tazobactam [January 2017 (M100, 28th ed. [MIC breakpoints were revised.

“Previous breakpoints can be found in the edition of M00 that precedes the document listed here, eg, previous breakpoints for aztreonam are litedin MIDO-SI9 Canary 2009).
Abbreviations: ECV, epidemiological cof value; MIC, minimal inhibitory concentration; NPBP, no previous breakpoint existed, SDD, susceptible dose dependent, UTE, winary
act infection.

CLSI Epidemiological Cutoff Value Additions/Revisions Since 2015

Date of AdditiowRevision
Antimicrobial Agent (M1100 edition) Comments
Enterobacterales
Azithromycin January 2016 (M1008, 26th ed) For use with Shigella flexneri and Shigella sonnei
‘Anaerobes:
‘Vancomycin January 2015 (M100-825} For use with Cutibacterium (Formerly Propionibacterium) acnes.
CLSI Archived Resources
Resource. Web Address for Archived Table

Breakpoints that have been eli
relocated to the CLSI website
‘Methods that have been eliminated from M100 have been relocated to the | hitps:/elsi orgimedia/1$99/_ml00_archived_methods table pdt
CLSI website.
QC ranges that have been eliminated from M100 since 2010 have | hitps:/elsi.org/media/3202/_m100_archived_qc_table-pat
een relocated to the CLSI website.

ECVs that have been replaced by breakpoints have been relocated to | https:/cls.orginedia/3466_ml00_archived_ecvs table pdt
the CLSI website.

Abbreviations: ECY, epidemiological cutoff value; QC, quality control.

inated from M100 since 2010 have been | hitps:/clsi org/iedia/2654/_m100_archived_drugs table 2019 pdt

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Testing Mission Statement

The Subcommittee on Antimicrobial Susceptibility Testing is composed of representatives from the professions, government, and industry,
including microbiology laboratories, government agencies, health care providers and educators, and pharmaceutical and diagnostic microbiology
industries. Using the CLSI voluntary consensus process, the subcommittee develops standards that promote accurate antimicrobial susceptibility
testing and appropriate reporting. The mission of the Subcommittee on Antimicrobial Susceptibility Testing is to

+ Develop standard reference methods for antimicrobial susceptibility tests

+ Provide quality control parameters for standard test methods.

+ Establish breakpoints and interpretive categories for the results of standard antimicrobial susceptibility tests and provide epidemiological
cutoff values when breakpoints are not available

+ Provide suggestions for testing and reporting strategies that are clinically relevant and cost-effective

+ Continually refine standards and optimize detection of emerging resistance mechanisms through development of new or revised methods,
breakpoints, and quality control parameters.

+ Educate users through multimedia communication of standards and guidelines.
+ Foster a dialogue with users of these methods and those who apply them.

‘The ultimate purpose of the subcommittee’s mission is to provide useful information to enable laboratories to assist the clinician in the selection of
appropriate antimicrobial therapy for patient care. The standards and guidelines are meant to be comprehensive and to include all antimicrobial
agents for which the data meet established CLSI guidelines. The values that guide this mission are quality, accuracy, faimess, timeliness,
teamwork, consensus, and trust.

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Instructions for Use of Tables

These instructions apply to:

+ Tables 1A and 1B: suggested groupings of antimicrobial agents that should be considered for testing and reporting by microbiology
laboratories, These guidelines are based on antimicrobial agents approved by the US Food and Drug Administration (FDA) for clinical use
in the United States. In other countries, placement of antimicrobial agents in Tables 1A and 1B should be based on available drugs
approved for clinical use by relevant regulatory organizations,

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‘+ Tables 2A through 21: tables for each organism group that contain:

— Recommended testing conditions

= Routine QC recommendations (also see Chapter 4 in M02! and M07°)

— General comments for testing the organism group and specific comments for testing particular agent/organism combinations

- Suggested agents that should be considered for routine testing and reporting by medical microbiology laboratories, as specified in
Tables 1A and IB (test/report groups A, B, C, U)

— Additional drugs that are appropriate for the respective organism group but would generally not warrant routine testing by a medical
microbiology laboratory in the United States (test/report group O for “other”; tesUreport group Inv. for “investigational” [not yet FDA
approved)

— Zone diameter and minimal inhibitory concentration (MIC) breakpoints

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+ Tables 1C and 23: tables containing specific recommendations for testing and reporting results on anaerobes and some of the information
listed in the bullets above

+ Tables 3A to 3J: tables describing tests to detect particular resistance types in specific organisms or organism groups

I. Selecting Antimicrobial Agents for Testing and Reporting
A. Selecting the most appropriate antimicrobial agents to test and report is a decision best made by each laboratory in consultation with the
infectious diseases and pharmacy practitioners, the pharmacy and therapeutics and infection prevention committees of the medical staff,

: and the antimicrobial stewardship team. The recommendations for each organism group include agents of proven efficacy that show

acceptable in vitro test performance. Considerations in the assignment of agents to specific test/report groups include clinical efficacy,
prevalence of resistance, minimizing emergence of resistance, cost, FDA clinical indications for use, and current consensus
recommendations for first-choice and alternative drugs. Tests on selected agents may be useful for infection prevention purposes.

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Drugs listed together in a single box are agents for which interpretive categories (susceptible, intermediate, or resistant) and clinical
efficacy are similar. Within each box, an “or” between agents indicates agents for which cross-resistance and cross-susceptibility are
neatly complete, Results from one agent connected by an “or” can be used to predict results for the other agent (le, equivalent agents).
For example, Enterobacterales susceptible to cefotaxime can be considered susceptible to ceftriaxone. The results obtained from testing
cefotaxime could be reported along with a comment that the isolate is also susceptible to ceftriaxone. For drugs connected with an “or,”
combined major and very major errors are fewer than 3%, and minor errors are fewer than 10%, based on a large population of bacteria
tested (see CLSI document M23° for description of error types). In addition, to qualify for an “or,” at least 100 strains with resistance to
the agents in question must be tested, and a result of “resistant” must be obtained with all agents for at least 95% of the strains. “Or” is
also used for comparable agents when tested against organisms for which “susceptible-only” breakpoints are provided (eg, cefotaxime or
ceftriaxone with H. influenzae). When no “or” connects agents within a box, testing of one agent cannot be used to predict results for
another, owing either to discrepancies or insufficient data

‘Test/Report Groups

Group A antimicrobial agents, as listed in Tables 1A, 1B, and 1C, are considered appropriate for inclusion in a routine, primary testing
panel, as well as for routine reporting of results for the specific organism groups.

Group B includes antimicrobial agents that may warrant primary testing, but they may be reported only selectively, such as when the
organism is resistant to agents of the same antimicrobial class, as in group A. Other indications for reporting the result might include a
selected specimen source (eg, a third-generation cephalosporin for enteric bacilli from cerebrospinal fluid (CSF) or trimethoprim-
sulfamethoxazole for urinary tract isolates); a polymicrobial infection: infections involving multiple sites; cases of patient allergy,
intolerance, or failure to respond to an antimicrobial agent in group A; or for infection prevention.

Group C includes altemative or supplemental antimicrobial agents that may necessitate testing in those institutions that harbor endemic or
epidemic strains resistant to several of the primary drugs (especially in the same class, eg, B-lactams); for treatment of patients allergic to
primary drugs; for treatment of unusual organisms (eg, chloramphenicol for extraintestinal isolates of Salmonella spp.); or for reporting to
infection prevention as an epidemiological aid,

Group U (“urine”) includes certain antimicrobial agents (eg, nitrofurantoin and certain quinolones) that are used only or primarily for
treating UTIs. These agents should not be routinely reported against pathogens recovered from other infection sites. An exception to this
rule is for Enterobacterales in Table 1A, in which cefazolin is listed as a surrogate agent for oral cephalosporins, Other antimicrobial
agents with broader indications may be included in group U for specific urinary pathogens (eg, Enterococcus and ciprofloxacin),

Group O (“other”) includes antimicrobial agents that have a clinical indication for the organism group but are generally not candidates
for routine testing and reporting in the United States,

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Group Inv. (“investigational”) includes antimicrobial agents that are investigational for the organism group and have not yet been
approved by the FDA foruse in the United States.

Selective Reporting.

Each laboratory should decide which agents in the tables to report routinely (group A) and which might be reported only selectively (from
group B), in consultation with the infectious diseases and pharmacy practitioners, the pharmacy and therapeutics and infection prevention
committees of the health care institution, and the antimicrobial stewardship team. Selective reporting should improve the clinical relevance
of test reports and help minimize the selection of multiresistant, health care-associated strains by overusing broad-spectrum antimicrobial
agents. Results for group B antimicrobial agents tested, but not reported routinely, should be available on request, or they may be reported
for selected specimen types. Unexpected resistance, when confirmed, should be reported (eg, resistance to a secondary agent but
susceptibility to a primary agent, such as a P. aeruginosa isolate resistant to amikacin but susceptible to tobramycin; as such, both drugs
should be reported). In addition, each laboratory should develop a protocol to cover isolates that are confirmed as resistant to all agents on
its routine test panels. This protocol should include options for testing additional agents in-house or sending the isolate to a referral
laboratory.

Breakpoint and Interpretive Category Definitions

Breakpoint — minimal inhibitory concentration (MIC) or zone diameter value used to categorize an organism as susceptible, susceptible-
dose dependent, intermediate, resistant, or nonsusceptible; NOTE 1: MIC or zone diameter values generated by a susceptibility test can be
interpreted based on established breakpoints; NOTE 2: Because breakpoints are based on pharmacologically and clinically rich datasets
using in vitro and in vivo data, they are considered robust predictors of likely clinical outcome; NOTE 3: Also known as “clinical
breakpoint”; NOTE 4: See interpretive category.

Interpretive category — category derived from microbiological characteristics, pharmacokinetic-phamacodynamic parameters, and
clinical outcome data, when available, NOTE 1: MIC or zone diameter values generated by a susceptibility test can be interpreted based
‘on established breakpoints, NOTE 2: See breakpoint.

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EXAMPLE:
| interpretive Break:points‘

Category MIC, pg/mL | Zone Diameter, mm
Susceptible <4 220
Susceptible-dose 8-16 15-19
dependent

| Intermediate 3-16 15-19
Resistant 232 14
[Nonsusceptible >1 <ı7

MIC or zone diameter value breakpoints and interpretive categories are established per CLSI document M23° for categories of susceptible,
intermediate, and resistant (and susceptible-dose dependent and nonsusceptible, when appropriate).

+ susceptible (S) - a category defined by a breakpoint that implies that isolates with an MIC at or below or a zone diameter at or above
the susceptible breakpoint are inhibited by the usually achievable concentrations of antimicrobial agent when the dosage
recommended to treat the site of infection is used, resulting in likely clinical efficacy.

+ susceptible-dose dependent (SDD) — a category defined by a breakpoint that implies that susceptibility of an isolate depends on the
dosage regimen that is used in the patient. To achieve levels that are likely to be clinically effective against isolates for which the
susceptibility testing results (either MICs or zone diameters) are in the SDD category, it is necessary to use a dosage regimen
(ie, higher doses, more frequent doses, or both) that results in higher drug exposure than that achieved with the dose that was used to
establish the susceptible breakpoint. Consideration should be given to the maximum, literature-supported dosage regimen, because
higher exposure gives the highest probability of adequate coverage of an SDD isolate. Appendix E lists the doses used when
establishing SDD categories. The drug label should be consulted for recommended doses and adjustment for organ function;
NOTE: The SDD category may be assigned when doses well above those used to calculate the susceptible breakpoint are supported
by the literature, widely used clinically, and/or approved and for which sufficient data to justify the designation exist and have been
reviewed. This category also includes a buffer zone for inherent variability in test methods, which should prevent small,
uncontrolled, technical factors from causing major discrepancies in interpretations, especially for drugs with narrow
pharmacotoxicity margins. See Appendix F for additional information,

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+ intermediate () - a category defined by a breakpoint that includes isolates with MICs or zone diameters within the intermediate
range that approach usually attainable blood and tissue levels and/or for which response rates may be lower than for susceptible
isolates; NOTE: The intermediate category implies clinical efficacy in anatomical sites where the drugs are physiologically
concentrated. An I with a “*” in Tables 2 indicates agents that have the potential to concentrate at an anatomical site. The I
category also includes a buffer zone for inherent variability in test methods, which should prevent small, uncontrolled, technical
factors from causing major discrepancies in interpretations, especially for drugs with narrow pharmacotoxicity margins.

+ resistant (R) — a category defined by a breakpoint that implies that isolates with an MIC at or above or a zone diameter at or below
the resistant breakpoint are not inhibited by the usually achievable concentrations of the agent with normal dosage schedules and/or
that demonstrate MICs or zone diameters that fall in the range in which specific microbial resistance mechanisms are likely, and
clinical efficacy of the agent against the isolate has not been reliably shown in treatment studies.

+ nonsusceptible (NS) — a category used for isolates for which only a susceptible breakpoint is designated because of the absence or
rare occurrence of resistant strains. Isolates for which the antimicrobial agent MICs are above or the zone diameters are below the
value indicated for the susceptible breakpoint should be reported as nonsusceptible; NOTE 1: An isolate that is interpreted as
nonsusceptible does not necessarily mean that the isolate has a resistance mechanism. It is possible that isolates with MICs above the
susceptible breakpoint that lack resistance mechanisms may be encountered within the wild-type distribution after the time the
susceptible-only breakpoint was set; NOTE 2: The term “nonsusceptible” should not be used when the text is describing an
organism/drug category with intermediate and resistant interpretive categories. Isolates that are in the categories of “intermediate” or
“resistant” could be called “not susceptible” rather than “nonsusceptible.”

Example of Breakpoints and Interpretive Categories as Used in Table 2

Interpretive

Categories and Zone | Interpretive Categories

Diameter Breakpoints, | and MIC Breakpoints,

Antimicrobial Disk nearest whole mm ng/mL,

Agent Content Ss im RS r R

x 308 >20 | 15-19 | <14 | <a | 8-16 | 232
Y - = = | = | «a 2 24
z 10 ng >16 | - | - | st - -

“Or SDD, if appropriate
Abbreviations 1, intermediate; R, resistant; S, susceptible; SDD, suscepible-dose dependent

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For antimicrobial agent X with breakpoints in the table above, the susceptible breakpoint is <4 g/ml or >20 mm and the resistant
breakpoint is > 32 g/mL. or < 14 mm. For some antimicrobial agents (eg, antimicrobial agent Y), only MIC breakpoints may be available.
For these agents, the disk diffusion zone diameters do not correlate with MIC values or data have not been evaluated as described in
CLSI document M23.* Technical issues may also preclude the use of the disk diffusion method for some agents. For some antimicrobial
agents (eg, antimicrobial agent Z) only a “susceptible” category exists, For these agents, the absence or rare occurrence of resistant strains
precludes defining any results categories other than “susceptible.” For strains yielding results suggestive of a “nonsusceptible” category,
organism identification and antimicrobial susceptibility test results should be confirmed (see Appendix A). In examples Y and Z, a dash
mark (-) indicates a disk is not available or that breakpoints are not applicable

Reporting Results
Organisms Included in Table 2

‘The MIC values determined as described in MO7° may be reported directly to clinicians for patient care purposes. However, it is essential
that an interpretive category result (S, SDD, I, R, or NS) also be provided routinely to facilitate understanding of the MIC report by
clinicians, Zone diameter measurements without an interpretive category should not be reported, Recommended interpretive categories for
various MIC and zone diameter values are included in tables for each organism group and are based on the evaluation of data as described
in CLSI document M23.°

Laboratories should only report results for agents listed in Table 2 specific to the organism being tested. It is not appropriate to apply disk
diffusion or MIC breakpoints borrowed from a table in which the organism is not listed. There may be rare cases for which an agent may
be appropriate for an isolate but for which there are no CLSI breakpoints (eg, tigecycline). In these cases, the FDA prescribing information
document for the agent should be consulted

For more information on reporting epidemiological cutoff values in the medical laboratory, see Appendix G.
Organisms Excluded From Table 2

For some organism groups excluded from Tables 2A through 21, CLSI document M4S° provides suggestions for standardized methods for
AST, including information about drug selection, interpretation, and QC. The organism groups covered in that guideline are Abiotrophia
and Granulicatella spp. (formerly known as nutritionally deficient or nutritionally variant streptococci), Aerococcus spp; Aeromonas Spp.;
Bacillus spp. (not Bacillus anthracis), Campylobacter jejuni/coli; Corynebacterium spp. (including Corynebacterium diphtheriae),
Erysipelothrix rhusiopathiae; Gemella spp: the HACEK group: Aggregatibacter spp. (formerly Haemophilus aphrophilus, Haemophilus
paraphrophilus, Haemophilus segnis, and Actinobacillus actinomycetemcomitans), Cardiobacterium spp., Eikenella corrodens, and
Kingella spp: Helicobacter pylori; Lactobacillus spp: Lactococcus spp: Leuconostoc spp; Listeria monocytogenes; Micrococcus Sp
Moraxella catarrhalis; Pasteurella spp, Pediococcus spp. Rothia mucilaginosa; potential agents of bioterrorism; and Vibrio spp.,
including Vibrio cholerae.

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For organisms other than those in the groups mentioned above, studies are not yet adequate to develop reproducible, definitive standards
to interpret results, These organisms may need different media or different incubation atmospheres, or they may show marked strain-to-
strain variation in growth rate. For these microorganisms, consultation with an infectious diseases specialist is recommended for guidance
in determining the need for susceptibility testing and in results interpretation. Published reports in the medical literature and current
consensus recommendations for therapy of uncommon microorganisms may preclude the need for testing. If necessary, a dilution method
usually is the most appropriate testing method, and this may necessitate submitting the organism to a referral laboratory. Physicians should
be informed of the limitations of results and advised to interpret results with caution.

Cumulative Antibiograms
Policies regarding the generation of cumulative antibiograms should be developed together with the infectious diseases service, infection
prevention personnel, the pharmacy and therapeutics committee, and the antimicrobial stewardship team. See CLSI document M397 for
detailed instructions on generating cumulative antibiograms,

MIC Reporting Concentrations

‘When serial twofold dilution MICs are being prepared and tested, the actual dilution scheme is, eg

16, 8,4, 2, 1, 0.5, 0.25, 0.125, 0.0625, 0.03125 pg/mL, ete. (see Table 7 for additional dilutions).

For convenience only, not because these are the actual concentrations tested, it was decided to use the following values in Tables 7, 8A,
and $B: 16, 8, 4, 2, 1, 0.5, 0.25, 0.12, 0.06, 0.03 ng/mL, etc

‘The values that appear in the tables are equivalent to the actual values tested, eg, 0.12 g/mL. =
report an MIC of <0.125 ug/mL as <0.12 pg/mL.

125 jig/mL., and laboratories should

Therapy-Related Comments

Some comments in the tables relate to therapy concerns. These are denoted with an Rx symbol. It may be appropriate to include some of
these comments (or modifications thereof) on the patient report. An example would be inclusion of a comment when rifampin is being
reported stating that “Rifampin should not be used alone for antimicrobial therapy.” Antimicrobial dosage regimens often vary widely
among practitioners and institutions. In some cases, the MIC breakpoints rely on pharmacokinetic-phannacodynamic (PK-PD) data, using.
specific human dosage regimens. In cases in which specific dosage regimens are important for properly applying breakpoints, the dosage
regimen is listed. These dosage regimen comments are not generally intended for use on individual patient reports

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Confirmation of Patient Results

Multiple test parameters are monitored by following the QC recommendations described in M100, However, acceptable results derived
from testing QC strains do not guarantee accurate results when testing patient isolates. It is important to review all the results obtained
from all drugs tested on a patient's isolate before reporting the results, This review should include but not be limited to ensuring that 1) the
AST results are consistent with the identification of the isolate; 2) the results from individual agents within a specific drug class follow the
established hierarchy of activity rules (eg, in general, third-generation cephems are more active than first- or second-generation cephems
against Enterobacterales), and 3) the isolate is susceptible to those agents for which resistance has not been documented (eg, vancomycin
and Streptococcus spp.) and for which only “susceptible” breakpoints exist in M100.

Unusual or inconsistent results should be confirmed by rechecking various testing parameters detailed in Appendix A. Each laboratory
must develop its own policies for confirming unusual or inconsistent antimicrobial susceptibility test results, The list provided in
Appendix A emphasizes results that are most likely to affect patient care.

Development of Resistance and Testing of Repeat Isolates

Isolates that are initially susceptible may become intermediate or resistant after therapy is initiated. Therefore, subsequent isolates of the
same species from a similar anatomical site should be tested to detect resistance that may have developed. Development of resistance can
occur within as little as three to four days and has been noted most frequently in Enterobacter (including Klebsiella [formerly
Enterobacter] aerogenes), Citrobacter, and Serratia spp. with third-generation cephalosporins, in P. aeruginosa with all antimicrobial
agents, and in staphylococci with fluoroquinolones. For $. aureus, vancomycin-susceptible isolates may become vancomycin intermediate
during the course of prolonged therapy.

In certain circumstances, the decision to perform susceptibility tests on subsequent isolates necessitates knowledge of the specific situation
and the severity of the patient's condition (eg, an isolate of E. cloacae from a blood culture on a premature infant or methicillin
(oxacillin)-tesistant 5. aureus [MRSA] from a patient with prolonged bacteremia), Laboratory guidelines on when to perform
susceptibility testing on repeat isolates should be determined after consultation with the medical staff

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Warning

Some of the comments in the tables relate to dangerously misleading results that can occur when certain antimicrobial agents are tested
and reported as susceptible against specific organisms. These are denoted with the word “Warning.”

Location Organism Antimicrobial Agents
“Warning”: The following antimicrobial agent/organism combinations may appear active in vitro but are not effective clinically and
must not be reported as susceptible.
Table 2A ‘Salmonella spp. Shigella spp. Tst- and 2nd-generation cephalosporins, cephamyeins, and aminoglycosides

Table 2D Enterococcus spp, ‘Aminoglycosides (except for high-level resistance testing), cephalosporins,
clindamycin, and trimethoprim-sulfamethoxazole

“Warning”: The following antimicrobial agents that are included in this document should not be routinely reported for
bacteria isolated from CSF. These antimicrobial agents are not the drugs of choice and may not be effective for treating CSF
infections caused by these organisms (ie, the bacteria included in Tables 2A through 2):

Tables 2A Bacteria isolated from CSF ‘Agents administered by oral route only, 1st- and 2nd-generation

through 27 cephalosporins and cephamycins, clindamycin, macrolides, tetracyclines,
and fluoroquinolones

Abri

CSF, cerebrospinal Mud

Routine, Supplemental, Screening, Surrogate Agent, and Equivalent Agent Testing to Determine Susceptibility and Resistance to
Antimicrobial Agents

‘The testing categories are defined as follows
+ Routine test: disk diffusion or broth or agar dilution MIC tests for routine clinical testing
‘+ Supplemental (not routine) test: test that detects susceptibility or resistance to a drug or drug class by method other than routine disk
diffusion or broth or agar dilution MIC and does not need additional tests to confirm susceptibility or resistance
— Some supplemental tests identify a specific resistance mechanism and may be required or optional for reporting specific clinical

results

+ Screening test: test that provides presumptive results; additional testing typically only needed for a specific result (eg, only if screen
is positive)

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+ Surrogate agent test: test performed with an agent that replaces a test performed with the antimicrobial agent of interest and is used
when the agent of interest cannot be tested due to availability or performance issues (eg, surrogate agent performs better than the agent
of interest)

‘+ Equivalent agent test: test performed with an agent that predicts results of closely related agents of the same class and increases
efficiency by limiting testing of multiple closely related agents. Equivalent agents are identified by:
= Listing equivalent agents with an “or” in Tables 1 and 2. “Or” indicates cross-susceptibility and cross-resistance is nearly
complete (very major error +major error < 3%; minor error < 10%) and only one agent needs to be tested.

= Listing agents that are equivalent and results that can be deduced by testing the equivalent agent in a comment (see Tables 1 and
2.
The following tables include tests that fall into the supplemental, screening, sumogate agent, and equivalent agent test categories. The
tables for supplemental, screening, and surrogate agent tests are comprehensive. The table for equivalent agent tests includes several
examples, and many other equivalent agent tests are described throughout Tables 1 and 2.

‘Supplemental Tests (Required)

Table
Supplemental Test Organisms Test Description Required for: Location
Tnducible + Staphylococcus spp. | Broth microdilution or disk | Isolates that test erythromycin resistant 3H
ndamy cin + $ pneumoniae difusion with clindamycin | and clindamyein susceptible or
resistance + Streptococcus spp and erythromycin tested ntermediate before reporting the isolate
B-hemolytic group together as clindamycin susceptible

Placiamase Staphylococcus spp. | Chromogenic cephalosporin | Isolates that test penicilin susceptible sE
(al staphylococci), before reporting the isolate as penicillin
penicillin disk diffusion zene- | susceptible
edge test (S aureus only)

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: ‘Supplemental Tests (Optional) El
5 Table El
: Supplemental Test Organisms ‘Test Description Optional for: Location E
: ESBL + Ecol Broth microdilution or disk | Tsofates demonstrating reduced 3A 2
À + K pretmonice difusion clavulanate susceptibility to cephalosporins Fi
4 + Klebsiella oxytoca inhibition test for ESBLS I
+ Proteus mirabilis Results hat indicate presence or absence E
of ESBLS E
A Cabanp + Enterobacterales Colorimeiie assay for Tsolates demonstrating reduced 38,351 $
E + P.ceruginosa detecting carbapenem susceptibility to carbapenems
E hydrolysis
: Results that indicate presence or absence
of certain carbapenemases
: TCIM with or + mi only Disk diffusion for detecting — | Isolates demonstrating reduced 30
: without eCIM Enterobacterales and — | carbapenem hydrolysis susceptibility to cabapenems
: P aeruginosa inactivation)
+ mCIM with eCIM ae Remis hat date presence orense
eCIM add
À Enterobacterales only | o. | certain carbapenemases
À B-lctamases from serine
À carbapenemases in
Enterobacteralesisolates that
: are positive for CIM
: Colistin agar test | + Enterobacterales Modified agar dilution Determining the colistin MIC D
7 + P. aeruginosa
5 Colistin broth disk | « Enterobacterales Tube dilution using colisún | Determining the colistin MIC D
elution © Po aeruginosa disks as antimicrobial agent
Oxacilin saltagar [+ S aureus ‘Agar dilution, MINA with 46 | Detecting MRSA, see cefoxitin surogate ES
NaCl and 6 yl oxacillin _| agent tests, which are preferred
Altraiañons eCIN, EDTAsmodified carbapenen inadivation method, ESBL, extendedspecinan f+laciamase; mCIM, modified carbapenem inacvation method,
MHA, Mueller-Hinton azar, MIC, minimal inhibitory concentration; MRSA, mehiilin (oxadlin)-reiant Staphylococcus avt
E
B |S
: E

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When to Perform
Screening Test Organisms Test Description | Confirmatory Test | Confirmatory Test | Table Location
Vancomycin agar | + S. aureus ‘Agar dilution; BHI with | Ifsereen positive | Vancomycin MIC 36
screen + Enterococcus | 6 jig/ml vancomycin
spp.
HLAR by disk © Enterococcus ‘Disk diffusion with If screen Broth microdilution, agar 3
diffusion sp. gentamicin and inconclusive dilution MIC
streptomycin.
Abbreviations BHT, brain heat nfision; HEAR, hial-level minos cod reses; MIC, minimal ny concentran.
‘Surrogate Agent Tests
Surrogate Table
Agent Organisms. Test Description Results Location
Cefxzolin + Ecol Broth microdilution or disk | When used for therapy of uncomplicated UTIs, TA ZA
+ Klebsiella diffusion predicts results for the following oral antimicrobial
pneumoniae agents: cefacior, cefdinir, cefpodoxime, cefprozil,
+ P. mirabilis ‘cefuroxime, cephalexin, and loracarbef
Cefazolin as a surrogate may overcall resistance to
cefdinir, cefpodoxime, and cefuroxime. If cefazolin
tests resistant, test these drugs individually if needed
for therap
Cefoxitin + S aureus Broth microdihtion: Predicts result For mecc-mediated methiciin TA, 20, 3F
+ S lugaunensis S aueus (oxacillin) resistance,
+ S epidermicis S lugdimensis
+ Other
Stæplwococeus spp. | Disk diffusion:
(excluding S. S aureus
pseudimermedias — | S luedunensis
‘and schleifri) | Other Staphylococeus spp.,
excluding S
seudintermedius and
schlejfert
Osacilin = S pneumoniae Disk diffusion Predicts penieilin susceptiiliy iF oxacllin zone à 15,26
220 mun. If oxacillin zone is <19 mm, penicillin MIC
rust be done.
Pefloxacin |e Salmonella spp. | Disk diffusion Predicts reduced aiscepibility lo ciprofloxacin E73

Abbreviations NIE, mi

a i

bitory concentration; PBP2a, penicl

inding protein 2x, UTA, urinary tract infection.

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to predict the activity of amoxicill

Agents ‘Organisms Identified by Table Location
Cefotaxime or Enterobacterales “Or TA and 24
ceftriaxone
Colistin or Enterobacterales, “Or” 2A, 2B-1, and 282
polymyxin B Pseudomonas aeruginosa,
Acinetobacter baumannii
complex
‘Azithromycin or ‘Staphylococcus spp. “OF TA md2¢
clarithromycin or
erythromycin
Penicillin-susceptible staphylococci are susceptible to other | Staphylococens spp. Note listed TA and2C
B-lactam agents with established clinical eff
staphylococcal infections (including both pen
and penicillinase-stable agents; see Glossary 1), Penicillin-
resistant staphylococci are resistant to penicillinase-Iabile
penicill
‘The results of ampicillin susceptibility tests should be used | Haemophilus spp. Note listed TB and2E
to predict the activity of amoxicill
‘The results of ampicillin susceptibility tests should be used | Anacrobes Note listed a

Quality Control and Verification

Recommendations for QC are included in various tables and appendixes. Acceptable ranges for QC strains are provided in Tables 44-1
through 4B for disk diffusion and Tables SA-1 through SE for MIC testing. Guidance for QC frequency and modifications of AST systems
is found in Table 4C for disk diffusion and Table SF for MIC testing, Guidance for troubleshooting out-of-range results is included in
Table 4D for disk diffusion and Table SG for MIC testing. Additional information is available in Appendix C (eg, QC organism

characteristics, QC testing recommendations),

Implementing any new diagnostic test requires verification Each laboratory that introduces a new AST system or adds a new
antimicrobial agent to an existing AST system must verify or establish that, before reporting patient test results, the system meets
performance specifications for that system. Verification generally involves testing patient isolates with the new AST system and
comparing results to those obtained with an established reference method or a system that has been previously verified. Testing patient
isolates may be done concurrently with the two systems. Altematively, organisms with known MICs or zone sizes may be used for the
verification. Guidance on verification studies is not included in this document. Other publications describe AST system verification

(eg, CLSI document M52? and Patel J, et al)

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: X. Abbreviations and Acronyms E
: AST antimicrobial susceptibility testing, 2
: aTcc® American Type Culture Collection E
: BHI Drain heart infusion 2
A BLNAR P-lactamase negative, ampicillin-resistant
a BMHA blood Mueller-Hinton agar
a BSC biological safety cabinet
BSL-2 biosafety level 2
BSL-3 biosafety level 3
q CAMHB cation-adjusted Mueller-Hinton broth
: CAT colistin agar test
À CBDE colistin broth disk elution
: CFU colony-forming unit(s)
: CMRNG chromosomally mediated penicillin-resistant Neisseria gonorrhoeae
: CSF cerebrospinal fluid
À DMSO dimethyl sulfoxide
A ECV epidemiological cutoff value
: ecIM EDTA-modified carbapenem inactivation method
EDTA ethylenediaminetetraacetic acid
ESBL extended-spectrum f-lactamase
FDA US Food and Drug Administration
HLAR high-level aminoglycoside resistance
: HTM Haemophilus test medium
: 1 intermediate
À ICR inducible clindamycin resistance
IM intramuscular
D identification
LHB lysed horse blood
mCIM modified carbapenem inactivation method El
MHA ‘Mueller-Hinton agar El
MH-F agar Mueller-Hinton fastidious agar bl
E
* ATCC® is a registered trademark ofthe American Type Culture Collection. S
E
El

El
E
3
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5
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MHB
MIC
MRS
MRSA
NAD
NCTC
NPBP
NS
NWT
PBP2a
PCR
PK-PD
pH

Qc

SDD
TSA
TSB
UTI
WT

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‘Mueller-Hinton broth
minimal inhibitory concentration

‘methicillin (oxacillin)-resistant staphylococci
‘methicillin (oxacillin)-resistant Staphylococcus aureus
B-nicotinamide adenine dinucleotide

‘National Collection of Type Cultures

no previous breakpoint existed

nonsusceptible

non-wild-type

penicillin-binding protein 2a

polymerase chain reaction
pharmacokinetic-pharmacodynamic

negative logarithm of hydrogen ion concentration
quality control

resistant

susceptible

susceptible-dose dependent

tryptic soy agar

trypticase soy broth

‘urinary tract infection

wild-type

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References

References

Y CLSL Performance Sandarde for Areatcrobtal Disk Susceptilty Test. 13th ed. CLSI standard MO), Wayne, PA: Clinical and Laboratory Standard Insitute; 2018.

2 CLSL Methode for Dilution Antamtcrobiel Susceptibility Teste for Bacteria That Grow Aerobically. Mh ed. CLSI standard MO7. Wayne, PA: Clinical and Laboratory Standards
Institute; 2018.

2 CASI Methods for antimicrobial Susceptibility Term of Anzerobie Bacteria, 9h ed CLS standard ML. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

* Adeolu M, Alnajar $, Naushad S, Gupta RS. Genome-based phylogeny and taxonomy of the Enterobacteiles: proposal for Enterobacteraes ord, nav. vided into the families
Buerobactenacese, Ensimcceas fam. nov. Pectobacteracece fam. nov, Yersimzcece fam nov, Hafniacece fam. nov., Morganellacece fam. nov, and Budviciecese fam. nov.
Int J Spat Eva Microbiol. 2016:66(12)5575-5599.

5 CLSL Development ofa Vito Suceptbly Teig Chr and Quai Control Porometers Sth ed. CLSI guideline MBS. Wayne, PA: Clinical and Laboratory Standards Instat;
zu.

© CLSL Methode for Antmierobil Dion and Dick Suscepnibliy Testing of Ifrequently Ioleted or Fastdious Bactera. rd ed. CLST guideline MAS, Wayne, PA: Clinical and
Laboratory Standards Institute; 2016.

7 CASE Analysis and Presentation of Goma Antimicrobial Susceptibility Test Data; Approved Guideline—Fourh Edition. CLST document M39-A4. Wayne, PA: Clinical and
Laboratory Standards Institute; 2014.

* Centers for Medicare & Medicaid Services, US Department of Health and Human Services. Pore 493 Laboratory Reguiroments; Standard: Extablishment and verification of
performance specifications (Codified at 42 CER §493.1253). Office of the Federal Register, published anally

% CLSL Fenficaion of Commercial Microbial Idenicaton and Antimtrobiel Siscopräility Teetng Systems. 1 ed CLSI guideline MS2, Wayne, PA: Clinical and Laboratory
Standard Institute; 2015.

12 Patel J Sharp S, Novak-Weebley S. Verification of antimicrobial susceptibility testing methods: a practical approach. Cin Microbiol Newslet, 2013:35(13)103-109.

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For Use With MO2 and MO7

M100, 36th ed.

This page is intentionally left blank.

Clinical and Laboratory Standards Institute. All rights reserved.

17

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Table 1A

Suggested Nonfastidious Groupings
= ‘M02 and MO7 .

Table 1A. Suggested Groupings of Antimicrobial Agents Approved by the US Food and Drug Administration for Clinical Use That
‘Should Be Considered for Testing and Reporting on Nonfastidious Organisms by Microbiology Laboratories in the United States

results forthe specific organism group.

‘Group A: Includes antimicrobial agents considered appropriate for inclusion in a routine, primary testing panel, as well as for routine reporting of

‘Trimethoprim sulfamethoxazole

Enterobacterales. Pseudomonas aeruginosa Jlococcus spp. Enterococcus spp.“
Ampicilin® Ceftazidime ‘Azithromycin’ or “Ampicilin®
Cefazolin® Gentamicin clarithromycin’ or Penicilin?
Tobramycin erythromycin’
‘Gentamicin? Piperacilin-tazobactam Gindamycin®
Tobramycin" Oxacili
Cefoxtin)t
(Surrogate test for oxacilin)
enicilin’

‘Group B: Includes antimicrobial agents that may warrant primary testing but may be reported only selectively, su
to agents of the same antimicrobial class in Group A.°

ich as when the organism Is resistant

Ertapenem
Imipenem

Meropenem
Trimethoprim-sulfamethorazole"

Amikacin® ‘Amikacin Cefardline" Daptomycin"
‘Amoxicilin-clavulanate Aztreonam Daptomyain Linezolid
‘Ampicilin-sulbactam Tedizolid?
‘Ceftazidime avibactam Cefepime Unezoid ‘Vancomycin
‘Ceftolozane-tazobactam Ceftazidme avibaciam Tedizolid
‘Meropenem-vaborbactam CeRolozane tazobactam
Piperacilin-tazobactam
Cefuroxime Ciproffoxacin Doxyeycine
Levofloxacin yl
pme Doripenem Tetracyeline®
Cefotetan Imipenem ‘Vancomycin
Cefoxitin Meropenem
Rifampia”

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PRA O A A aan ae |
Table AA. (Continued) El
(Group C: Includes alternative or supplemental antimicrobial agents that may require testing in institutions that harbor endemic or epidemic strains pl
resistant to several of the primary drugs, for treatment of patients allergic to primary drugs, for treatment of unusual organisms, or for reporting to €
infection prevention as an epidemiological aid. El
Enterobacterales Pseudomonas aeruginosa ‘Staphylococcus spp. Enterococcus spp." El
Adraonam ChloramphenicaF Gentamicin higrlevel 3
Cetazidme resistance testing ony) 5
Giproforacin or Streptemyein (high-level E
levofloxacin resistance testing only) E
TS Moxifoxacin
Dalbavandn'”
Geniamicn” Oritavancin""
Dalbavancin'" Telavancin""
Oritavancin”
Telavancin
‘Group U: Includes antimicrobial agents that are used only or primarily for treating UTIs.
Cefazolin Nirofurantoin Ciprofloxacin
(Gurrogate test for uncomplicated UT) Levofloxacin
Fosfomycin" Sulfsoxazole
Nitofuranten “Trimethoprim Fostomyent
Sulfisoxazole Nitofurantin
“Trimethoprim Tetracycline?
“Group A: Includes antimicrobial agents considered appropriate for inclusion in a routine, primary testing panel, as well as for routine reporting Of
results forthe specific organism
‘Acinetobacter spp. Burkhoïderia cepacia complex maltophila | Other Non-Enterobacterales™
“Arpiclin-subactam Levofloxacin” Levofloxacin Ceftazidime
Ceftazidime Meropenem Minocycline Gentami
Giprofoxacin Trimethoprim-sulfameihoxazale thoprim sulfamethoxazole | Tobramyein
Levofloxacin
Doripenem
Imipenem
Meropenem
Gentamicin
Tobramycin
ES
=

Table 10

Suggested Nonfastdious Groupings
Si MO2 and MO7 .

"pasas SUBI [IV PAS PUIS LLOWUOGDT PAO PAUDS

Table 1A

Suggested Nonfastidious Groupings
= ‘M02 and MO7 .

Table 1A. (Continued)

‘Group B: Includes antimicrobial agents that may warrant primary testing but may be reported only selectively, such as when the organism is resistant
to agents of the same antimicrobial class in Group A.*

Cefazicime Cofaziime” ‘Amikacin
Minoeycline Aztreonam
Cefepime
Cefotaxime Ciprofioxacin
Levofloxacin
Doxycycline Imipenem
Minocyctine Meropenem
Trimethoprim-sulfamethoxazole Piperacilin-tazobactam

Trimeth oprim-sulfamethoxazole

‘Group C: includes alternative or supplemental antimicrobial agents that may require testing in institutions that harbor endemic or epidemic strains
resistant to several of the primary drugs, for treatment of patients allergic to primary drugs, for treatment of unusual organisms, or for reporting to
infection prevention as an epidemiological aid.

‘ChloramphenicoF ‘Chloramphenicol Cefotaxime
Cefriaxone
‘ChloramphenicoP
(Group U: Includes antimicrobial agents that are used only or primarily for treating UTIs.
Tetracycline” Sulfsoxazole
Tetracyeline®

‘Aboreviatons: MIC, minimal inhibitory concentration; UTI, urinary va infection
* MIC tasting only; dk difusion test is unreliable

1 See oxacılin and cefoxitin comments in Table 2C for using cefoxitin as a surrogate for oxacilin.

+ See cefazolin comments in Table 2A for using cefazalin as a surrogate for oral cephalosporins and for reporting cefazolin when used for therapy in uncomplicated
ur.

For S. aureus, S. lugdunensis, and other Staphylococcus spp. (excluding S. epidermidis, S. pseudintermedius, and S. schleifer), only MC testing, not
disk diffusion testing, is acceptable; see exceptions in Table 2C.

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al Table 1A. (Continued) El
E: El
E: “Warning”: The following antimicrobial agents that are included in this document should not be routinely reported for bacteria ë
ee isolated from CSF. These antimicrobial agents are not the drugs of choice and may not be effective for treating CSF infections caused E
E by these organisms (ie, the bacteria included in Tables 2A through 24): E
E ‘© Agents administered by oral route only El
A + 1st- and 2nd-generation cephalosporins and cephamycins E
a: + Clindamycin 4
2: |. mecroïdes
8: + Tetracyctines
q: + Fluoroquinolones
E General
È a. Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline and minocycline. However, some organisms that
= are intermediate or resistant to tetracycline may be susceptible to doxycycline, minocycline, or both.
Él >. Natroulinely reported on organisms isolated frm Ihe urinary tract
A
Section |, C.2. in the Instructions for Use of Tables lists additional examples of when a Group B agent might be reported.
Enterobacterales
d. WARNING: For Salmonella spp. and Shigella spp., aminoglycosides, first- and second-generation cephalosporins, and cephamycins may
appear active in vitro, but are not effective clinically and should not be reported as susceptible.
Routine susceptibility testing is not indicated for nontyphoidal Salmonella spp. isolated from intestinal sources. In contrast, susceptibility
testing is indicated for all Shigella isolates.
When fecal isolates of Salmonella and Shigella spp. are tested, only ampicilin, a fluoroquinolone, and trimethoprim-Sulfamethoxazale should
be reported routinely. In addition, for extraintestinal isolates of Salmonella spp., a third-generation cephalosporin should be tested and
reported, and if requested, chloramphenicol may be tested and reported. Susceptibility testing is indicated for typhoidal Salmonella
(S. enterica ser. Typhi and Salmonella enterica ser. Paratyphi A-C) isolated from extraintestinal and intestinal sources. z
© e, Cefotaxime or ceftriaxone should be tested and reported on isolates from CSF in place of cefazolin, Ed
£ 2
ss . For testing and reporting of E. col urinary tract isolates only. E

Table 10

Suggested Nonfastdious Groupings
Si MO2 and MO7 .

"pasas SUBI [IV PAS PUIS LLOWUOGDT PAO PAUDS

Table 1A

Suggested Nonfastidious Groupings
= ‘M02 and MO7 .

Table 1A. (Continued)

Other Non-Enterobacı

9. Other non-Enterobacterales include Pseudomonas spp. and other nonfastidious, glucose-nonfermenting, gram-negative bacili but exclude
P. aeruginosa, Acinetobacter spp., B. cepacia complex, and S. maltophilia. Refer to each respective organism column for suggested
antimicrobial agents to test and report.

Recommendations for testing and reporting of Aeromonas hydrophila complex, Burkholderia mallei, Burkholderia pseudomallei, and Vibrio
spp. (including V. cholerae) are found in CLSI document M45."

‘Staphylococcus spp.
h. R

ifampin should not be used alone for antimicrobial therapy.
i. For S. aureus only, including methicilin (oxacillin)-resistant S. aureus (MRSA).

j. Penicilin-susceptible staphylococci are also susceptible to other f-lactam agents with established clinical efficacy for staphylococcal
infections. Penicilin-resistant staphylococci are resistant to penicilinase-labile penicillins. Methicillin (oxacilin)-resistant staphylococci are
resistant to all currently available f-lactam antimicrobial agents, with the exception of ceftaroline. Thus, susceptibility or resistance to a wide
array of B-lactam antimicrobial agents may be deduced from testing only penicillin and either cefoxitin or oxacilin. Routine testing of other P-
lactam agents, except ceftaroline, is not advised.

k. Daptomycin should not be reported for isolates from the respiratory tract,

1. Ifa penicilinase-stable penicillin is tested, oxacillin is the preferred agent, and results can be applied to the other penicilinase-stable
penicilins (refer to Glossary 1). Detection of methicillin (oxacilin) resistance in staphylococci is achieved by using specific methods as
described in Tables 20 and 3F.

m. For staphylococci that test susceptible, gentamicin is used only in combination with other active agents that test susceptible.

Enterococcus spp.

n. Warning: For Enterococcus spp., cephalosporins, aminoglycosides (except for high-level resistance testing), clindamycin, and trimethoprim-
sulfamethoxazole may appear active in vitro, but are not effective clinically and should not be reported as susceptible.

o. The results of ampicillin susceptibility tests should be used to predict the activity of amoxicillin. Ampicilin results may be used to predict
susceptibility to amoxicillin-clavulanate, ampicilin-sulbactam, and piperacillin-tazobactam among non-f-lactamase-producing enterococci.
Ampicilin susceptibility can be used to predict imipenem susceptibility, providing the species is confirmed to be Enterococcus faecalis.

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Fi Table 1A. (Continued) El
E 5
E p. Enterococci susceptible to penicilin are predictably susceptible to ampicilin, amoxicilin, ampicilin-sulbactam, amoxicilin-clavulanate, and a
8: Piperacli-tazobactam for non-f-lactamase-producing enterococei However, enterococd! susceptible to ampiclin carnat be assumed tobe |S
a susceptible to penicilin. if penicilin results are needed, testing of penicilin is required. Rx: Combination therapy with ampicilin, penicilin, or E
À vancomycin (for susceptible strains) plus an aminoglycoside is usually indicated for serious enterococcal infections, such as endocarditis, 8
unless high-level resistance to both gentamicin and streptomycin is documented; such combinations are predicted to result in synergistic Fi
8: Killing of the Enterococcus. For strains with low-level penicillin or ampicillin resistance when combination therapy with a B-lactam is being 2
at considered, see additional testing and reporting information in Table 34.2 8
2:
3] q. Fortesting and reporting of E. faecalis ony.
5 $. Fortesting and reporting of vancomycin-susceptible E. faecalls only.
& References for Table 1A
$: Y GLSI. Methods for Antimicrobial Dilution and Disk Susceptibilty Testing of Infrequentiy Isolated or Fastidious Bacteria. 3rd ed. CLSI guideline
E M45, Wayne, PA: Clinical and Laboratory Standards Institute; 2016.
2: ? Murray BE, Arias CA, Nannini EC. Glycopeptides (vancomycin and teicoplanin), streptogramins (quinupristin-dalfopristin), lipopeptides
Ä (daptomycin), and lipoglycopeptides (tetavancin). In: Bennett JE, Dolin R, Blaser MJ. Mardell, Douglas, and Bennett's Principles and Practice
of Infectious Diseases. 8th ed. Philadelphia, PA: Elsevier Saunders; 2015:377-400.
E
: E

Table 10

Suggested Nonfastdious Groupings
Si MO2 and MO7 .

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Table 18

Suggested Fastidious Groupings
ne ‘M02 and MO7 ®

Table 1B. Suggested Groupings of Antimicrobial Agents Approved by the US Food and Drug Administration for Clinical Use That
Should Be Considered for Testing and Reporting on Fastidious Organisms by Microbiology Laboratories in the United States

results for the specific organism group.

‘Group A: Includes antimicrobial agents considered appropriate for inclusion in a routine, primary testing panel, as well as for routine reporting of

rn
ee ED Fe == ee
pneumoniae B-Hemolytic Group? Viridans Group’
Ampicilin*3 Azithromycin + Erythromycin** Clndamyein“® “Ampieiiin™
Cefiximet
Ciprofloxacin’ Penicillin” Erythromycin? =?
Tetracycline" {oxacillin disk) Penicillin®*t or
ce pt
includes antimicı ‘agents that may warrant primary testing but may be reported only selectively, such as the organism is resistant
N
mine Ge mr GES
Cabo GF Cefotaxime!” ‘cefotaxime or Cefotaxime
A ne m Sem
er ee nn
ee
Levofloxacin’
moxifloxacin Moxifloxacin'
es Nr

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8 Table 18. (Continued) El
g “Group C; Includes alternative or supplemental antimicrobial agents that may require testing in institutions that harbor endemic or epidemic strains El
E resistant to several of the primary drugs, for treatment of patients allergic to primary drugs, for treatment of unusual organisms, or for reporting to E
E infection prevention as an epidemiological ald. E
E Haemophilus influenzae? and ‘Neisseria ‘Streptococcus ‘Streptococcus spp. ‘Streptococcus spp. E
Haemophilus paralnfluenzae. gonormoeae ‘pneumoniae B-Hemolytic Group Viridans Group“ E
‘Aaithromycin’ Amor Cetaraline Ceclozane-tazobactam 5
E Clarithromycin ‘Amoxicilin-lavulanate™ E
Gi teers Coloma” ETT omnes” E
2: Amoxiilin-cvulanate” Coaroine Daplomycin" Ciindamycin=
gi Cefacior Chloramphenicol Levofoxacin Enythromycin==
Fl Cefproil
z Cel’ or Erapanam Thess
ES cofxime or imipenem Tedizoid:
3 cofpodoxime! Dalbavancin®™ 4
E Oritavancin Oritavancin"
id ae Telavancin Telavancin®
5 Cefuroxime!
E: ‘GhloramphenicoF
Si [en
3: Rifampin’
ES Tetracycline?
“Trimethoprim-slfamethoxazole
‘Abbreviations: CSF, cerebrospinal Ad, MIC, minimal ihibtery concentration
“NIC testing only: sk difusion test is unreliable
+ Routine testing fs not necessary (see foctntes ando)
5
: Ea

Table 18

Suggested Fastiious Groupings
se MO2 and MO7 .

"pasas SUBI [IV PAS PUIS LLOWUOGDT PAO PAUDS

Table 18

Suggested Fastidious Groupings
ne ‘M02 and MO7 ®

Table 1B. (Continued)
“Warning”: The following antimicrobial agents that are included in this document should not be routinely reported for bacteria
isolated from CSF. These antimicrobial agents are not the drugs of choice and may not be effective for treating CSF infections caused
by these organisms (ie, the bacteria included in Tables 2A through 2J):

Agents administered by oral route only

1st- and 2nd-generation cephalosporins and cephamycins
Clindamyein

Macrolides

Tetracyclines

Fluoroquinolones

a. Susceptibiity and resistance to azithromycin, larthromycin, and dirthromycin can be predicted by testing erythromycin

b. Organisms that are susceptible to tetracycline are also considered susceptible to doxyeycline and minocycline

e. Not routinely reported for organisms isolated from the urinary tract

d._ Section I, C.2. in the Instructions for Use of Tables lists additional examples of when a Group B agent might be reported.
Haemophilus spp.

e. For isolates of H. influenzae from CSF, only results of testing with ampicillin, any of the third-generation cephalosporins listed, and
meropenem are appropriate to report

{. Amoxicillin-ctavulanate, azithromycin, cefaclor, cefdinir, cefixime, cefpodoxime, cefprozil, cefuroxime, and clarithromycin are used as empiric,
therapy for respiratory tract infections due to Haemophilus spp. The results of susceptibility tests with these antimicrobial agents are often not
necessary for managing individual patients.

9. The results of ampicilin susceptibility tests should be used to predict the activity of amoxicillin. The majority of H. influenzae isolates that are
resistant to ampicilin and amoxicilin produce a TEM-type f-lactamase. In most cases, a direct f-lactamase test can provide a rapid means of
detecting ampicillin and amoxicilin resistance,

h. For H. influenzae only.

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al Table 18. (Continued) El
g: El
E: i. Maybe appropriate only for prophylaxis of case contacts. Refer to Table 2E.
: El
8 E
E Neisseria gonorrhoeae E
À? cute and cuscetity esting o gonorhnge sould be canina in caos reine alu Arico agent recommended tor |g
E testing include, at a minimum, the agents Isted in group A. The most current guidelines for treatment and testing are avaiable from the |5
5: Centers for Disease Control and Prevention at https:/Awww.ode.govIstd/gonorrhealstdfact-gonorrhea.htm. 8
2:
©] Streptococcus pneumoniae
sau in io nin sy ww ani i i pc
È susceptible to gemifloxacin or moxifloxacin cannot be assumed to be susceptible to levofloxacin.
5 |. Penicilin and cefotaxime, ceftriaxone, or meropenem should be tested by a reliable MIC method (such as that described in MO7!) and
= reported routinely with CSF isolates of S. pneumoniae. Such isolates can also be tested against vancomycin using the MIC or disk diffusion
= method. With isolates from other sites, the oxacilin disk test may be used. If the oxacilin zone size is < 19 mm, penicilin, cefotaxime,
= ceftriaxone, or meropenem MICs should be determined.
3 m. Rx: Rifampin should not be used alone for antimicrobial therapy.
El
ES ‘Streptococcus spp.
n. Rx: Penicilin- or ampieilin-intermediate isolates may necessitate combined therapy with an aminoglycoside for bactericidal action.
: ©. Penicilin and ampicilin are drugs of choice for treating B-hemolytic streptococcal infections. Susceptibility testing of penicillins and other p-
: lactams approved by the US Food and Drug Administration for treating B-hemolytic streptococcal infections does not need to be performed
: routinely, because nonsusceptible isolates (ie, penicilin MICs > 0.12 and ampicilin MICs > 0.25 ygimL) are extremely rare in any B-hemolytic
: streptococci and have not been reported for Streptococcus pyogenes. I testing is performed, any B-hemolytic streptococcal isolate found to be
: nonsusceptible should be re-identified, retested, and, if confirmed, submitted to a public health laboratory (see Appendix A for additional
instructions)
À E
: E

Table 18

Suggested Fastiious Groupings
se MO2 and MO7 .

"pasas SUBI [IV PAS PUIS LLOWUOGDT PAO PAUDS

Table 18

Suggested Fastidious Groupings
ne ‘M02 and MO7 ®

Table 1B. (Continued)

p. Rx: Recommendations for intrapartum prophylaxis for group B streptococci are penicillin or ampicilin. Although cefazolin is recommended for
penicilin-allergic women at low risk for anaphylaxis, those at high risk for anaphylaxis may receive clindamycin. Group B streptococci are
susceptible to ampicillin, penicillin, and cefazolin, but may be resistant to erythromycin and clindamycin. When group B Streptococcus is
isolated from a pregnant woman with severe penicilin allergy (high risk for anaphylaxis), erythromycin and clindamycin (including inducible
clindamycin resistance [ICR]) should be tested, and only clindamycin should be reported. Erythromycin, even when tested for
determination of ICR, should not be reported. See Table 3H.

4. For this table, the B-hemolytic group includes the large colony-forming pyogenic strains of streptococci with group A (S. pyogenes), C, or G
antigens and strains with group B (S. agalactiae) antigen. Small colony-forming B-hemolytic strains with group A, C, F, or G antigens
(Streptococcus anginosus group, previously termed “Streptococcus miller’) are considered part of the viridans group, and breakpoints for the
viridans group should be used

r.. Daptomycin should not be reported for isolates from the respiratory tract,

s. For reporting against S. pyogenes and Streptococcus agalactiae only

t. For reporting against S. anginosus group (includes S. anginosus, Streptococcus intermedius, and Streptococcus constellatus) only.

u. For reporting against S. pyogenes, S. agalactiae, Streptococcus dysgalactiae, and S. anginosus group

NOTE 1: For information about the selection of appropriate antimicrobial agents; explanation of testreport groups A, B, ©, and U; and explanation

of the listing of agents within boxes, including the meaning of “or” between agents, refer to the Instructions for Use of Tables that precede Table

1A

NOTE 2: Information in boldface type is new or modified since the previous edition

Reference for Table 1B

1 CLSI. Methods for Dilution Antimicrobial Susceptibilty Tests for Bacteria That Grow Aerobically. 11th ed. CLSI standard M07. Wayne, PA:
Clinical and Laboratory Standards Institute; 2018.

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For Use With MO2 and MO7

‘M100, 30th ed

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Clinical and Laboratory Standards Institute. All rights reserved.

Table 10
Suggested Anaerobe Groupings
[3 macro E

g Table 1C. Suggested Groupings of Antimicrobial Agents Approved by the US Food and Drug Administration for Clinical Use That E
Should Be Considered for Testing and Reporting on Anaerobic Organisms by Microbiology Laboratories in the United States E
‘Group A: Includes antimicrobial agents considered to be appropriate for inclusion in a routine, primary testing panel, as well as for routine reporting] E
of results forthe specific organism group. 2
Gram-Negative Anaerobes Gram-Positive Anaerobes® y
‘Amoxicillin-clavulanate Ampicillin” La
Ampicillin-sulbactam Penicillin?
Piperacli-tazobactam Amosiclin-elavulanate
Ampicillin-sulbactam
Piperacilin-tazobactam
Cindamyein Cindamyein
Doripenem Deripenem
Entapenem Eitapenem
imipenem imipenem
Meropenem Meropenem
Metronidazole Metronidazole
“Group €: includes alternative or supplemental antimicrobial agents that may require testing in institutions that harbor endemic or epidemic strains
resistant to several of the primary drugs, for treatment of patients allergic to primary drugs, for treatment of unusual organisms, or for reporting to
8 infection prevention as an epidemiological aid.
Peniciin®
E Anielin®
E Cefotetan Cefotetan
a: Cefoxitin Cefoxitn
2: ‘Ceftizoxime Ceftizoxime
Ceftriaxone Cefriaxone
a: Moxifloxacin
8: Tetracycline
2:
£
à Footnotes
x HB a. Many non-spore-forming, gram-positive anaerobic rods are resistant to metronidazole (see Appendix D).
EJE
3 b. If f-lactamase positive, report as resistant to penicillin and ampicillin. Be aware that f-lactamase-negative isolates may be resistant to
8: penicilin and ampicilin by other mechanisms.
a
E: <
5: E
ay El
a El
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8: Table 1C. (Continued) El
Ss El
E NOTE 4: For information about the selection of appropriate antimicrobial agents; explanation of test/report groups A and C; and explanation of the a
Si listing of agents within boxes, refer to the Instructions for Use of Tables that precede Table 1A. E
3 El
NOTE 2: Most anaerobic infections are polymicrobial, including both B-lactamase-positive and B-lactamase-negative strains. Testing may not be E
necessary for isolates associated with polymicrobial anaerobic infections. However, if susceptibility testing is requested, only the organism most
N likely to be resistant (eg, Bacteroides spp. and Parabacteroides spp.) should be tested and results reported (see Appendix D),
a:
gl NOTE 3: Specific Clostridium spp. (eg, Clostridium septicum, Clostridium sordelli) may be the singular cause of infection and are typically
3 ! susceptibleto penlllin and ampiciln. Penicilin and cindamycin resistance have been reported in Clostridium perfringens. Agents in group A of
2 : Table 1C should be tested and reported for Clostridium spp.
E NOTE 4: Information in boldface type is new or modified since the previous edition.
E
È
5
El
El
A
À E
: E

Table 1C

Suggested Anaerobe Groupings
[3 nero E

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Table 28
Enterobacterales

‘Mo2 and MO7

Table 2A. Zone Diameter and MIC Breakpoints for Enterobacterales

Testing Conditions Routine QC Recommendations (see Tables 4A-1 and 5A-1 for acceptable
OC ranges)
Medium: Disk diffusion: MHA
Broth dilution: CAMHB; irondepleted CANHB for | | Escherichia coli ATCC® 25922

cefiderocol (see Appendix}! Pseudomonas aeruginosa ATCO®27853 (for carbapenems)
‘Agar dition: MHA Staphylococcus aureus ATCC? 25923 (for Salmonella enterica ser.
Inoculum: Broth culture method or colony suspension, equivalent to a | | Typhi azithromycin disk diffusion testing only; see Table 44-1)
05 McFarland standard
Incubation: 35°C::2°C; ambient air Refer to Tables 44-2 and SA-2 to select strains for routine QC of lactam
Disk difusion: 16-18 hours combination agents.

Dilution methods: 16-20 hours
When a commercial test system is used for susceptiilty testing, refer to the
‘manufacturer’ instructions for QC test recommendations and QC ranges.

Refer to Tables 3A, 38, and 3C for additional testing, reporting, and QC for Enterobacterales.
General Comments

(1) For disk diffusion, test a maximum of 12 disks on a 150-mm plate and no more than 6 disks on a 100-mm plate; disks should be placed no less than 24 mm
apart, center to center (see M02.’ Subchapter 3.6). Each zone diameter should be clearly measurable; overlapping zones prevent accurate measurement.
Measure the diameter of the zones of complete inibiion (as judged by the unaided eye), including the diameter of the disk (see the M02 Disk Difusion
Reading Guide). Hold the Pet plate a few inches above a black background iluminated with reflected light. The zone margin should be considered the area
showing no obvious, visible growth that can be detected withthe unaided eye. Ignore faint growth oftiny colonies that can be detected only with a magnifying
lens at the edge ofthe zone of inhibited growth. Strains of Proteus spp. may swarm into areas of inhibited growth around certain antimicrobial agents. With
Proteus spp. ignore the thin vell of swarming growth in an otherwise obvious zone of growth inhibition. With trimethoprim and the sulfonamides, antagonists in
{ho medium may allow some sight growth; therefore, dsregard sight growth (20% or less of the lawn of growth) and measure Ihe more obvious margin to
determine the zone diameter.

(2) When fecal isolates of Salmonella and Shigella spp. are tested, only ampiellin, a fuoroquinolone, and timethopri sulfamethoxazole should be reported
routinely. In action, for extraintestinal isolates of Saimonella spp.. a 3rá generation cephalosporin should be tested and reported, and chloramphenicol may
be tested and reported if requested, Susceptbilty testing is indicated for typhoidal Salmonella (S. enterica ser. Typhi and S. enterica ser. Paratyphi A-C)
isolated from extraintestinal and intestinal sources. Routine susceptbity testing is not indicated for nontyphoidal Salmonella spp. isolated ftom intestinal
sources. I contra, susceptibility tesing is indicated for all Shigella isolates.

(3) The dosage regimens shown in the comments column below are those needed to achieve plasma drug exposures (in adults with normal renal and hepatic
functions) on which breakpoints were based. When implementing new breakpoints, itis strongly recommended that laboratories share this information with
infectious diseases practitioners, pharmacists, pharmacy and therapeutics committees, infection prevention committees, and the antimicrobial stewardship
team,

(4) Intermediate ranges denoted with a **” for the applicable antimicrobial agents in the drug groups in Tables 2 are based on the known ability of
these agents to concentrate in the urine; some agents may also have the potential to concentrate at other anatomical sites (eg, epithelial lining).

NOTE: Information in boldface type is new or modified since the previous edition.

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ae Table 2A. Enterobacterales (Continued) 3
8: Tatarprative Categories and Tnterprative Categories and El
5 Zone Diameter Breakpoints, Mic Breakpoints, 5
a TestRepor | Antimicrobial Disk nearest whole mm vom. 2
8: Group Agent content | 5} 00; ı TRIOS jr 1 z Comments E
Ls PENICILONS Fi
2 A | Amialin Tug Je: - ii Bi FF 332 | @) Resuts of ampictn testing con be 5
io Used 1 pret results fr amaxtcin, Fi
á ii ¿ See general comment (2) E
E CN ETT on ap AA sm El
> 0 | Meca Mo [et = Tatar <i TT 232 | 6) Fortesing andreporing OTE cot
8: E i unary trac soles ony
à FLRCTANCOMEIRATION AGENTS,
: | Amowolinciavienate | 201099 | S181 = + Zea) 1 PI
5 © [Ampelinsubodem | 1009 [>15 5 = + EEE PT
È BT Cotolozano- ES SD = ana; 20m | (ER are based on a dosage
8: tazobactam i i : regimen of 15 g admnstered every 8h
8: B | Cotaıdmeanbacem | 302099 | 821: = Ta = 2154 | €) Brearpaies are based on a dosage
$ regmen of 25 9 (29 cetazidme+05 9
E ‘anbactam) every 3h administered over
E oh
5 (9) Confiematory MIC testing ls
El indicated for iolates with zones of
E 20-22 mm to avoid reporting false
2 E susceptible orfal
ES E Weropenem- Does | E18: = ATA ee sun: = E 31618 | (10) Breakpoints are based on a dosage
: veborbectam regimen of (2 9 meropenem + 29
a vaborbactam) every h eóminstered
: Er
EE EP EE A STR
6] NN 75710ug EN EE 1
E
: |8
: E

Table 2A

Enterobacterales
‘02 and MO7

ve

“PAS SHBU IF “IIS SPIDPUDIS CLORIOGPT PLO [PMID

Table 2A
Enterobacterales

‘Mo2 and MO7

Table 2A. Enterobacterales (Continued)

Interpretive Categories and Interpreive Categories and
Zone Diameter Breakpoints, ‘MIC Breakpoints,
TesuReport | Antimicrobial Disk nearest whole mm ‘git
Group. Agent Content | 5 | sop; 1 IR] Ss [soi 71 E Comments

CEPHEMS (PARENTERAL) (Including cephalosporins |i I and IV Please refer to Glossary)

(11) WARNING: For Salmonela spp. and Shigella spp, 1st- and 2nd-generation cephalosporins and cephamycins may appear active vito but are nat effective clinical and
‘should not be reported as susceptible,

(12) Foloning evaluation of PK-PD properts, limted cinical data, and MIC dstibutions, revised breakpoints for cephalosparns (cefazolin, cafotaximo, ceftazidme, cefizoxime,
‘and cofriaxone) and aztreonam were frst published in January 2010 (100-520) and are listed in his table, Cefuroxime (parenteral) was also evaluated; however, no change in
breakpoints was necessary for the dosage indicated belon When using the current breakpoints, routine ESBL testing is no longer necessary before reporting resus (i, is no
longer necessary to edit rasuts for cephalosporins, aztreonam, or penclins from susceptbe o resistant). However, ESEL testing may sul be usaul for epidemiological orinfecton
prevention purposes. For laboratories that have not mplemerted the curent breakporris, ESEL testing shouldbe performed as described in Table 3A

[Breakpoints for drugs with imted avalebiit in many countries (eg, moxalactam, cefonicid, cefamandole, and cefoperazone) were not evaluated. If considering use ofthese drugs
fer E col, Klebsiella spp, or Proteus spp , ESEL testing should be performed (see Table 34) If isolates test ESBL postive the results for moxalactam, cefonid, cefamandole, and
(Cefoperazone should be reported as resistant

(13) Enterobacter, Klebsiella (fomery Enterobacter aerogenes, Citobacter, and Serrat may develop resistance during prolonged therapy wih 3rd-generation cephalosporins as
2 result of derepression of AmpC lactamase. Therefore, isolates that are int susceptible may become resistant wihin 3 to 4 days after intation of therapy. Testing repeat
isolates may be warranted

À [Caron Wu Jen: - E 2 ı - 3 38 | (14) Breskporrts when cofacoln is used

fortnerapy of infections other than
Uncomplicated UTIs due to E col,
pneumoniae, and P. mrabite
Ereakpaits are based on a dosage
regimen of 2g administered every 8h
See comment (12)

ET Bo Es am; = = 232 | (18) Brearports when cofazain s used
À E tortnerapy of uncomplicated UTIs due to
E col, K pneumoniae, and P. mati
Erealpoint are based on a dosage
regimen of 1g administered every 12h

‘See ational information in CEPHEMS
(ORAL)

WIR TSI | 205 7 FT | (16) Breskparis are based on a dosage

regmen of 800 mg administored every
2h

O ET]

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g Table 2A. Enterobacterales (Continued) El
E Interpreliv Categories and inirpreive Categories and El
E Zone Diameter Sreakpoint, MIC Breakpoint a
& Testmeport | Antimierobil Disk nearest whole mim mnie El
8 ‘Group ‘Agent content | 8 800 RTS sop ı z Comments E
E GEPHENS RER (ana aptos and N. Fine rieteClosan [Sonora] E
Cefepime Son zer) 48] 121 [WM Thebreaipont for suscephbie 8
Based on a dosage rogmen 0f 1 9 Fi
acministered every 12 . The breakpoint E
: for SDD 1 based on dosage regimens 3
3 {nat resu in ngner cotepme exposure, $
e: exer igh doses ar more fequert
: doses or both up to approved maximum
: dosage ragmens. See Append E for
à more informaton about resipoints and
E dosage ragmens Also ses te detntion
È of SDD inte isiuctons for Use of
E Tables section
5 E | Cations or Wis [38 IATA IT =; 3%: 21 | MM reakpoins are based ono dosage
= 5 catraxone soup | 228 donee sia] sı >: 24 | regimen of g aamnstrad evry 25m
5 torcotnacono a1 asma
à every for coloma,
È See Comment 2)
E mm TT EE ES EN EE
2 TIO ET] pa] RE aereas a based on a dosage
E H regimen ofat est 8g per day (03,29
2 i aaministered every en)
TO em 38} = FR | 530 | BOlBreahponts ar based on a dosage
regimen 011.59 admnsterad ever 8
See comment (121
© came ET] TE SRH = DORT EIS | Gi Breokponis ar based on a dosage
poi i i ragimen 011 9 admnstored every En
¡E ! | Seo comment (12)
CN OS Bon E E See comment (12)
NEO ig ES ES E E TEE nat
ii i | feevauatebreaigonts iso ner.
o SE ET] | 301133] Soo comment (12)
: D ceteperarone Ty 0000318373017 See comment
À O ET] — am] Si} [2] 24 | a) Breakpows ae based ona desago
: i i i fegmon 011 g administered every 12%
E See comment (12)
KO IS EMI =e eee SF 5] See comment (121 a
B IE
: E

Table 2A

Enterobacterales
‘02 and MO7

Table 2A
Enterobacterales

‘Mo2 and MO7

Table 2A. Enterobacterales (Continued) =
aaa lagoon and EE Categories and E
Zone Diameter Breakpoints MIC Breakpoints, |=
TestReport | Antimicrobial | Disk nearest whole mm rte pS
A Group, Agent content | 8 7 SD: 1 TR Som. I ER Comments E
3 (CEPHEMS (PARENTERAL) (ncluding cephalosporins, Il, and IV. Please refer to Glossary 1) (Continue ES
B im | Cader Sug | Be = BHA m | et OR STB) RE
regimen of? 9 every Sh administró
perl
CERN OR
© Comm Sug EE ee | a) a
0 | coton E EE ELU
(surrogate test for Used asa surrogate testo predct
Sra espnaispoms rests or e oa agar nor
Sra ineomplcaes Celoni cofpodoum cf
oti) traine cepneloin, ad loracarbot
iran used fr theapy of uncomplested
Us due to cal À preuronas and
P minis
À Cefacoin s a sumogat may overcal
ai resistance to cal cobpodocme, and
g: Sehrosme 1 nfaoin est restart
=: festivo uns navy need or
Ê: ir
5 7 [ia | AAA TA | asen Dos Provence
N E E 104 Se Enerobaterspp win cairn or
: lobe by disk sin because flse-
: : Since ess have boon reported
= | En,
a o Tefador 30 ug E TARTA sa ; — | 16% 7 232 | See comment (25).
§ ‘oT etn Sa EE [et ata Top comments a
0 Terme Sn sie 1 Sp meet gen | en tt 2e 24 | BMD Movorai sp mn
8 io i BO es te eee
i i dskattison
E To 9 aces TS comments TE
E M
id El
E
5 i
€ E
i E
a: E
A E

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ae Table 2A. Enterobacterales (Continued) 3
8: Interpretive Categories and interpretive Categories and El
E Zone Diameter Breakpoints, MIC Breakpeints, 5
a TestReport | Antimierobial | Disk nearest whole mm gt. 2
8: Group Agent content [575001 1 TRI] S 750 1 TOR Comments E
2: CEPHENS ORAL) (Continued) Fi
È a ° Cefprozil Sn | 218 ı = : WA: st4] <8: - : 18% ] 232 | @B)Donottest Provdencia spp. win I
Getrozi by disk difusion because flse- 2
‘Susceptible resus have been reported E
5 See comment (25) 3
3 Im. Cofetamet 1069 | 218 1 = EMI] a ]- TO { 316 | See comment (27) =
e: inv] ceden Bug | emi mamis] ss = 16 232 | ator testing ond raponng furry
: H i i i act isolates ony
: MONOBACTANS
! © | Adivonam wus] E Pam] <4 { = [8 [ 216 | (@0}Breshpomis re based on a dosage
ES regimen of 1 g adminsterad every 6
E: i i i ‘Seo comment (121
Si ‘CARBAPENENS
Le (81) Following evaluation of PD properties, ited clinical data, and MIC distribution that indude recent described carbapanemase-producng stains, sed breakpais for
S Cardepenems were fst published in June 2010 (M100-520-U) and ar Isied below. Because of ited treatment options fr infections caused by organisms with caıbapenem
E ICS orzone diameters n the intermediate range, ciniiens may wish o design cafbapenem dosage regimens that use maximum recommended doses and possibly prolonged
= intravenous intsion regimens, as has been reported inthe ratura 7 Consultant an ifechous dscases pracitoner recommend fr Isolates for which the cabapenem
S MICs or zone diameter resuks from disk difusion teng are in the intermediate or resistant ranges
a: Laboratones using Enterobsetersls MIC traipoins fr crbapanams described in M100-520 (January 2010) shoud perom tha CarbaNP tos, mCIM, 8CM, andor a
E molecular assay refer to Tables 38 and 3C for methods) when isolates of Enterobacterales are suspicious for carbapenamase production based on imipenem or meropenem
Mics 2-4 igor erapenem MIC 2 ugimL (rearto Tables 3E-1 and 3C-1 for guidance on reportng) Ater mplementng he current breakpoints, tse addon tests may not
A need to be periomed other than for epidemiological or infection prevention purposes (i, t is no longer necessary to edit resus forthe carbapenems to resistant if à
À catbapenamase producers detected) See Appendix H, Tab H3 regarding suggestions for reporting when molecular and phenotypie methods are discordant
‘Te folowing information is provided as background on carbapenemases in Enterabacterale that are largely responsible for MICs and zone diamatrsin th intermediate and
resistant ranges, and tus the rationale fr seting revised carbapenem breakpoints
À + The nica tfectvaness of carbapenem treatment of infections produced by soltes for which the carbapenem MIC or sk fusion test resus ae wahin the ntemedtate
E range is uncertain due to lack of controled cinical studies
“+ imipenem MIOS for Proteus spp. Povilencia spp , and Morganelia morgani tend to be higher (eg, MICS in the intermediate or resistant range) than meropenem or
À derperem MICS Tres les mayhaveslevaed mpenem MiGs bymechansms der than producien olcaepenemases
a © | Donpanem Tong | 223: - | 20-2 1 <19 2) {24 | (62]Eroalgaris ar based ona dosage
: i ¿ Î regimen of 500 mg administered every
4 H sn
: © Tenapanam Tim RE teten TT 37 | 3) Broatparis ae based ono dosage
: H regimen 011 9 administered every 287 he
=P imipenem Tous [ent E ES TT ET aay Brooks ore based ona dosage E
i E regimen of 500 mg adminstered every E
e i H shor igevey/ oh IS
: E

Table 2A

Enterobacterales
‘02 and MO7

Table 28

Enterobacterales
‘Mo2 and MO7

8: Table 2A. Enterobacterales (Continued) =
: Trterprative Categories and Tr Categories and 3
: Zone Diameter Breakpeints, "WIC Breakpoits, El
TestRepor | Antimierobiat | Disk ‘nearest whole mm ui pS
Group. Agent Content [ST SoD | 1 Rs I 00 i e Comments E
‘GARBAPENEWS (Continued) £
© | Meropanam "m [en - [mmlenfet- 7 =i] 68) Eruaipon's aro basedona
dosage regimen oft 9 admisiered
cuen an
UPOPEPTID
(25) WARNING: Clinical and PK-PD data demonstrate colistin and polymyxin 8 have limited clinical afcacy, even I an intermediate results obtained, Altemative
{gents ae strongly prefered. Colin and polymyxin B should be used In combination with one or more active antimicrobial agents. Consultation with an infectious
es specialists recommended.
(21) Several species are Inrinsicaly resistant t th Ipopeptide (colstin and polymyxinB)-Referto Appendi B.
© | Colstmer en ee = 182% | 24 | Colistin(mathanesuifonate)
polymyain 8 LE) 2/2) sie) =» 24 | shouldbe given wi a loading dose
and maximum renal adjusted
doses (ee International Consensus
Guidelines",
A | | | (99) Polymyxin 8 should be given
8: | | th à loading dose and maximum
$: recommended doses [a
8: International Consensus
A Suldelines‘)
Su (40) When colistin or polymyxin Bis
È : given systemically, neither s tkely
i br effective for pneumonia
3 (41) For colisti, broth mierodiution,
CBDE, and CAT MIC methode are
E acceptable. For polymyxin B, broth
8: inierdilition the only approved
method. Disk difusion and gradient
ag \ performed (see Table 30).
È ANNOSLYEOSIDES 7
Bi (42) WARNING: For Salmonall spp. and Shoals spp. aminoglycosides may appear active in ito but ae not effchva cnica and should nat be reported a suscapttle <
as À | Sentamion ee en to 216 E
8: À | Tooramyen ou [is | = sun sn| fs | = | 0 BH 3
E E Amikacın Song par ps jos pp EJ E
8: ‘OT rename Sug Pete | = siesta | ete | = SL 1 A
oe © | Wetman EE ES LU ETC | ge ET LE ER ©
2: ©} Sinstanyen tug Test = peep ete =p = = 2
- : Z
A E

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oc Table 2A. Enterobacterales (Continued) El
8: interpretive Categories and interativo Categories and a
E Zone Diameter Breakpoints, MIC Breakpoints, E
ES Test Report | Antimicrobial | Disk nearest whole mm gm 2
a: Group Agent content LS So DR et R Comments E
a: MACROLIDE E
i inv aroma ej 213 | = = © [6 = | = | 232 | (3) enterleaser. Typhi only 8
Sreakpants aro based antic E
einbubon data and med cinc data E
5 Far $ founenand S some, ses E
q Appendix G, Table G1 Ss
8: TETRACYCUNES
4 (44) Organisms that are susceptible to tetracycline are also considered susceptible to doxycycline and minocycine. However, some organisms that are intermediate or resistant to
4 Hoi may be sucepiblet doneysine,mnaryine arta
ha ‘© | retrcyane Ma [2% a] 5 Le
È © TDoyeydne at = CE MTS
8: © | inseyeine 304g 1 216 is Ei CI ESO
8 ‘QUINOLONES AND FLUOROGUNOLONES for Enterebacieral (Pease ters lea)
8: © | Cprotoxeem Su | 22 =; 05%. 21 | 6jEreekporis br oprofoxaamare
5 8 | Covororacn sw | 221 ai 2 EM | besedona csege epmenat
E B 400 mg IV or 500 mg orally administered
= 05 every 12m.
3 (s)2eators brio an
3: ; Based ona dosage regimen of
2 i TED mg someras avery 4 n
: Tama mo EE o] comment 2).
: OT IET Too [Se | = mat em pe poes Sev comment 5)
A D [omiosen Sug [se] = piste fee ter) = ej.
: D | Gemitoresn Sug [2m | = mem |<] | 08 | 21 | rN For esting and eparing of
ds X oneumen on
À CO ET EE er ae E 38
B Oo Tremetorasn oa [en | = imma [ea = an ee
E A CET EE pia isa [ej — = IES EE
À | Nerfoxacin Mona | em te frame fen sa] = Fa | 210 | See comment 29)
oO frotorsen ES EE ES EE CI EE
à I TE Su Tv Djs] ej
: ‘QUINOLONES AND F LUOROGUNOLONES tor Salmonella app. Pease refer to Glossary)
a (40) For tesing and rpoting of Salmonsll spp. (nung S emteica ser. Typh aná S entries se. Parayphi A-C) Routine suscaptbtiy testing 5 not nácate for
: ‘ortphoidl Samenela spp Road fom testinal sources
(49) The profes test for assessing fuorogunolone susceptbity or resistance in Salmonella spp. 5 a oprooxach MIC test A evofoxeon or ofoxacn MIC est can be ES
paromediaihar agent respectively ste tuoroqundore af choice ina spectoacy. 11a prox lvotoxaon or ofoxacin MIC or cprefoxacn disk asin tet cant E
À fe done, pafoxaen dax sion may o Used as suarogte tnt pret eprofocacinsuscobity =
8 (60) No silo test detects resistance ring rom al possible Rüomauindonereitenoe mecharisms that have been dertifed in Salmons po E

Table 2A

Enterobacterales
‘02 and MO7

Table 2A
Enterobacterales

‘Mo2 and MO7

Table 2A. Enterobacterales (Continued) =
Interpretive Categories and Trerprative Categories and E
Zone Diameter Breakpoints ic Breakpoints, IS
Tesumeport | antimierobiat | où earest whole mim usin 2
Group Agent Content | 8; son; 1 TRIOS SD 1 TOR comments E
GUINOLONES AND FLUOROQUINOLONES for Salmonella spp. (Pease refer o Glossary [Continues] pl
| Chtouen Sun Jet 0 0200 — Os 21 | ON slats of Samora mattest
5 | Covotoracn Be RE TEN aan 22 | fet sscapttie cproforacn
Involosaen, ohoxaen. or paflosace m
be associated win cna fare or ane/ec
response in turoqunoione-reated
alerts il salmoneloss
oa => ee
m | Patera m Tr = wpe =] a Report rts opto
(surogste test for : SStepobieceresstant beses on he
profes) Baloxocn estres Peforocn il rot
À Gstect resistance in Salone app. due to
: 200 lor Petocecn ast ae not
A alain me Unico States
: Seo comment (5)
FOLATE PATHWAY ANTAGONISTS
À ® | Tomathopem- 129 Tate } PAE Tew] em = 1-1 24776] See ganerl comment 2)
8! sultametnorazole | 2075 y9 H i
$: TS SE STE
$: Em H H | Sry ofthe carey avaiable sulfonamide
ES ii i i Breperatong
5 a ESTI ESC en CI CI
Î: Eros
E NN ET EEE ai 232 | ah hak rue reparer on als om
a i Fa omo
E FOSFONVENS
O | Foam Wore PERLE E EL
3 Sony onyto E col unary ras sales
E ana should not be extrapolated to other
Species of Enerobactraes
E (66) The 200-ug fosfomycin disk contains.
E So ugotguceseoonospnate
3
3 (67) The only approved MIC method for E
E (sing aga din using agar meda El
E Supplemerted win 25 por of lucoses- E
& phosphate Broth ión MIC Lesung 2
= Srouldnot be pertornes E
5 E
8: ES
5: E
A E

"POMOS 104 $1 DUBUS HOMIEU 40 VOpROHENP PEZHOWINEUN "0202/62/10 - OB - MEN PUBUEMEQ - 3SdITD® ISTO

Qi Table2A. Enterobacterales (Continued) _ _ u El
$: inierpreive Categories and a
si MIC Breakpaints, a
fee Testmeport | Antimicrobial | Disk mL.
2 Es gent | content ee Comments E
E TITROFURANS: E
U Trova [went gsi; eu] 7-7 os + em] 8
‘Abbreviations: ATCC®, American Type Culture Collection; CAMHE, cation-adusted Mueller-Hinton broth; CAT, colistin agar test; CBDE, colisin broth disk E
á elution; eCIM, EDTA-modifed carbapenem inacivation method; ESBL, extendedspectrum f-lactamase; |, intermediate; IV, intravenous; mCIM, modified E
5 © carbapenem inactivation method; MHA Mueller-Hinton agar; MIC, minimal inhibitory concentration; PK-PD, pharmacckinetic-pharmacodynamic; OC, quality El
2] cond R resistant; S, susceptible; SDD, susceptibe-dose dependent; UT, urinary tract infect
g:
$ y Footnote
ha a. ATOOPis a registered trademark ofthe American Type Culture Collection.
E: References for Table 2A
& Y Hackel MA, Tsuji M, Yamono Y, Echols R, Karlowsky JA, Sahm DF. Reproducibility of broth microdilution MCs for the novel siderophore
= cephalosporin, cefiderocol, determined using iron-depleted cation-adjusted Mueller-Hinton broth. Diagn Microbiol Infect Dis. 2019;94(4):321-325.
È
E 2 CLSI Performance Standards for Antimicrobial Disk Susceptbity Tests. 13th ed. CLSI standard MO2. Wayne, PA: Clinical and Laboratory Standards
2 Institute; 2018.
2 3 CLSI. M2 Disk Diffusion Reading Guide. 1st ed. CLSI quick guide MO2QG. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
* Perrott J, Mabasa VH, Ensom MH. Comparing outcomes of meropenem administration strategies based on pharmacokinetic and pharmacodynamic
principles: a qualtaive systematic review. Ann Pharmacother 2010:44(3) 557-564.
% Chill, Vaccaro N, Tumer K Solanki B, Natarajan J, Redman R. Pharmacokinetics, safety, and tolerability of deipenem after 0.5, 1-, and 4-hour infusions in
healthy volunteers. J Cin Pharmacol, 2009:49(7)798:806
© Sakka SG, Glauner AK, Bultta JB, et al. Population pharmacokinetics and pharmacodynamics of continuous versus short-term infusion ofimipenen-cilastatin
in crticaly ll patients in a randomized, controlled tal. Antimicrob Agents Chemother. 2007:51(9):3304-3310.
7 Peleg AY, Hooper DC. Hospitakacquired infections due to gram-negative bacteria. N Engl J Med. 2010;362(19):1804-1813.
* Tsuji BT, Pogue JM, Zavaxcki AP, et al. Intemational consensus guidelines for the optimal use of the polymyxins: endorsed by the American
: College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Infectious Diseases Society of
B ‘America (IDSA), Intemational Society for Antı-Infective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious
: Diseases Pharmacists (SIDP). Pharmacotherapy. 2019:39(1):10-39. ES
: =

Table 2A

Enterobacterales
‘02 and MO7

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Table 28-1
Pseudomonas aeruginosa

‘M02 and Mo?

Table 2B-1. Zone Diameter and MIC Breakpoints for Pseudomonas aeruginosa

Testing Conditions Routine QC Recommendations (see Tables 44-1 and SA-1 for acceptable
QC ranges)
Medium: Disk diffusion: MHA
Broth dilution: CAMHB; iron-depleted CAMHB for | | Pseudomonas aeruginosa ATCC® 27853
cefiderocol (see Appendix 1)!

‘Agar dilution: MHA Refer to Tables 442 and 5A-2 to select strains for routine QC of F-lactam
Inoculum: Broth culture method or colony suspension, equivalent to a | | combination agents.
05 McFarland standard
Incubation: 35°C 2°C; ambient air When a commercial test system is used for susceptibilty testing, refer to the
Disk diffusion: 16-18 hours ‘manufacturer’ instructions for QC test recommendations and QC ranges.

Dilution methods: 16-20 hours

General Comments

(1) For disk diffusion, test a maximum of 12 disks on a 150-mm plate and no more than 6 disks on a 100-mm plate; isks should be placed no less than 24 mm
apart, center to center (see MO2,? Subchapter 3.6). Each zone diameter should be clearly measurable; overlapping zones prevent accurate measurement,
Measure the diameter of the zones of complete inhibition (as judged by the unaided eye), including the dameter of the disk (see the M02 Disk Difusion
Reading Guide). Hold the Pet plate afew inches above a black background iluminated with refected light. The zone margin should be considered the area
showing no obvious, visible growth that can be detected withthe unaided eye. Ignore faint growth oftiny colonies that can be detected only with a magnifying
lens at the edge of the zone of inhibited growth

(2) The susceptiblity of P. aeruginosa isolated from patients with cystic fbrosis can be reliably determined by disk difusion or dilution methods but may need
extended incubation for up to 24 hours before reporting as susceptible.

(8) P. aeruginosa may develop resistance during prolonged therapy with all antimicrobial agents. Therefore, isolates that are initially susceptible may become
resistant within 3 to 4 days after initiation of therapy, Testing of repeat isolates may be warranted.

(4) The dosage regimens shown in the comments column below are those necessary to achieve plasma drug exposures (in adults with normal renal and hepatic
functions) on which breakpoints were derived. When implementing new breakpoints, it is strongly recommended that laboratories share this information with
infectious diseases practitioners, pharmacists, pharmacy and therapeutics committees, infection prevention committees, and the antimicrobial stewardship
team,

(5) Intermediate ranges denoted with a“*” for the applicable antimicrobial agents in the drug groups in Tables 2 are based on the known ability of
these agents to concentrate in the urine; some agents may also have the potential to concentrate at other anatomical sites (eg, epithelial lining).

NOTE: Information in boldface type is new or modified since the previous edition.

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8 Table 2B-1. Pseudomonas aeruginosa (Continued) _ El
E interpretive Categories and | —interprative Categories and El
E Zone Diameter Breakpoints, MIC Breakpoints, a
& arest whole mm uit 2
3 Testteport | Antimicrobial Disk : E
E ‘Group Agent comet | 8 1 alos 1 R Comments E
FENICILLRS, E
© [Premia Tape EE FAP} 2126 | (Ereskoonts or pperasin (alone or wih 5
E tszoboctom) are based ona pperadlin E
7 H dosage regimen af atlas 9 administered E
5 i i H gieryen 8
& FLACTAN COMBINATION AGENTS
8: A |Poeralimtazobactem | 1O0MOpg | 221 ; 16-208 ] Sta | 164 1 324-040 à 21284 | (M)Broaigarts for pperacll (alone orwin
y H H tazobactam) are based ona pperactin
E à E dosage regimen oft east 39 edmiistered
5 i H san
È 5 | cotarameamtadan | ns | SA} = Tem | =f FTP | ta Breaks oe based on a dusage
E i Fegmen 0125929 stazidme+ 05 9
= i subactam)sdmnisiored every § hover 2h
| Cotetecanetazobactan | soon | 20] IA] | sea; GAN | 2104 | (G)Ereoponts om based on a dosage
& H H H Maman ott sg administered every on
= 5 TTeamimaandanate | Ou | EN] 18%] 5% | 2107 + STEIN y 21287 | (10) Ereekponts rca alone cr wi
© E aruanate ae based on 8 icarolin dosage
5 H ragmen of at least 3 g administered every
2 i i i on
3 CEPHENS (PARENTERAL) (neluding cephalosporins |, and WV. Pla sary)
À re Cotasame! Du DB I IE el ES MR: 332] Wi Breakports are based on 8 dosage
H rogmen of g admnstored every hor? 9
H administered every 8h
CN O we E TS E TEN À 232 | (12) Breskporis are based on a dosage
i H regmen of g dmnstered every Shor 29
E i administered even 12h
Me | Cerda Wig [a Aa | à À 216 | (13) Brccipons are basod ona dosage
i i fegmen of? 9 every & administered over
i H oh
MONOBACTANS
6 | rem we | ee] ET | © mer 332 | (1a) Breakpors are based on a dosago
a H regmen of 9 aamnistered every 6 or 2 g
a i imnisered every 8h
E
B IE
: E

Table 28-1

Pseudomonas aeruginosa
‘M02 and MO7

Table 28-1

Pseudomonas aeruginosa
‘M02 and Mo?

3: Table 28-1. Pseudomonas aeruginosa (Continued) iS
: Tnterprative Categories and] — Interpretive Categories and 3
: Zone Diameter Breakpoints, MIC Breakpoints, 3
TestReport | Antimieroblal Disk nearest whole mm voit A
3 Group Agent content | 85 | 1 TR El TR Comments E
: CRRSAPENENS. £
B 6 | Donpenem Top ES EN [2 | 28 — | (16) Breakpains for donpenem are based on

S dosage ragmen of 00 mg administered
E seen

8 | imipenem tong | 219 im À sis | cof 4% À 2e |'t61éresipoits tormpenem are based on a
dosage regimen af g administered every 8h
F600 mg administered every 6

a pu 1049 219 18n : 515 <2 y 28 | (17) Breakpoints for meropenem are based on
8 dosage regimen of | 9 adminstered every
En

TPOPEPTIOES

(18) WARNING: Clinical and PK-PD data demonstrate colistin and polymyxin 8 have limited clinical eficacy, even if an intermediate result Is obtained. Alternative

agents are strongly preferred. Colistin and polymyxin B should be used in combinat ‘or more active antimicrobial agents. Consultation with an infectious,
diseases specialist is recommended.

A © |Coisimor = = = = = = T4 | (19) Colistn (meihanesuifonate) should be

: polymyin 8 - 2 z - - s2 54 | given with a loading dose and maximum

Tenally adjusted doses (see International

Consensus Guidelines‘).

(20) Polymyxin 8 should be given with a
loading dose and maximum recommended
doses (see Intemational Consensus
Guidelines‘)

(21) When colistin or polymyxin B is given
systemically, nether ls likely to be
effective for pneumonl

(22) For colistin, broth microdilution,
: CBDE, and CAT MIC methods are

acceptable. For polymyxin 8, broth
microdilution is the only approved method,
Disk diftusion and gradient difusion.
methode should not be performed (e
Table 0)

Pautasas BU LIV PU PHPUIS COROT PMO PUIS

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£ ! Table 2B-1. Pseudomonas aeruginosa (Continued) El
$: interpretvo Calegores and | Interratve Categories and a
5: Zone MIC Breakpoints, €
di TestRaport Disk mt. 2
A ‘Group content [8 5 ü E Comments 2
3 ANINOGLYEOSIDES Fi
À | Oertamen Tug PRA a A 5m E
À Totramjan doy pes paar a ii Fi
3 8 [Amiaon 3oug [st fet IET ae E
5: o—[Nstimen Song CE EE Een; 22 E
2: FLUOROGUNOLONES
E: © | Cpofoan O EE | em ETS 32 | (8 Breokpomnis are based ono dosage
HE i : i Fogmen of 400 mg V admnstored every 8h
y: 8 [retos 50 [iaa |e; 27 | 24 | 24) Emaiçonts aro based ona dosage
regimen of 750 mg administered every
ES ban
E: O mos | SE A 38 | (95) Fortesing ond eporing ofunmary wack
8: Slats ony
5 © | Weroraein is [am | a 3 316 _| See comment (5),
& 9] otoan sw | 216 RA El
È 0 | EGG TEE: HEC ET EL El
= ‘Abbreviations: ATCO®, American Type Culture Callechen; CAMHE, cation-adusted Mueller Hinton broth; CAT, colistin agar test; CBDE, colistin broth disk
El elution; I, intermediate; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; PK-PD, pharmacokinetic-pharmacodynamic; QC, quality control:
El R resistant, susceptible.
El
Es Footnote
a. ATCO®is a registered trademark ofthe American Type Culture Collection.
References for Table 28-1
Y Hackel MA, Tsuji M, Yamono Y, Echols R, Karlowsky JA, Sahm DF. Reproducibility of broth microdilution MCs for the novel siderophore
cephalosporin, cefiderocol, determined using iron-depleted cation-adjusted Mueller-Hinton broth. Diagn Microbiol Infect Dis. 2019:94(8):321-325.
2 CLSI. Performance Standards for Antimicrobial Disk Susceptibilty Tests. 13th ed. CLSI standard MO2. Wayne, PA: Clinical and Laboratory Standards
Institute; 2018.
3 GLSL #02 Disk Difusion Reading Guide, 1st ed. CLS! quick guide MO20G. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
© £ Tsul BT, Pogue JM Zavaxcki AP, et al. Intemational consensus guidelines for the optimal use of the polymyxins: endorsed by the American
College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMD), Infectious Diseases Society of E
: America (IDSA), Intemational Society for Antinfective Pharmacology (SAP), Society of Critical Care Medicine (SCCM, and Society of Infectious 3
: Diseases Pharmacists (SIDP). Pharmacotherapy. 2019;39(1):10-39. 8
: E

Table 28-1

Pseudomonas aeruginosa
‘M02 and MO7

ov

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Table 28-2

‘Acinetobacter spp.
‘Mo2 and Mo?

Table 2B-2. Zone Diameter and MIC Breakpoints for Acinetobacter spp.

Testing Conditions Routine QC Recommendations (see Tables 44-1 and 54-1 for acceptable
QC ranges)

‘Medium: — Disk difusion: MHA.
Broth dilution: CAMHB; iron-depleted CAMHB for Escherichia coli ATCC® 25922 (for tetracyclines and trimethoprim
‘ceflderocol (see Appendix I)" sulfamethoxazole)
Agar dilution: MHA Pseudomonas aeruginosa ATCC® 27853

Inoculum: Broth culture method or colony suspension, equivalent to a | | Refer to Tables 44-2 and 542 to select strains for routine QC of factam
0.5 McFarland standard combination agents.

Incubation: 35°C+2°C; ambient air; 20-24 hours, all methods When a commercial test system is used for susceptibility testing, refer to the

‘manufacturer's instructions for QC test recommendations and QC ranges.

General Comment

(1) For disk diffusion, test a maximum of 12 disks on a 180-mm plate and no more than 6 disks on a 100-mm plate; disks should be placed no less than 24 mm
apart, center to center (see MOZ, Subchapter 3.6). Each zone diameter should be clearly measurable; overlapping zones prevent accurate measurement,
Measure the diameter of the zones of complete inhibition (as judged by the unsided eye), including the dameter ofthe disk (see the M02 Disk Diffusion
Reading Guide). Hold the Pet pate afew inches above a black background iluminated with reflected light. The zone margin should be considered the area
showing no obvious, visible growth that can be detected with the unaided eye. Ignore faint growth of tiny colonies that can be detected only with a magnifying
lens at the edge ofthe zone of inhibited growth. With timethoprim and the sulfonamides, antagonist in the medium may allow some sight growth; therefore,
disregard sight growth (20% or less ofthe lawn of growth) and measure the more obvious margin to determine the zone

NOTE: Information in boldface type is new or modified since the previous edition.

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8 Table 2B-2. Acinetobacter spp. (Continued) El
E Interpreive Categories El
E and €
& Interpretive Categories and 2
al MIC Breakpoins, E
SE | resrepor | Antinicrobi! bi vom. E
2 ‘Group Agent Content 3 1 R Comments E
PENCIL 8
© [Prenom Mon [enim iso] em; e pen E
3 FLACTAN COMBINATION AGENTS $
& À [Ampriinsubadan [100g Jesica is | ed 108 23208
E S| Pipersctintacobactam | 10010 uq | 2211 18:20 1617 | cto | MAR} ana
‘| EE RE EE ST
‘GEPHENS (PARENTERAL) (including cephalosporins ossary)
= À | Cotandme 0 yg se ES]
È 5] Cefepime sou EC ni 22
E B Cefotaxne E] <8 16-37 E]
5 8 |cermaano 3049 ss its | 2e
E in] Cofcerocot Er] al 1216 | (9) Breaipans wre based ona dosageregman
à | É 4 S12 gevery Sh asmnisered ver >
€ CARBAPENENS
5 À) Donponem Tore 22 I Je | Eragon fordarpenom are Based ona
2 dosage regimen of 500 mg administered every
3 : sn
El a | mpe ton a | 4 =
& {4)Breaiponts forimpenem are based on a
dosage regmon of 500 mg administered every
on
A | Merepenem tou | ir 2 4 28 | B)Eroaipaints for meropenem ar based on a
i i i dosage regmen of 1 g adminsereg every 8 hor
E | | | 500 mg administered every on.
E
t IE
: E

Table 28-2

Acinetobacter spp.
‘M02 and MO?

Table 28-2

‘Acinetobacter spp.
‘Mo2 and Mo?

&: Table 2B-2. Acinetobacter spp. (Continued) =
À Interpretive Categories E
5 and a
Zone Diamster Interprete Categories and 2
MIC Breakpoints, E
TestReport Disk gin E
Group Content 5 f E Comments
TPOPEPTIDES

(6) WARNING: Clinical and PK-PD data demonstrate colstin and polymyxin B have limited clinical efficacy, even if an Intermediate result is obtained. Alternative
are strongly preferred. Colistin and polymyxin B should be used in combination with one or more active antimicrobial agente. Consultation with an infectious di
‘specialist is recommended.
© | Colstn oF - - = :-|- 2 34 |) Colistn (methanesuifonate) should be given
polymyxin 8 - - - is] - 2 24 | witha loading dose and maximum renally
adjusted doses (see International Consensus

(8) Polymyxin B should be given with a loading
dose and maximum recommended doses (
International Consensus Guidelines‘).

(9) When colistin or polymyxin Bis given
systemically, the drug is unlikely to be effective
for pneumoni

(10) The only approved MIC method is broth
‘microdilution, CBDE, CAT, disk diffusion, and
Gradient difusion should not be performed,

111) Apples to A Baumanni complex on

AMNOGLYCOSIDES
À

$

3

3

z

5 A ratones To | si Tun E CO

2 E “Amikacin 30ug 217 15-16 7 <14 $16 32 HET

El © | Netimiein = — — EN 1 ES]

gi TETRACYCLINES

À 2 | enormes tata auto tar are alo conser susp to donne and mince, Homer, sameeren th ae itemedt or stant

5 tetona maybe susceptbi to doxyeyine, mnacycine o boh

El CESTO Son en Dome] = | s jee E
Fa [inosine un ete ten) «+ ee El
8: 0 reingyeine 30.9 ES su CE E
$: FLUOROGUINOLONES: 2
a: À | Cpntosen m ET Ha. 2 El E
E: A | cotos sua | str ite | o 4 E] 2
Fi D Tositorsen Er sig) ir pew [ep ti El $
$: É
A E

PEMOIE OU St DULBUS JLOMIDU 40 VONEDHKINP POZUOLINBUN "0202/62/10 - GB - MEN PUBUEMAQ - 35499 ISTO

8: Table 28-2. Acinetobacter spp. (Continued) El
8: Interpretive Categories El
sl and €
à: Zone Diam Interpretive Categories and 2
A Breskpoints, Mic Breakpoins, El
E Testrteport | Antimicrobial Disk nearest whole m vim E
Group Agent content [TOTES 1 E Comments E
FOLATE PATHWAY ANTAGONISTS 2
E © | Tamemopam- 13057849] 210 ] Mel; em — | ES
Sullamethoxazole E H E El
3 2 Ablreviations: ATCC®, American Type Culture Collection; CAMAS, calion-adusted Musller Hinton breih; CAT, colistin agar test; CBDE, colisin broth elution 3
g: test; |, intermediate; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; PK-PD, pharmacokinetic-pharmacodynamic; QC, quality control;
À ! Reresistant;S, susceptible.
& Footnote
Ê: a. ATCOPis a registered trademark of the American Type Culture Collection.
= References for Table 28-2
E | Hackel MA, Tsuji M, Yamono Y, Echols R, Karlowsky JA, Sahm DF. Reproducibility of broth microdilution MCs for the novel siderophore
= cephalosporin, cefiderocol, determined using iron-depleted cation-adjusted Mueller-Hinton broth. Diagn Microbiol infect Dis, 2019;94(8):321-325,
Bi 2 CLS, Performance Standards for Antimicrobial Disk Susceptbity Tests. 13th ed. CLSI standard MO2. Wayne, PA: Clinical and Laboratory Standards
El Institute; 2018.
A
3 GLSL #02 Disk Difusion Reading Guide. 1st ed. CLSI quick guide MO20G. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
+ Tsuji BT, Pogue JM Zavaxck AP, et al International consensus guidelines for the optimal use of the polymyxins: endorsed by the American
College of Clinical Pharmacy (ACCP), European Society of Clinical Microbiology and Infectious Diseases (ESCMD), Infectious Diseases Society of
America (IDSA), Intemational Society for Antiinfective Pharmacology (ISAP), Society of Critical Care Medicine (SCCM), and Society of Infectious
Diseases Pharmacists (SIDP). Pharmacotherapy. 2019:39(1):10-39.
: E
: E

Table 28-2

‘Acinetobacter spp.
"MOZ and MO?

os

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Table 28-3

‘Burkholderia cepacia complex
‘M02 and MO7

Table 2B-3. Zone Diameter and MIC Breakpoints for Burkholderia cepacia complex

Testing Conditions

Medium: Disk diffusion: MHA
Broth dilution: CAMHB
‘Agar dilution: MHA
Inoculum: Broth culture method or colony suspension, equivalent to a
0.5 McFarland standard

Incubation: 35°C+2°C; ambient air; 20-24 hours, all methods

Routine QC Recommendations (see Tables 44-1 and SA-1 for acceptable
QC ranges)

Escherichia coli ATCC® 25822 (for chloramphenicol, minocycline, and
timethoprim-sulfamethoxazole)
Pseudomonas aeruginosa ATCC® 27853

Refer to Tables 44-2 and SA-2 to select strains for routine QC of F-lactam
combination agents.

When a commercial test system is used for susceptibilty testing, refer to the
‘manufacturer's instructions for QC test recommendations and QC ranges.

General Comment

(1) For isk difusion, test a maximum of 12 disks on a 150-mm plate and no more than 6 disks on a 100-mm plate; disks should be placed no less than 24 mm
apart, center to center (see M02," Subchapter 3.6). Each zone diameter should be clearly measurable; overlapping zones prevent accurate measurement,
Measure the diameter of the zones of complete inhibition (as judged by the unaided eye) including the diameter of the disk (see the M02 Disk Difusion
Reading Guide). Hold the Pet plate a few inches above a black background iluminated with reflected light. The zone margin should be considered the area
showing no obvious, visible growth that can be detected with the unaided eye. Ignore faint growth of tiny colonies that can be detected only with a magnifying

lens at the edge of the zone of inhibited growth. With trimeth opr

and the sulfonamides, antagonists

the medium may allow some slight growth; therefore,

disregard slight growth (20% or less of the lawn of growth) and measure the more obvious margin to determine the zone diameter,

NOTE: Information in boldface type is new or modified since the previous edition

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Is

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Table 2B-3. Burkholderia cepacia complex (Continued)

Interpretive Categories and
Zone Diameter Interpretive Categories and MIC
Breakpoints, Breakpoints,
nearest whale mm volt
Testreport | Antimicrobial Disk
Group Agent Content | s ir ion Comments
EACTAN COMBINATION AGENTS
[ecocetin canasto] T T Ran En]
PRES (PARENTERAL) go Land Y Pease eerie Gos
© | Cetaziame Ta 7 >21 Le | OL
TARBAPENENS
A| woropenom [iow Lam | wo sis] a 5 | m]
TETRACYELINES
© [umo la Low Le js [ a CE |
FLUOROQUNOLONES
À [ Lovotorasn DT] 0; 0 D CI
FOUATE PATHWAY ANTAGONISTS
A| Temetnopnm- TEST | 215 = DEL
Süamenoxazci. i
PHENCOLS
CN CRraRPRaRTEST a a = ls TS] 232 | O Not rouinely reported on solates Fom Mo
nary tact,

‘Abbreviations: ATCE® American Type Culture Collecion; CAE, cation adjustod Mueller Hinton broth | intermediate; MHA Mueller-Hinton agar; MC, minimal

inhibitory concentration; QC, quality control; R, resistant; S, susceptible,

Footnote
a. ATCCP is a registered trademark of the American Type Culture Collection
References for Table 28-3

1 CLSI. Performance Standards for Antimicrobial Disk Susceptiblty Tests. 13th ed. CLSI standard MO2. Wayne, PA: Clinical and Laboratory Standards
Institute; 2018.

2 CLSL M2 Disk Difusion Reading Guide. 1st ed. CLSI quick guide MOZQG. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

Table 28-3

‘Burkholderia cepacia complex
‘M02 and MO7

ONPE CONTIN STO

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Table 28-4

Stenotrophomonas maltophilia
‘o2 and MO7

8: Table 2B-4. Zone Diameter and MIC Breakpoints for Stenotrophomonas maltophilia =
: 3
B Testing Conditions Routine QG Recommendations (see Tables 4A-1 and SA-1 for acceptable E
B GG ranges) E
: Medium: Disk fusion: MHA E
: Broth dilution: CAMHB; iron-depleted CANHB for Escherichia coli ATCC® 25922 (for chloramphenicol, minocycline, and
i cefiderocol (see Appendix D! trimethoprim-sulfamethoxazole)

Pseudomonas aeruginosa ATCC® 27853
Agar dilution: MHA
Refer to Tables 44-2 and 5A-2 to select strains for routine QC of B-lactam
Inoculum: Broth culture method or colony suspension, equivalent to a | | combination agents.
05 McFarland standard

When a commercial test system is used for susceptibilty testing. refer to the
Incubation: 35°C+2°C; ambient air; 20-24 hours, all methods ‘manufacturer's instructions for QC test recommendations and QC ranges.

General Comment

(1), For disk diffusion, test a maximum of 12 disks on a 150-mm plate and no more than 6 disks on a 100-mm plate; disks should be placed no less than 24 mm
apart, center to center (see MO2,? Subchapter 3.6). Each zone ciameter should be clearly measurable; overlapping zones prevent accurate measurement,
Measure the diameter of the zones of complete inhibition (as judged by the unaided eye), including the diameter of the disk (see the M02 Disk Diffusion
Reading Guides). Hold the Pet plate a few inches above a black background iluminated with reflected light. The zone margin should be considered the area
showing no obvious, visible growth that can be detected with the unaided eye. Ignore faint growth of tiny colonies that can be detected only with a magnifying

! lens at the edge of the zone of inhibited growth. With trimethoprim and the sulfonamides, antagonists in the medium may allow some slight growth; therefore,

À disregard sight growth (20% or less ofthe lawn of growth) and measure the more obvious margin to determine the zone diameter.

NOTE: Information in boldface type is new or modified since the previous edition

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g: Table 2B-4. Stenotrophomonas maltophilia (Continued) 3
8: Interpretive Categories a
sl and €
a: Zone Diameter Interpretive Categories and MIC 2
A Breakpoints, Breakpoints, El
3 TestReport Antimicrobial Disk nearest whole mm voit Fi
Group ‘Agent Content | 8! 1 ie | s! a Comments E
ELACTAN COMBINATION AGENTS Fi
N al oran Gent | —— stent Sam ; 2107 | E
S: CEPHENS (PARENTERAL) (Including cephalosporins LI, sear) El
2: © | Cotazidme 3 fe E
8: a] Cofemeel ET 4 {8 | 216 | @2yBrearponts are based on a dosage
: regimen 012.9 every 8h administered over
: i i i on
TETRACYGUNES
E À [rooms [29 [mi se [ee] a} + 36 |
B: FLUOROQUINOLONES
= A [tevotoreen As ais a a; ]
= FOLATE PATHWAY ANTAGONISTS
E À | Tnmetnopnm- TTS ET ESE
E sutamethorazola fr i i i i
= PHENICOLS
5 © | CHoramphencol = a E E G) Not routinely reported on soates rom
‘ho unnary tract
El Abbreviations: ATCO American Type Culture Collection; CANHE, cation aqusted Mueller-Hinton broth; I, intermediate; MHA, Mueller-Hinton agar; MIC, minimal
E inhibitory concentration; QC, quality control R, resistant; S, susceptible
Footnote
a. ATOO®is a registered trademark of the American Type Culture Collection
References for Table 28-4
Y Hackel MA, Tsujl M, Yamono Y, Echols R, Karlowsky JA, Sahm DF. Reproducibility of broth microdilution MCs for the novel siderophore
cephalosporin, cefiderocol, determined using iron-depleted cation-adjusted Mueller-Hinton broth, Diagn Microbiol Infect Dis. 2019:94(4):321-325.
2 GLSI. Performance Standards for Antimicrobial Disk Susceptiblty Tests. 13th ed. CLSI standard MO2. Wayne, PA: Clinical and Laboratory Standards
Institute; 2018.
3 ELSI. M2 Disk Diffusion Reading Guide. 1st ed. CLSI quick guide MO2QG. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
E

Table 28-4

Stenotrophomonas maltophilia
‘M02 and MO7

Table 28-5
Other Non-Enterobacterales.

Y: Table 2B-5. MIC Breakpoints for Other Non-Enterobacterales (Refer to General Comment 1) =
: 3
B Testing Conditions Routine QC Recommendations (see Table 54-1 for acceptable QC ranges) E
: Medium: Broth diution: CAMHB Escherichia col ATCC™ 25922 (for chloramphenicol, tetracyclines, E
x ‘Agar ion: MHA, sulfonamides, and timethoprim-sulfamethoxazole)
i Pseudomonas aeruginosa ATCC? 27853
À Inoculum: Broth culture method or colony suspension, equivalent to a
; 0.5 MeFarland standard Refer to Tables 4A-2 and SA-2 to select strains for routine QC of lactam
combination agents.
Incubation: 35'C42"C; ambient ai; 16-20 hours
A When a commercial test system is used for susceptibility testing, refer to the
i manufacturers instruction for QC test recommendations and QC ranges.
General Comments
: (1) Other non-Enterobacterales include Pseudomonas spp. and other nonfastidious, glucose-nonfermenting, gram-negative bacili but exclude P. aeruginosa,
4 Acinetobacter spp., B. cepacia complex, and S. matophila (refer to Tables 28-2, 28-3, and 2B-4, respectively). Recommendations for testing and
8 : reporting re hydrophila complex, Burkholderia mallei, Burkholderia pseudomallei, and Vibrio spp. (including V. cholerae) are found in CLSI
: document MS."
À © @) For other non-Enterobacterales, the disk difusion method has not been systematically studied. Therefore, for his organism group, disk diffusion testing is
i not recommended.
Ñ NOTE: Information in boldface type is new or modified since the previous econ
8:
2;
8:
E: A
El El
de
3: El
a: 2
8: 8
ae E
a: E
Ri E

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ae Table 2B-5. Other Non-Enterobacterales (Continued) 3
8: interpretive Categories and | Inerpraive Categories and WIC El
E Zone Diameter Breakpoints, Breakin €
gi ‘Group Agent coment | s iets ia Comments E
: PENICILUNS. E
: © Trier EI as ES = ESTAS CIT | 2
[BLACTAM COMBINATION AGENTS E
5 ©] Pipemelintazobedam = = T= NINE El
pl 0 —[icarein-devuanate = : = STEREO pa
@: tretang eMpoTRaTL in
: À | Conaname = <3 5 E
El : ET Colomo = E © 322
: c tana = set ear Te
E E |cormacne = So [tes | zu
8: O | Celoperezons = 07 2 Tao
8: 0 | Cotizoxme = se À 1692 ze
: Oo | Hoxaiactam = soi tes | se
E MONOSACTANS
E E [Ever = O EN >» |
= TARBAPENENS
E © | impenem = => >- Tar os | ne
E ©] Heropenem = a = 2m)
3: ANMNOGIYCOSIDES
ES À | Gentomen, = = = Fa 3 En
: A Tobramyeia = = = ET E 210
: ©] Amiiaon S ESO DECIS ICI SAR
: 0° TE = = = EE 22
TETRACYCLINES
: (8) Organisms that re susceptible to letracycine are also considered susceptible to doxycycine and minocycine, However, some organisms tht are intermediate or resistant to
! tatracydno may be suscapubl o doxyeycine, minaeycine,orboin
E Y] Tevasyaine = CH — Fa i En
2 0 Boxyeycine = == [sa E 216
©] inosyeine = = = ET i 18
: FLUOROGUNIOLON
: © | Cproforacn - > = = E 7 1 34
: 8 |iootoen = = 22 4 25
: ©] Gatitorecn = = te ats
5 9 —Tiometoxaca = = == ais
a O | Nortfoxacin = = sa 82s For testing and reporting of urn z
E i i Aract isolates only. E
A 5 [ofen = EE AE I TE |8
: E

Table 28-5

Other Non-Enterobacterales
‚Mor.

9s

“pas SISI [IF “IAS SPIDPUDIS CLORIOGPT PLO PUIS

Table 2B-5. Other Non-Enterobacterales (Continued)

Table 28-5
Other Non-Enterobs
MO7

acterales

Interpretive Categories and
Zone Diameter Breakpoints,

Taterprative Categories and
MIC Breakpoints,

TestReport Antimicrobial Disk est whole mm mom

‘Group Agent. Content | s 1 els 1 R Comments
FOLATE PATHWAY ANTAGONISTS

e methogrim = = ee = La

Sufemeihoxazcie i
y Sulfonamides = 5 = (= = 2512 |E)Sufsoxazole an be used To represent any
ofthe curenty avaiable sufonemide
i preparations

PHENICOLS

© | CHloramphenioa = = = =] 88 {| 16} 282 | (@)Notroutnely reported on selates from the

urnarytract

Abtreviatons: ATCO American Type Cuire Colecton, CAMAS, can «dusted Male into Bro fem

inhibitory concentration; QC, quality cont

resistant; S, susceptible,

Footnote

a, ATCC®is a registered trademark of the American Type Culture Collection

Reference for Table 28-5

jate; MHA, Mueller-Hinton a

MIC, minimal

Y GLSL Methods for Antimicrobial Dilution and Disk Susceptiblty Testing of Infrequenty Isolated or Fastdious Bacteria. 3rd ed. CLSI guideline MAS.
Wayne, PA: Clinical and Laboratory Standards Institute; 2016,

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For Use With MO2 and MO7

‘M100, 30th ed

This page is intentionally left blank.

Clinical and Laboratory Standards Institute. All rights reserved.

37

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Table 2C

Staphylococcus spp.
102 and MO7

Table 2C. Zone Diameter and MIC Breakpoints for Staphylococcus spp.

Testing Conditions Routine QC Recommendations (see Tables 4A-1 and SA+1 for acceptable
OC ranges)
Medium: — Disk fusion: MHA
Broth ution: CAMHB; CAMHB +2% NaCl for oxacilin; Disk difusion:
CAMHB supplementedto 60 ug/n calcium for daptomycin. | | S. aureus ATCO™ 25923
‘Agar dilution: MHA; MHA + 2% NaC! for oxacilin
NOTE: Agar diution has not been validated for daptomyein. Dilution methods:
Inoculum: Colony suspension, equivalent o a 0.5 MeFarland $. aureus ATCC®29213
standard
Incubation: 35°C+ 2°C; ambient ar Refer to Tables 4A-2 and 5A-2 to select strains for routine QC of
Disk difusion: 16-18 hours; 24 hours (for cefoxitin when fHactam combination agents.
testing Staphylococcus spp., excluding S. aureus,
$. lugdunensis, S. pseudintermedius, and S. schleifen) When a commercial test system is used for susceptibility testing, refer to the
Dilution methods: 16-20 hours; 24 hours for oxacilin and manufacturer instructions for QC test recommendations and QC ranges.
Testing at temperatures above 35°C may not detect
methicilin (oxacillin)-esistant staphylococci (MRS).
General Comments
(1) For isk difusion test a maximum of 12 disks on a 150mm plate and no more than 6 isks on a 100-mm plate; disks should be placed no less than 24 mm

apart, center to center (see M02,' Subchapter 3.6). Each zone diameter should be clearly measurable; overlapping zones prevent accurate measurement.
Measure the diameter of the zones of complete inhibition (as judged by the unaided eye), including the diameter of the disk (see the M02 Disk Diffusion
Reading Guide’). Hold the Peti plate a few inches above a black background illuminated with reflected light, except for linezolid, which should be read with
transmitted light (plate held up to light source). The zone margin should be considered the area showing no obvious, visible growth that can be detected with
the unaided eye. Ignore faint growth of tiny colonies that can be detected only with a magnifying lens at the edge of the zone of inhibited growth. With
trimethoprim and the sulfonamides, antagonists in the medium may allow some slight growth; therefore, disregard slight growth (20% or less of the lawn of
growth) and measure the more obvious margin to determine the zone diameter. For linezolid, any discemible growth within the zone of inhibition is indicative
of resistance to the respective agent.

(2) For staphylococci when testing chloramphenicol, clindamycin, erythromycin, Iinezoid,tecizolid, and tetracycline by broth microdilution MIC, traling growth can
make end-point determination dificult. In such cases, read the MIC at the lowest concentration where the taling begins. Tiny buttons of growth should be
ignored (see MOT Figures 3 and 4). Wih trimethoprim and the sulfonamides, antagonists in the medium may allow some sight growth; therefore, read the
end point at the concentration in which there is> 80% reduction in growth compared with the control (see MO7, Figure 5)

(3) Routine testing of urine isolates of Staphylococcus saprophyticus is not advised, because infections respond to concentrations achieved in urine of
antimicrobial agents commonly used to treat acute, uncomplicated UTIs (eg, nitrofurantoin,trimethoprim + sulfamethoxazole, or a fluoroquinolone).

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Fi Table 2C. Staphylococcus spp. (Continued) El
E <
E (4) Historical, resistance to the penilinasetatie penclins (see Glossary ) has been refered toas “methcilin resistance” or "oral resistance.” MRSA E
ES are strains of S. aureus that express mecA, mecC, or another mechanism of methicilin (oxacillin) resistance, such as changes in affnity of penicilin-binding 2
E Pate oc es à ses ce d
È (6) Most methicilin (oxailin) resistance is meciated by meca, encoding PBP2a (also called PBP2). Isolates that test positive for mecA or PBP2a should be 8
$ reported as methiiln (oxacilin resistant (see Appendix H) E
S: Detection of methiclin (sxaclin) resistance in staphylococci is achieved by using specific methods as listed in Table 2C and futher described in Table F. 8
e:
si Methods for Detection of Methicilin (Oxacilin)-Resistant Staphylococcus spp.
8: Cefoxin disk ‘Oxacilin disk
organism Cefoxtin me fusion oxacilinmc fusion úOxacilin salt agar
E ame Yes Yes Yes No Yes
E 16-20) (16-48 1) aan gan
E Yes Yes Yes No No
= Snakes (16-20 my (6-18) ean
5 Fe No Yes Yes Yes No
a: pier (16-18 1) any (15-18 »)
4 No No Yes Yes No
E [ema din
E: No No Yes Yes No
2 Sete [20 (16-181)
a ‘Other Staphylococcus spp. No Yes Yes” No No
(not isted above) gan an
Abbreviations: h, hour(s); MIC, minimal inhibitory concentration; MRS, methicillin (oxacillin)-resistant staphylococci; PBP2a, penicillin-binding
protein Za.
3 For isolates of “other Staphylococcus spp.” from serious infections for which the oxacillin MICs are 0.5-2 g/mL, testing for mecA or PBP2a
should be considered see comment [17). cefoxitin disk difusion Is nat currently recommended.
rare and include a novel mecA homologue, mecC.* MICs for strains with mecC are
‘yplalycefoxtin resistant and oxaclin susceptible; mec resistance cannot be detected by tests drected at meca or PEP2a,

(6) MRS, as defined by cefoxitin or oxacillin testing, as appropriate to the species, are considered resistant to other f-lactam agents, ie, penicillins, f-lactam
combination agents, cephems (with the exception of cefarolne), and carbapenems. This is because most cases of documented MRS infections have
responded poorly to fractam therapy or because convincing cinical data that document clica sficacy for those agents have not been presented

3 (7) For tests for B-lactamase production, methicillin (oxacillin) resistance and mecA-mediated methicillin (oxacillin) resistance using cefoxitin, reduced
Suscopibity to vancomyeln, ICR, and highievel muprocn resistance (S. aursus ony), refer to Tables JE, 3F, 16, 3H, and A respectively. E

B NOTE: Information in boldface type is new or modified since the previous edition. 2

: Ea

Table 2c

Staphylococcus spp.
‘02 and MO7

09

“pas SISI [IV “IAS SPIDPUDIS CLORIOGPT UD PUIS

Table 2C

Staphylococcus spp.
102 and MO7

Table 2C. Staphylococeus spp. (Continued)

Inierpreive Categories and | Interpretive Categories and
Staphylococcus "MIC Breakpoints,

Test Report | Antimicrobial spp. Disk i

‘Group. Agent Indications | Content SSD TIR Comments.

PENICILLINASEABILE PENICILLINS

(8) Peniciin-suscapttis stophylococe are susceptible to other £-aclam agents with established cinicaleffcacy for staphylococcal infections (Includng both peniciinase-abile and
Peniclinase-stale agents, see Glossar 1} Peniclinesistant staphylococci ae resistant to pericilinase-abile peniclns

(9) Peniclin should be used to test the susceptibilty of all staphylococci to peniclinaseable peniclins (see Glossary |), Peniciinresistart strains of staph/ococci produce

lactamase. Perform a tests) to detect f-actamase production on staphylococa for which the peniclhn MICs are <0.12 ygimL or zone diameters 229 mm before reporting the isolate

85 peniilin susceptible. Rare isolates of staphylococe that contain genes for lactamase production may appear negative by lactamase tests, Consequerly, for serous infections

requring peniclin therapy, laboratories should perform MIC tests and P-lactamase testing on all subsequent isolates rom the same patent. PCR testing ofthe isolate forthe DZ.
lactamase gene maybe considered. See Tables 2D and3E

A | Peniailin Alstaphyfococa | 10unts [2287 = } = 228180127 | = 1202 | (10) Formethiellin recent
staphylococa, report ponlin as
resistant or do not report

PENICILUINASESTABLE PENICILLIN

(1) Cofoxt tested as a surogate for oxacilin for some spaces of Staphylococcus. Isolates that st resistant by cefoxtin or oracilin, when using the appropriate test method for
the species, shoul be reported as methleilin (oxaciln) resistant. testing only cefoxtin, report as methielin (oxaclin) susceptible or resistant based onthe cefoxtin result Isolates
that test other mecA negative or PBP2a negative or cofoxlin susceptible should be reported as methleilin (oxaciin) susceptible

(12) Oxeciin (or cefoxin) results can be applied to the other penialinase-stble penicilins coxacilin, icoxacilin, methialin, and alolin) For agents with established cnica!
ficacy and considering ste of infection and appropriate dosing, methlelin(oxaclin}-susceptble staphyococs can be considered susceptible to.

‘© lactam combination agerts (amoxiili-lavulanate, ampiilin-sulbactam, pperacilintazobactam)

+ Oral caphams (cafaeor, cee, cephalexin, cefpedoxime, cefprozl cefuroxime, lracarber)

+ Parenteralcephems including cephalosporins | I Il, and IV (cefamandole, cefazolin, cefepime, cefmetazole,cefonii, cafoperazone, cefotaxime, cefoetan, caizoxime,
Catiiaxone, cefuroxime, catoine, moxalactam)

+ _ Carbapenems (dorpenem, ertapenem, imipenem, meropenem)

Methicitin(ocacilin)-esistant staphyfococc! are resistant to all curentiy avalable f-lactam antimicrobial agents, withthe exception of osfarline. Thus, susceptibility or resistance to
wide array of Pactam antimicrobial agents may be deduced from testing only penclin and ether cofoxtin or oxaclin. Testing of other lactam agents, except cefarlina, i not
‘advised. See general comments (5) and (6).

Adtional explanation onthe use of cefoxiin for prediction of mecá-medated methicillin (oxacilin) resistance can be found in Subchapter 3.12 of MO and Subchapter 3.9 of MO2*

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Fi Table 2C. Staphylococcus spp. (Continued) El
E El
& Test Staphylococcus 2
3 Report) Antimicrobial spp Disk a a ES
a (Groupl_" Agent indications _| Content si so iii 8 Comments E
PENICILLNASE-STÄBLE PENICILLINS (Coninued) 3
: À [Own | S aurusans = | on — 2 LL, (18) Groalin ask testing isnot E
5 lugdunensis i (satin) ON | alae Saurus on a
i iG nero
3 i i &
ES | 4 I ge (14) Forisoltes ofS aureus
E: {hat do nt gow wel on
y i I CALE or unsupplemented
: 2049 zm iio jos sa À - f= | 28 | Mito smat-catony
calor (esfoxtny (cetoxi) | vanne testing on ober
È {Surogate meda (ep, EMMA) does not
E test for rolabiy die mec madiated
E oraclin) ii E resistance, Testing tr PEP2
5 using duced gro (o
FS pod ¿ pd grova taken from the zone
> ; margn surrounding acefoxtin
E pod : : disk on her BMA or a blood
= io Poi agar plate afer 26 ours
E incubaion in 5% CO) oF mec
E : : Shad be cone
3
E po odo See general comments 5) ond
(@) ona comments (3), (17,
i i i and (12
A EE EC ET] ET anna] See genera comments eyed
oracuin | (oxactiny | toxsctim) | xectiny (oxacitn | (Gand eomments (8). (1)
vo DE and)
2099 as ii sm = 102 5252 | ts) cotoxin mctesting is
: colon | (estoutn) (extoxtin no retablo for detecing mect-
(Surogate ; i gd medita resistance in
tester S'epdermais
exact
5 IT ae tete Tea te a er ator TC nar
sscutintermedivs | orasıim cefoxitin disk tests re reidble
and 5. sente Po Poi 1 iin pecá mesitas
resistance n
| 4 E: Dooudintermedivs and 5.
i i Schoen e
: i Id Seo general comments (5) and E
: (6) and comments (3) (17), le
: | Le andit2 3

Table 2c

Staphylococcus spp.
‘02 and MO7

“pas SISI [IF “IAS SPIDPUDIS CLORIOGPT PLO PUIS

Table 2C. Staphylococcus spp. (Continued)

Table 2C

Staphylococcus spp.
02 and MO7

Interpretive Categories and
MIC Breakpoints,

Tew Staphylococcus git Comments
[Report Antimicrobial app. Disk 7
¡Group! _ Agent Indications _| Content s R sisi! R

PEMCILLINASE STABLE PENICILLINS (Continued)

À | Oxeciin | Other 3049 25 - sm ETE 1 (7) Oxacilin WIC breakpoints
Staphylococcus | cofoutn | (cofoxtin) : (cofoxtin) | (oxaciin) i may overcal resistance, and
spp.oxcuang | (surrogate some isolates for which the
S aureus test for A A A xacilin MICs are 05-2 ugimt,
$ lugdunensis | oxaciin) may be mecA negative. Isolate
S epidermis H H pa {rom serious infections for which
E H oxacilin MICS are 05-2 pglmL.
seuaintermedius H : po may be tested for meca or for
5 soneto H H fl PBPZa, Isolates that test meca or

PBPZa negative should be
h : reported as methicilin (oxacilin)
susceptible.
H H po ‘See general comments (5) and(8)
H ‘and comments (8) (11), and (12

‘GEPHEMS (PARENTERAL)

E | CaRaroine | S aveus, ET] F5 2 = ST = 7 28 | (18) The broakpaintorsuscapibie
indluding MRSA 2 is based on a dosage regimen of

600 mg administered every 12h

(19) The breakpoint for SDD is
based on a dosage of 600 mg every
Bh administered over?

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Fi Table 2C. Staphylococcus spp. (Continued) El
g inierpreive Categories and | interpretive Categories and pl
E Zone Diameter Breakpoints, MIC Breakpaints, €
Staphylococcus
o [FestiReport Antimicroblal spp. Disk Dearest whole mm mom, El
a: Group | "Agent indestions (content | s Ts: 1 {Re | s Iso! ı IR Comments E
B “GLYCOPEPTIDES E
4 (20) MIC tests shou be performed i determine the suscoptidity of o soates of staphylococci to vancomycin. The disk test does not dférrtate vancomycin susceptible 8
islotes of aurus from vaneomyen intermediate slates, nor does he test diferente emong vancomycinsusceptbl, termediate, and resistant isolates of Staphylococcus 8
spp thr than $ aureus al ofvch gue smlgrsze zones tino El
E © | Vancamyan |S auress AS | AMS aus vancomycin. El
Susceptible solates may become >
E Yancomyenimemediate dung the
course of prolonged therapy
a (22) Send any S aureus riche
ES Yancomyen 1 28 gmk toa real
E laboratory Ses Appendi A
5 Aso roer to Table 3 fr. aureus
= Stochapter3 12 m M07? eng
& Sibchaptr 39 102
& E | = | = : =: 6 532 | See comment (18)
= spp. oherthon $.
E aureus a À 2 i (23) Send any Staohyocoocus spp
Fi Oiherinan 5. aureus foi the
E ancomyen tics 252 agi 10a
E Tetra laboratory Ses Appendix A
See aso Subchapter 12 in MOT? and
Subchapter 3.9 MO2!
UiPOGLYCOPEPTIOES:
‘C[Dabavenan TS aureus SE = IECEBRESEEESE aE
© [ Ontavenen —| incuang esa [= o
© —frroivonen AAA o AR
MT Tercoolonn —] Asp [= [=P eg ig
TiPOPEPTIDES
| Oaplomyan TAlstapnyooea | = I = F = 7 = Pe | 81 # = f=F = [A)Degiomensnoulanatberepored
4 Jr cates Fam the espratoy tract
AMINOGLYCOSIDES
(25) Forsiaphycoco that test susceptible, gentamicin is used oy in combingion wth other acta agents that test susceptible
S| Gentamen | Alsaphyocecc | tou | #15: =: teta ct? | ea! — 1 8 tere]
E
B IE
: E

Table 2c

Staphylococcus spp.
‘02 and MO7

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Fi Table 2C. Staphylococcus spp. (Continued) El
g Irkerpreiwe Categories and | —Tnkerpreive Categories and El
E Fuß Tieiceccun Zone Diameter Breskpoits, ic Breakpotnt,
a Report | Antimierobiet | pp. Disk “nearest whole mm git 3
3 a | Meere dite. lien Ce Hass 1 Mom | = emo: 1 UE —, E
UNCOSKMIDES E
A |Cindamyan [Asp | Aug Jens 11207 SM | 208] 12 24 | (0) Forleaats atest E
trythromycin resistant and ES
Samar sosoaptbts o
8: A |8
¿fusion using ine Dzone tet or by
8: EA
: before reporting cindemycin see
: ‘able an Subchaptur 391m MES and
: Stbchaptor 12m?)
=
È See camman 20)
5 FOLATE PATHWAY ANTAGONISTS
5 A | Tomaten. | Alsapmococo | 1292070210 = LT SO SE] II AS
= sulomethozole if mE pop
= [Sirenas [Arama | 20 0 | STL A] | amo
E Fa ! fopresent any aline carer avais
= i Sufonomise reparaans
E CA A LES ET [sei OCN pee E
3 PHENICOLS
i A E E get = 1 18 #22 | See commar(25)
ANSE
| Riemn PSP | Sun Lane Lee at Le I 2 Le QV Re Romp sould at bo wed
oe E: los for orimrobil bere
STRESS
5 | Gunnin | S aureus Wig [HOT = TWEET aS] er: =} E
daloprstn Er i facil asco 3 aveu
5
: IS
: Ea

Table 2c

Staphylococcus spp.
‘02 and MO7

99

Pautasas BU LIV PU PHPUIS COROT PMO PUIS

Table 2C

Staphylococcus spp.
102 and Mo7

Table 2C. Staphylococcus spp. (Continued)

D and] id Cara

En ee. ter Breakin, Wie Breakponts,

Report nae isk “nearest whole mm me

Group indewions | content | 8 so? 1 ¡elos iso} ı | R comments

OH

5 O Tat: = 3 = 3 E20 [#6 5 = 3 | RIE
Gion ones shoud samned
¿sg ansia Orgenams th
rentrt resus by ask fusion
‘ould be contmad using an MIC
meinst

[Tess San EE EE EE EEE EE

indus MRSA i

‘Abbreviations: ATCC®, American Type Culture Collection; BMHA, blood Mueller-Hinton agar; CAMHB, cation-adusted Mueller Hinton broth; |, intermediate
ICR, inducible clindamycin resistance; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; MRS, methicilin (oxacillin)-resistant staphylococci;
MRSA methiclin (oxaclllin)esistant S. aureus: PBP2a, penicilin-binding protein 2a; PCR, polymerase chain reaction; OC, quality control; R, resistant;
S, susceptible; SDD, susceptible-dose dependent; UTI, urinary tract infection.

Footnote
a. ATCC is a registered trademark of the American Type Culture Collection
References for Table 2C

Y CLSI. Performance Standards for Antimicrobial Disk Susceptibilty Tests. 13th ed. CLSI standard M02. Wayne, PA: Clinical and Laboratory Standards
Institute; 2018.

2 CLSI. #D2 Disk Difusion Reading Guide. 1st ed. CLSI quick guide MOZQG. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

3 CLSI. Methods for Dilution Antimicrobial Susceptibiliy Tests for Bacteria That Grow Aerobically. 11th ed. CLSI standard MO7. Wayne, PA: Clinical and
Laboratory Standards Insitute; 2018.

+ Garcia-Álvarez L, Holden MT, Lindsay H, et al. Methicilin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in
the UK and Denmark: a descriptive study. Lancet Infect Dis. 2011;11(8):595-603.

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67

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Table 20

Enterococcus spp.
‘oz and MOT

Table 2D. Zone Diameter and MIC Breakpoints for Enterococcus spp.

Testing Conditions Routine QC Recommendations (see Tables 4A+1 and 5A-1 for acceptable
OC ranges)
Medium: Disk fusion: MHA
Broth dluion: CAMHB; CAMHB supplemented to | | Disk diffusion
50 pg/mL calcium for daptomycin $. aureus ATCO® 25923
‘Agar dluion: MHA; agar dition has not been validated
for daptonrycin Dilution methods:
Inoculum: Both culture method or colony suspension, equivalent to | | E faecalis ATCC® 29212
2 05 MeFarland standard
Incubation: _35°C:22°C; ambient air Refer to Tables 44-2 and 5A-2 to select strains for routine QC of
Disk difusion: 16-18 hours Hactam combination agents.
Diution methods: 16-20 hours
All methods: 24 hours for vancomycin When a commercial test system is used for susceptibility testing, refer to the

‘manufacturer's instructions for QC test recommendations and QC ranges.

Refer to Tables 3F and 31 for additional testing recommendations, reporting suggestions, and QC.
General Comments

(1) For isk difusion test a maximum of 12 disks on a 150-mm plate and no more than 6 disks on a 100-mm plate; disks should be placed no less than 24 mm
apart, center to center (see MO2,' Subchapter 3.6). Each zone diameter should be clearly measurable; overlapping zones prevent accurate measurement.
Measure the diameter of the zones of complete inhibition (as judged by the unaided eye), including the diameter ofthe disk (see the 192 Disk Difusion
Reading Guide). Hold the Pet plate a few inches above a black background iluminated with reflected light, except for vancomycin, which should be read
‘with transmitted ight (plate held up to light source). The zone margin should be considered the area showing no obvious, visible growth that can be detected
with the unsided eye. Ignore faint growth of tiny colonies that can be detected ony with a magnifying lens atthe edge ofthe zone of inhibited growth. Any
discernible growth within the zone of inhibition indicates vancomycin resistance.

(2) For enterococci when testing chloramphenicol, erythromycin, linezolid, tedizolid, and tetracycline by broth microdilution MIC, trailing growth can make end
point determination dificult. In such cases, read the MIC atthe lowest concentration where the tailing begins Tiny button of grouth should be ignored (see
MO7, Figures 3 and 4)

(3) WARNING: For Enterococcus spp. a
sulfamethoxazole may appear active in vto, but they

ycosides (except for high-level resistance testing), cephalosporins, clindamycin, and trimethoprim:
not effective clinically, and isolates should not be reported as susceptible.

(4) Synergy between ampicilin, penicilin, or vancomycin and an aminoglycoside can be predicted for enterococci by using a high-level aminoglycoside
(gentamicin and streptomycin) test (see Table 34).

(6) Intermediate ranges denoted with a “*” for the applicable antimicrobial agents in the drug groups in Tables 2 are based on the known ability of
these agents to concentrate in the urine; some agents may also have the potential to concentrate at other anatomical sites (eg, epithelial lining).

NOTE: Information in boldface type is new or modified since the previous edition.

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Table 2D. rococcus spp. (Continued)
inferpative Cafegoron and
Zone Diameter Interpretive Categories and
Sreakpont, Wie Breakpetnts,
Tesumepont | Antimicrobial | Disk nearest ole mm gin
Group gent content | si 1 | R | s sw ı IR comments
PENCIL
A [Penn Toms [ SS ı E (Ouen scopy ts sue
A | Amen mi | ET ED ©? 816 | bouseatopronuttne sci otemonctin Ampli
rats maybe vedo precia suscepti
mochis caerse, amic subactm. and
piperaclintazobactam among non-Bactamase-
brodueng erterococt. Ampeln Susoopiy canbe
tsedto prea mpenom suscepubity proving ne
Specie s conte tobe E focal

TONPUE TON mn son DE

(7) Enterococci susceptible to peniclin are predictably
susceptible fo ampli, amoxialin, ampicuin-
sulbactam, emoxciin-ciavulanate, and piperaciln-
tazobactam for non-P-actamase-producing,
enterococ However, enterococci susceptible to
ampıclin cannot be assumed to be suscaptibl to
penieil. peniil results are needed, tasting of
penis required,

(8) Rx Combination therapy wäh ampicilin, penicitin,
or vancomycin (for susceptible stains only) plus an
‘aminoglycoside, is usualy indicated for senous
enterococeal infections, such as endocards, unless
high eve resistance to bath gentamicin and
streptomycin is documented: such combinations are
predicted to resultin synergistic Kling of the
Enterccoccus For strains wit low-level penicilin or
ampli resistance when combination therapy with a
P-lactam is being considered, also see addtional
{esting and reporting information in Table 30°

‘pauiasar SNA [IV ANS Papas Kuom1ogoz PLO [IHL

(9) Ponictin or ampictin resistance among
fenterococa due to Pactamase production has been
reported very rarely. Penalin or ampiclin resistance
ue to Plactamase production is not retably detected
wih routine disk or dition methods buts detected
Using a drectnireceín-based lactamase tet
Because ofthe any of Plactamase-postve
enterococa, this est does not need to be performed
Tourney but can be usadin selected cases. A postive
lactamase tes predets resistance to pencilin as
allas amino- and ureidopenciin (see Glossary )

Po HE DOUX

69

Table 20

Enterococcus spp.
‘M02 and MO7

Table 20

Enterococcus spp.
‘Moz and MO7

a: Table 2D. Enterococcus spp. (Continued) =
Tntarprtive Categories 3
and |=
B Zone Diameter Interpretive Categories and 3
; Bee, we Satpal E
: Testmeport | Antimieroblal | pick | nesrestwhele mm vain pl
À Group Agent | content [si ı i R| s io: 1 IR comments
: ‘GLYCOPEPTIDES
4 © | Vancanyen Mus pe: Wr; en] <a =; 5-18 5 232 | (Ho) hon testing vancomyen agains enterocoen,
plates shouldbe hla ful 24 haus for accurate
{etecionofresistance, Zones shouldbe examined
{sig termes ight, the presence ofa haze or
à any rom vt the Zone of nisbiton ndostes
À cosita. Orgasms win intermediate zones
E Shou be tested by an MIC method as deserbedin
: HOT For isolates br unich the vencomyan ics
: ar 8-16 gL. pertrm biochemical tests or
à ¡Sertcaton a ted under a Vancom in MIC
: ES gim test found in Table 30
Seo general comment (4) and comment
A LPOGLYCOPEPTIDES.
8 © | Dabavanan E CES - =] {1} For rporing against vancomyon-suscopile
g: i i E feccala
$: 7 Toa Se IE ps comment]
E ©] Telavanan Ste = Dose = = [See comment)
A Im: | Teroplanın Da [su mem IE ==
2: LIPOPEPTIDES
: © | Damon EEES = = 38 112) Daptemyon should nat be reporta Tor seat
: E faecium only from ho respeatory act
3 (13) The breakpoint for SDD is dona
3 {Tovage regimen of 8-12 mag administered
E every 24h and ls intended or serious infections
ue lo E fasclum. Consultation with an
infectious diseases specialists recommended
3 5 | Daptomyein O E = 3 (14) The breakpoint for susceptible Ts based on
ES Enterococcus à dosage regimen 018 mg/kg administered
È app. other than every Zn.
E E faecium 3
È i See comment (12) <
E WACROUDE: E
5 © | emmoman Mono |; wT ei | os 1 =} 14} 28 | (B)Notrutnely roparted on olaes tome 2
= E 4 : H Sinan tat É
€ 2
5 ©
E E
2 z
£ El

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g: Table 2D. Enterococcus spp. (Continued) 3
8: Interpretive Categories and | nterpreive Categories and WIC El
E Zone Diameter Breakpoints, Breakpoint 5
Re TesuReport | Antimicrobial | Disk ares whe et Him _—_ 3
a: Group Agent | content |S 1 R | s isi ı IR Comments El
: TETRAGYCUINES 3
2 16) Organisms tat are susceptible teracyaine are also considered susceptible to doxycycine and minocycine. However, some organisms tht are Intermediate or resistant to E
tetracycline may be susceptible to doxyeycino, minocycline, or bath E
El U Tetmojeino Du | 219 11518] su | <a | - 73320 E
Ss: ‘Oo Doyeyeine ug (em 1-15 Tem [ea M 8
Bi © _ ]Mroggine ug [219 Wen sin | sa; - ; 0; 316
8: FLUOROQUINOLONES
à U | Cortossem Sn | Em wea] sm | <1; 2 + à
Y |tstotoradn suo | 211 ¡tn si | 2 ; dj 28
ha 0 | Gaston Sug ELA tet ste REN a" te
8: | Woioxacin DA | LE LOUE
ES i d lates only.
2: TNITROFURANTOWNS.
E: U [Nirofurnion [sou [3171 1516: sm [cm - 1 : 1x |
= ANSANVENS.
È ° |Riaman E77 Pie fate] <1] ~ {2} 2% | (la) Re Rifampin should not be used alone for
5 H i ii H antimicrobial therapy
E FOSFOYEINS
8: UD] Fostomyon ong | 210 1987 512 | «68 : = ; 128 ; 2268 | (18) Fortestng andveporing af E Feecalsumary
Waa sales ony,
ES
: (20) The approvedMIC testing methods agar
: Siuton, Agar meda should be supplemented wih 25
: g/mL of lucose-6 prosphate Bro dision testing
Should not be performed,
: (21) The 2009 fostomyein disk contains 509
A Qucose-& phosphate
: PHENCOLS
À © Toman] sou | sw 17} em | <6 | — | 16 | >32 [oecmmentts
‘STREPTOGRANING
: © | Cunuprsim Er SB] st | = 1 2} 24 | @2}Forreporing agonst vancomyanresisant
: alos : Entrocaceus fascism
: ‘CXAZOUIOIN
ET TO [2 72.
E Teazoid = eos: = (23) Forreporing agent E Taca
2 bbrewaons: ATOC® American Type Culo Coleaion; CAMAS, caen adustad Muse Hinton bra Load: MFA. Maalr-Hinton agar MIC, minimal z
inhibitory concentration; QC, quality contrl;R, resistant; S, susceptible; SDD, susceptble-dose dependent 3
: E

Table 20

Enterococcus spp.
‘M02 and MO7

Pautasas SHV PU PHPUIS COROT PU PUIS

Table 20

Enterococcus spp.
‘Moe and MO

Table 2D. Enterococcus spp. (Continued)

Footnote

ATCC®is a registered trademark of the American Type Culture Collection

References for Table 2D

CLSI. Performance Standards for Antimicrobial Disk Susceptibilty Tests. 13th ed. CLSI standard MO2. Wayne, PA: Clinical and Laboratory Standards
Institute; 2018.

CLSI. M02 Disk Diffusion Reading Guide. 1st ed. CLSI quick guide MO2QG. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

CLSI. Methods for Diltion Antimicrobial Susceptibilty Tests for Bacteria That Grow Aerobicall. 11th ed. CLSI standard MO7. Wayne, PA: CI
Laboratory Standards Insitute; 2018.

Murray BE, Arias CA, Nannini EC. Glycopeptides (vancomycin and teicoplanin), streptogramins (quinupristin-dalfopristin), Iipopeplides (daptomycin), and
lipoglycopeptides (telavancin). In: Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 8th ed.
Philadelphia, PA: Elsevier Saunders; 2015:377-400.

land

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73

Table 2€

Haemophilus nfuenzoe and Haemophilus parainfuenzae
+ Mo2 and, Mor

Table 2E. Zone Diameter and MIC Breakpoints for Haemophilus influenzae and Haemophilus parainfluenzae ES
8
Testing Conditions Routine QC Recommendations (see Tables 44-1, 48, 54-1, and 5B for ig
acceptable QC ranges) E
Medium: Disk difusion: HTM 2
Broth dlution: HTM broth Hi influenzae ATCO® 49247
H influenzae ATCC? 49768
Inoculum: — Colony suspension, equivalent to a 0.5 MeFarland standard
prepared using colonies from an overnight (preferably 20-to | | Use either H influenzae ATCC® 48247 or H. influenzae ATCO® 49766 or both
24 hour) chocolate agar plate (see comment (2) ofthese strains, based on the antimicrobial agents to be tested. Neither strain
has QC ranges for all agents that might be tested against H. influenzae or
: Incubation: 36'C22'C H parainfluenzao.
: Disk difusion: 5% CO: 16-18 hours
: Broth dilution: ambient air; 20-24 hours E coli ATOC 36218 (when testing amoxicilin-clavulanate)
à When a commercial test system is used for susceptibility testing, refer to the
2 manufacturers instructions for QC test recommendations and QC ranges.
a: General Comments
E: (1) Haemophilus spp. as used in this table, includes only H. influenzae and H. parainflienzae. See CLSI document MAS! for testing and reporting
E: recommendations for other species of Haemophilus.
À 1 (2) The 05 MeFarland suspension contains approximately 1 to 4 10* CFUImL. Use care in preparing this suspension, because higher inoculum concentrations
E : may lead to false-resistant results with some f-lactam antimicrobial agents, particularly when p-lactamase-producing strains of H influenzae are tested.
á (8) For disk difusion, test a maximum of 9 disks on a 150-mm plate and 4 disks on a 100-mm plate. Measure the diameter ofthe zones of complete inhibition (as
§: judged by the unaided eye, including the diameter ofthe disk. Hold the Peti plate a few inches above a black background iluminated with reflected ight. The
rh Zone margin should be considered the area showing no obvious, visible growth that can be detected withthe unaided eye. Ignore faint growth of tiny colonies
g that can be detected only with a magnifying lens at the edge of the zone of inhibited growth. With trimethoprim and the sulfonamides, antagonists in the
a: medium may allow some slight growth; therefore, disregard slight growth (20% or less of the lawn of growth) and measure the more obvious margin to
Y: determine the zone diameter.
E: (4) For isolates of H influenzae from CSF, only results of testing with ampicilin, any of the 3rd-generation cephalosporins listed below, chloramphenicol, and =
3 meropenem are appropriate to repor. E
8: El
& ! (6) Amoïcilin-clavulanate, azithromycin, cefactor, cefdnir, cefxime, cefpodoxime, cefprozi, cefuroxime, and clarithromycin are used as empire therapy for 8
= respiratory tract infections due to Haemophilus spp. The results of susceptibility tests with these antimicrobial agents are often not necessary for management ES
ge: of individual patients. e
8: 5
a: E
i: 3
& El

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Fi Table 2E. Haemophilus influenzae and Haemophilus parainfluenzae (Continued) El
S El
E (6) To make HTM: Prepare a fresh hematin stock solution by dissolving 50 mg of hematin powder in 100 mL of 0.01 mol/L NaOH with heat and string unti the €
& powder is thoroughly dissolved, Add 30 mL of the hematin stock solution and 5 g of yeast extract to 1 L of MHA, and autoclave. After autoclaving and cooling, FA
= Add 3 mL of an NAD stock solution (50 mg NAD dissolved in 10 mL distiled water, fer sterlizec) aseptically. E
: NOTE: Information in boldface type is new or modifed since the previous edition. E
Tnterprtive Categories and E
Zone Diameter Breakpoints, E
2 TestíReport Antimicrobial Disk =
gl ‘Group Agent coment [si 1 À 8 Comments
E: PENICILLIN
E : À Ampeln Mio | = ; Te ei [ er; 2 EE S00 general comment)
= (1) The results of ampictin suscoptbiity ests
È should be used to pedi he act of
E amoxclin The majonty of solates ot.
5 intuenzao tha ar resistant ampilin and
= ‘moist produce à TEMAype Plactamaso
E In most cases, a drect Plactamase test can
= provide a rapid means of detecing resistence
S {o ampicin and amos
$ (8) Rare BLNAR strains ot 4 nfuenzas
E shouldbe considered resistant to amoxiiin-
aranote, ampiclin subacam,celador
celomandolo cofetamat, cafoıcd, cafe
furoxmo oracamel and pperaclin.
tazoboctam, despie apparent n vtr
Suscoptbity of some BLNAR strains to thase
agents
ELACTAN COMBINATION AGENTS
: E Ampoli-subectam a Pao SA an
E ‘Amoxcii-ciavulanaie | 201019 [20 io <19 | su? = 1 26/4 | Soe general comment ()and comment té
© Pperaclin-szobactem | —00n0ug Tre zi IT 22% —[ See comment 8)
‘CEPHENS (PARENTERAL, (including cephalosporins iii andiV. Please refer to Glossary)
8 Sous EEES ON ET
À E gous | 2 ii 5
8 Getnasone sou | 22% à - i - gi -
E Cefuroxime yo | ED Sie | sa 8; 318 | Sao genoa comment (and comment (6
© Coharaine am ES 205 f=) = [Form muerzæony u
: H H (10) Erakgoins are based on a dosaga 3
: regmen of 600 mg adminstared every 12h E
: 7 Carona ug I sm 5 Ses comment) E

Table 26

Haemophilus influenzae and Haemophilus parainfluenzae
MO2 and MO7

Table 2€

Haemophilus influenzae and Haemophilus parainfuenzae
+ Mo2 and, Mor

al Table 2E. Haemophilus influenzae and Haemophilus parainfluenzae (Continued) =
Interpreive Categories and | Interprlive Categories and E
: Zone Diameter Breakpoints, ic Broakpoints, 3
À TestRepot | Antimicrobial Disk sont E
à Group. Agent Content A ı TR Comments A
2 CEPHEMS (PARENTERAL) (Including ce losporins 1, i ssary |.) (Continued) La
: © | Cefamandole = ca 8 1316] See comment)
A ‘| estes Er a =
2 o Ceftizoxime ENT s2 a = ‘See general comment (4).
‘CEPHENS [ORAL]
e [oser E 16 | <8 1 16 O
à c [ce soup | se its i sw | se i ip to
: | Cota or SV ant - I - sit} = | See general comment)
A € Come or si E sili -
: © ‘efpodoxme sou Bi = i = 2 ich.
: [cation wig jam | eta aan
: D [erecorbet us S10 ¡me eis | ss ¡18 [232 | See nera commen (5) and comment 8)
4 ‘OT cette 3019 [ent = a
iz — | Cafetamet TI EIA es 8: 510 | Seo commen
: HONOBACTANS
a C nan Dow Les: - + - CIT
g: CARBAPENENS
E © Herapenem To 220 = = 205 == J See general comment (4
È 3 Enapenem or 1019 BB 0 >t
4 © imipenem 104 dejo | = PRESS
Ê: © | Domenen 104 ESC EI ES E CER
: MACROLIDES.
E | Citroen sj lin: sols iwi m
& TETRACYCLINES
3 (11) Organisms that re suscepti to ttraycine are aso considered susceptible o doxycycine and minocydine, However, resistance to doxyeycine and minocycine cannot be
E intra fom teme eno resistance
© __] Tetrecycine Ls [m me; m] + +: =]
E FLUOROQUINOLONES.
© | Cpreteraaner Sea P= = te —
E Tevotoracin or sa fav = Ge 2 2] -
3 5 I e | ii] Si: M
= D Gemitoran Sug [se m E
5 ‘OT atacan TI [mt = t= t= E
E ‘OT Grepatoxaan ESTI oe TS 2
> ‘OT tametoxacin Mo IES Th 2 == 2
€ ‘OT ofoxacin 599 pai ES a+ 2
E Rs CS EE IC ER B
E E
3 &
E E

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oc Table 2E. Haemophilus influenzae and Haemophilus parainfluenzae (Continued) El
gt Interpretive Categories and. | Interpretive Categories and WIC El
8: Zone Diameter Breskpoints, Breakpeints, E
Ss: Tesieport | Antimirobia Disk nearest whole mm a E
2: ‘croup ‘Agent cot [3 | 1: a | s 1 R Comments E
: FIUUOROOUNOLONES (Continued) A
© | Trovatosen Tous ts cu E
1m | Fieroxsen Em TE = El
N FOLATE PATHWAY ANTAGONSTS E
8: na: A | 210 IR! em [as T means 8
ne Alfamelnarazoie i |
gl PRENIGOLS
$ q ES wm | EE Bla. See general camera
(12) ot routes reported onislaes tom
= the urinary trac.
ei ANSANVENS
EE CE O So [en mia | a: 7 TEN be apprOpnIe any erpraph an
ofcase contacts These breakpors do nt
& app herpy pateras wa invasive
= i i 1 influenzae disease.
& ‘Abbreviations: ATCC®, American Type Culture Collection; BLNAR, f-lactamase negative, ampicilin-resistant, CFU, colony-forming unit(s); CSF, cerebrospinal
5 Aid; HTM, Haemophilus test medium, |, intermediate; MHA, MuellerHinton agar; MIC, minimal invitar, concentration; NAD, f-nicainamide adenine
3 dinucleotide; OC, quality contol R, resistant; S, susceptible,
3
2 Footnote
a. ATCC® is a registered trademark of the American Type Culture Collection.
Reference for Table 2E
1 CLSI. Methods for Antimicrobial Dilution and Disk Susceptibilty Testing of infrequently Isolated or Fastidious Bacteria. 3rd ed. CLSI guideline M45.
Wayne, PA Clinical and Laboratory Standards Insitute; 2016
: E
i 3
: Ea

Table 2

Haemophilus influenzae and Haemophilus parainfluenzae
MO2 and MO7

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Table 2F

Neisseria gonorrhoeae
02 ana MO7

Table 2F. Zone Diameter and MIC Breakpoints for Neisseria gonorrhoeae

Testing Conditions Routine QC Recommendations (see Tables 48 and
SC for acceptable QC ranges)
Medium: Disk diffusion: GC agar base and 1% defined growth supplement. (The use of a
cysteine-free growth supplement is not required for disk difusion testing.) IN. gonorrhoeae ATCO™ 49226

‘Agar dition: GC agar base and 1% defined growth supplement. (The use of a
eysteine-free growth supplement is required for agar dilution tests with | | When a commercial test system is used for
carbapenems and clavulanate. Cysteine-containing defined growth supplement | | susceptbiliy testing, refer to the manufacturers
does not significantly alter dilution test results with other drugs ) instructions for QC test recommendations and QC
Inoculum: Colony suspension, equivalent to a 0.5 McFarland standard prepared in MHB or ranges.
(0.9% phosphate-buffered saline, pH 7, using colonies from an overnight (20- to
24-hour) chocolate agar plate incubated in 5% CO:
Incubation: 36°C+1°C (do not exceed 37°C); 5% CO»; all methods, 20-24 hours

General Comments

(1) For disk diffusion, test a maximum of 9 disks on a 150-mm plate and 4 disks on a 100-mm plate. For some agents, eg, fluoroquinolones or cephalosporins,
only 2 to 3 disks may be tested per plate. Measure the diameter of the zones of complete inhibition (as judged by the unaided eye), including the diameter of
the disk. Hold the Petri plate a few inches above a black background iluminated with reflected light. The zone margin should be considered the area showing
no obvious, visible growth that can be detected with the unaided eye. Ignore faint growth of tiny colonies that can be detected only with a magnifir
the edge of the zone of inhibited growth.

(2) The clinical effectiveness of cefotetan, cefoxitin, and spectinomycin for treating infections due to organisms that produce intermediate results with these
agents is unknown,

(3) For disk difusion testing of N. gonorrhoeae, an intermediate result for an antimicrobial agent indicates either a technical problem that should be resolved by
repeat testing or a lack of clinical experience in treating infections due to organisms with these zones. Strains with intermediate zones to agents other than
cefotetan, cefoxitin, and spectinomycin have a documented lower clinical cure rate (85% to 95%) compared with > 95% for susceptible strains.

(4) The recommended medium for testing N. gonomhoeae consists of GC agar to which a 1% defined growth supplement (1.1 g L-cystine, 0.03 g guanine HCL,
0.003 g thiamine HCI, 0.013 g para-aminobenzoic acid, 0.01 g B12, 0.1 g cocarboxylase, 0.25 g NAD, 1 g adenine, 10 g L-gutamine, 100 g glucose, 0.02 g
ferric nitrate, 25.9 g L-cysteine HC! [in 1 L H2O) is added after autoclaving.

NOTE: Information in boldface type is new or modified since the previous edition.

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Fi Table 2F. Neisseria gonorrhoeae (Continued) El
£ interpretive Categories and a
E Zone Diameter Interprative Categories and €
E Breakpoints, IG Breakpeints, 2
g: TestiReport Antimicrobi Disk are wola mee, Bin E
: Group Agent come [si 1 ir | si 1 TOR Comments E
2 PENCILUNS. E
© [rem Wome | a7 20 Te | O y
3 (6) A postive Blactamasetst reds El
restant penclin, ampeil and 7
El no
El (6) A piectamaso test detects on formo!
Ponclin resistance in Y gonormoe and aso
ES May be used provide epidemiological
& information. Strains with chromosomally
3 mediated resistance can be deleted oy by tna
5 sk sion method othe agar ton MIC
E metros.
& (7) Gonococei that produce zones of inhibition of
E 19 mm around a 10-unt peniclin disk ar Way
5 io be placamase-producing Srs, However,
El the Plactamas test remains preferable to ther
El suscepbbity methods Fr rapid, accurate
E racognton of ths plasmid-mediated pelin
B resistance
‘CEPHENS (PARENTERAL) (ncludiag ce Tiana V. Please refarto Glossary)
À [commons 28; - 5 - [O8 - po
CR cetoxtn ERE EC | a E ETA
© [Cetepms A os
0 [Cebtaums a 0
© Cobiatan aaa ia aaa
© [somme ze 3 ES ES
GEPHENSTORAL)
À | Cemme EE = EE HET EE ES
Cabo 3a} = fo = =
E
B
al a

Table 2F

Neisseria gonorrhoeae
"oz and MO7

Table 2F

Neisseria gonorrhoeae
02 and Mor

2: Table 2F. Neisseria gonorrhoeae (Continued) E
q Interpretive Categories 3
: and =
a Zone Diameter Interpretive Categorie 3
: MIC Breakpoints, E
: TestReport ‘Antimicrobial Disk vai pl
e “Group Agent comet [si i ie | s T 1 Tor Comments
WACROLIDES.
À [rem E A de | = =] Bh Ths breaiporn presumes that azthromyan
i (1 single dose) usadın an approved
H ragmen Hat includes an adátional
i medal agen le, catiaxone 250 mg IM
H Singe oose)
q TETRACYCLNES
a (©) Organisms that ao susceptible to tetracycino are als considered suscaptbl o doxyeycine and minocyeine,
à À Telacyeine ug | 298 : S37; 500 | 202 : 081; 22 | @O)Gonocooa winJOyg taaan dak
2 ne diameters 01.219 mm usualy indicate à
à Blasmicmedatod tetracycline resistant
À M goneroaae slate Resistance n these
Stans shouldbe confemed by a sien est
{MIC 2 15 gt}
a: FLUGROGUINOLONES
8: Seo general comment (3)
8: A] Coriocen Tsu Lost 240 Fey | sooo TomosT si
a: AMINOCYGLTOLS
a: 0 Speo Tong ENE RECIO E
3 Abbrevalions: ATC®, American Type Culture Collection, 1, intermediate; IM, intramuscular, MHB, MusllerHinton broth, MIC, minimal inibiery concentration;
È 2 NAD, fenicotinamide adenine dinucleotide; pH, negative logarithm of hycrogen ion concentration; OC, quality control; R, resistant, S, susceptible.
3 Footnote
E: a. ATOC® is a registered trademark of the American Type Culture Collection.
3 M
5: E
a
&: 3
a: 2
8: 8
q: E
2: E
A El

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81

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Table 2G. Zone Diameter and MIC Breakpoints for Streptococcus pneumoniae

Table 2G

Streptococcus pneumoniae
‘Moz and MO7

Medium:

Testing Conditions

Disk diffusion: MHA with 5% sheep blood or MH-F agar (MHA with 5% defibrinated
horse blood and 20 ygimL NAD)

Broth dilution: CAMHB with LHB (25% to 5% viv) (see MO7! for instructions for
preparation of LHB)

‘Agar dilution: MHA with sheep blood (5% VA); recent studies using the agar dilution
method have not been performed and reviewed by the subcommittee,

Inoculum: Colony suspension, equivalent to a 0.5 McFarland standard, prepared using colonies | | MHA,
from an overnight (18- to 20-hour) sheep blood agar plat
Incubation: 35°C22°C When a commercial test system is used for

Disk diffusion: 5% CO»; 20-24 hours
Dilution methods: ambient air; 20-24 hours (CO, if necessary, for growth with agar
dilution)

Routine QC Recommendations (see Tables 48 and
SB for acceptable QC ranges)

$. pneumoniae ATCC® 49619

Disk effusion: deterioration of oxacilin disk content is
best assessed with S. aureus ATCC? 25923, with an
acceptable range of 18-24 mm on unsupplemented

susceptibilty testing, refer to the manufacturer's
instructions for QC test recommendations and QC
ranges.

General Comments

(1) For disk diffusion, test a maximum of 9 disks on a 150-mm plate and 4 disks on a 100-mm plate, Measure the diameter of the zones of complete inhibition (as
judged by the unaided eye), including the diameter of the disk (see the MO2 Disk Diffusion Reading Guide’). The zone margin should be considered the
area showing no obvious, visible growth that can be detected with the unaided eye, Do not measure the zone of inhibition of hemolysis. Measure the zones
from the upper surface of the agar illuminated with reflected light, with the cover removed. Ignore faint growth of tiny colonies that can be detected only with a
‘magnifying lens at the edge ofthe zone of inhibited growth. With trimethoprim and the sulfonamides, antagonists in the medium may allow some slight growth;
therefore, distegard slight growth (20% or less ofthe lawn of growth) and measure the more obvious margin to determine Ihe zone diameter.

(2) For pneumococci when testing chloramphenicol, cindamycin, erythromycin, linezolid, tecizolid, and tetracycline by broth microdilution MIC, traling growth can
make end-point determination diffcult. In such cases, read the MIC at the lowest concentration where the trailing begins, Tiny buttons of growth should be
ignored (see MO7,' Figures 3 and 4). With trimethoprim and the sulfonamides, antagonists in the medium may allow some slight growth; therefore, read the
end point at the concentration in which there is = 80% reduction in growth compared with the control (see MO7, Figure 5).

(3) Amoxicilin, ampicilin, cefepime, cefotaxime, cefriaxone, cefuroxime, ertapenem, imipenem, and meropenem may be used to treat pneumococcal infections;
however, reliable disk diffusion susceptibility tests with these agents do not yet exist. Their in viro activity is best determined using an MIC method,

(4) For S. pneumoniae isolated from CSF, penicilin and cefotaxime, ceftriaxone, or meropenem should be tested by a reliable MIC method (such as that
described in MO7') and reported routinely. Such isolates can also be tested against vancomycin using the MIC or disk diffusion method,

(6) For disk diffusion, results using MHA with 5% sheep blood and MH-F agar were equivalent when disk contents, testing conditions, and zone
diameter breakpoints in Table 2G were used. Disk diffusion QC ranges for S. pneumoniae ATCC® 49619 in Table 4B apply to testing using either
MHA with 5% sheep blood or MH-F agar.

NOTE: Information in boldface type is new or modified since the previous edition.

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Table 2G. Streptococcus pneumoniae (Continued)
Interpretive Categories and | Interpreive Catagories and
Zone Diameter Breakpoints, MIC Breakpoints,
TesüReport | Antimicrobial Disk nearest whole mm ait
Group Agent Content | 1 re LS TR Comments
PENICILLINS
(6) For normeningts iolates, a perc MIC 010.08 ug/n (or oxeclin zone 220 mm) can pre susceptibity to the following -lactms: ampilin oral or parenteral),
‘mpialn-subactam, emoxicilin,emoxicil<lavulente, elec, cefdnr, ceétoren, cefepime, cefotaxime, cefpódoxime, ceprozl,ceñaraine, cefizoxime, ceraxone,
cafuroxime, donpenem, ertapenem, impenem,loracarbe, meropenem

TONPUE TON mn son DE

‘S00 general comment (4)
A Penclin Tuporactin | 220 = = = = = TR oies of pneumococa wih oxacil zone
sizes 220 mm are susceptible (MIC <0 08
HO) to perillin, Penn and cefotaxime,
úcetaxone, or meropenem MICs should be
determined or isolates win oxaciln zone
siameters $19 mm, because zones < 19 mm
‘occur with penicilir-esistant,-ntermediate, or
‘attain susceptible trans. For isolates with
oxaclin zones<19 mm, do nat report penlin
as resistant without performing a penicilin MIC
test
7 39 | (@) Rec Doses of miravenous pen or east
2 millon uns every 4 hours in adits with
normal renal function (12 milion unis per day)
can be used to eat nonmeningeal
‘pneumococcal infections dus Lo strains wth
peniclin MICs 52 ygimL. Strains wth an
Intermediate MIC of 4 ug/ml. may necessitate
penicilin doses of 18-24 milion unts per day.

A Pan parenteral = en E
(nonmenngtis)

Pauasau SNA [IV ANS Papas LOMO PLO [IHL

(9) Forall isolates other than those from CSF.
report intrpretations for both meningits and
a A nonmeningti
A Parlin parer = = = 2008 = Borna | 110) Rx Use ofpenn m meningitis requires
(meningtis) A a therapy with maximum doses ofinravenous
peniciin eg, at least 3 milion unis every
A hours in adits with normal renal function),

: : (11) For CSF isolates, report only meningtis
A Interpretations.

E ‘See general comment (4)
A Pen (erat = E = = [S008 À 0721 À 22 | 2} interpretations for oral penal maybe
penicilin Y) H H reported fr isolates other than those rom CSF

Po Oe DOUX

ss

Table 26

Streptococcus pneumoniae
Mo2 and MO7

vs

“PAS SHBU IF “IIS SpEPUO'S CLORIOGPT PLO [PMID

Table 2G. Streptococcus pneumoniae (Continued)

Table 2G

Streptococcus pneumoniae
‘Moz and MO7

Interpretive Categories
and
Zone Diameter Interpretive Categories and
Breakpoints, MIC Breakpoints,
‘Antimicrobial Disk nearest whole mm watt,
‘Agent content | 5 iR ST 1 R Comments
PENICILUNS (Continued)
© Amon = = =~ > 7) + + ed
(rormeningtis) E
© | Amoxieinlarulanste san 42 ia
(normenngts
‘CEPHEMS (PARENTERAL) (including eephal I, I, and. Please refer to Glossary)
‘See comment (6)
° Cefepime menngts] = = ~~ = | $05 T 32 | (13) niño Unted Stats, or CSF isolates
i opor any nonmeningis imerpretaions
There isnot an FDA-approved indication for
H the use of cefepime for meningitis in the
United States

5 Catepime Tnonmeninais] = = er 7 39 | 14) the Unted States, reparer
interpretations for nonmeningts and include
{he nonmeningtis notation on te report

E Cofotaxme (meningitis) = 305 7 32 | (16) For CSF isolates, report oniy meningitis

Gettnaxone (meningitis) - <05 1 22 | interpretations
116) Rx Use of cefotaxime or cofriaxone in
‘meningitis raqures therapy with maximum
doses
See general comment (4).

E Gefataame mermanınais] = H = 7 BA] 197) For at isolates other than those fom

E Cefnexone (nonmeningiis) - at 2 24 | CSF, repo interpretations for both meningtis
‘and nonmeningts

T Cotaroina (nonmenmgis] | song | 228 $ = I = | 0 | = =] (18) Ereakpoints are Based on a dosage,
regmen of 00 mg administered every 12h

le Coturoame (parenteral) = = = as 7 El

CEPHENS (ORAL)
‘Soe comment (6)

c Cefuroxime (ora) = = ES = 7 33 | (19) interpretations for oral cefuroxime may
be reported for isolates other than those
from CSF.

Catador = = EA 7 =

© eta = AE A El

© Cepodoume. = A ET | El

o Ceprozi = = Eee 3 El

à Loracarer = AA EJ

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: Table 2G. Streptococcus pneumoniae (Continued) ES
E Interpretive Categories and El
Zone Diameter Interpretive Categories and 5
Breakpoints, Mic Breakpoins, 2
: TestReport Antimicrobial Disk nearest wh gmt E
À Group, Agent content [5 RARO Comments El
À CARBAPENENS E
Ses comment (5) E
7 D | Maropenem = =p = EE ET ET comment 71 E
x © [Enapenem = j= | = | = 1.2 da =
A © | impenem = = 1 = = | cot o%0s à À
: © | Dorperem = EE INCIERTO EN INERCIA
: GLYCOPEPTIDES
: © [vengan T So TA Trama
WAGROLIDES

(20) Suscoptbilty and resistance to azithromycin, clanthromyein, and dithromycin can be predicted by testing erstvom cin

(21) Not routinely reported for organisms isolated from the urinary tract
A

Pauasau SNA [IV ANS Papas LOMO PLO [IHL

Enfhromyen 1599 | en Tien Ten [co T 08 po
Ostrom ‘Sug [ set ei gg | sos} tt
Of Canoe Tug pen pao isis EE pea
© [onimemyen EE EE EE 2
TETRACYCLINES
À (22) Organs that ae susceptible to tiracycine are also considered suscaptbe fo dowyoycne. However, resistance to doxycycine cannot be inferred fom tacycine
reste
| Taracdne 309] 23 1 Tal] a >
: 5 | Daumine a | 328 i ig | cox | os ia
: FLUOROGUNOLONES
: © | Gemfoxocn Su | 33 ST =012 ; 0% : 208 | 295 proumonao oats suscopible o
e | tevotocecn sw | en fe ©: Le | fvencuncnaro predeiany supo to
8 | Mouton sa | e a | 3 2 32 | geminosaanengmantaraan However,
B pneumoniae suscaptbe 1 gemiaracn or
E mosloxaon cant be assumedto be
A suscepti levolorasn
: O ETT ET INE paa Ts
0 [onen so su is gna | er is Tes
À 0 [spas Sug [stat RE gos tt ts
: FOURTE PATHWAY ANTAGONISTS
A A Trimethoprim. Tay] 219 ] 1808 Fern | 50505 | 119-208 Team
: sutamemovazol 23759 H i i
E PRERICOLS
: © | Chorampnarsal Ls Den: ol ca : [soma

Po Oe DOUX

ss

Table 26

Streptococcus pneumoniae
Mo2 and MO7

98

Pautasas MBA LIV PU PHPUIS COROT PU PUIS

Table 26

Streptococcus pneumoniae
‘Moz and MO7

Table 2G. Streptococcus pneumoniae (Conti

Inerbreive Caigories and
Zone Diameter Bros,
esurepor | Antimicrobial Disk
‘sup Agen content So Comments
ANAM
oy Ramon Sun | SB LISE BE 2 ME iy Ren snobs ead aloe Br
Bu BEE! roman ere
TUNCOSAMDES,

8] cindamyen Tag] Te 35] 08 05 51] romania
sd cindamyein susceple o intermediate,
destino lo OR by disk dusion using te
Dizon testo by broth microdltion e
required before reporting inaamyein
(Seo Tone Snap SNe and
Sehnen 121m WOPy
See comment 21

STREFTOCRAUNE,

> Toma | I sm rem 2 [7 1 > rs]
DIENT

© Tina [3 [= 7 - I 2 4

==]

Abbrevalons: ATOC®, American Typs Cultura Collection: NAD, nicotinamide adenine dinucleotide, CANHB, calowadusted MudlerHinion brah;
CSF, cerebrospinal fui CR, inducible clindamycin resistance; FDA US Food and Drug Adminstration: intermediate; LH, lysed horse blood; MHA, Muelle
Hinton agar; MH-F agar, Mueller-Hinton fastidious agar; MIC, minimal inhibitory concentration; OC, quay contol, resistant, S, susceptible

Footnote
a. ATCC®is a registered trademark of the American Type Culture Collection.
References for Table 26

Y GLSL Methods for Diltion Antimicrobial Susceptibiliy Tests for Bacteria That Grow Aerobicaly. 11th ed. CLSI standard MO7. Wayne, PA: Clinical and
Laboratory Standards Institute; 2018

? ELSI. M2 Disk Diffusion Reading Guide. 1st ed. CLSI quick guide M02QG. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.

2 CLSI. Performance Standards for Antimicrobial Disk Susceptibilty Tests. 13th ed. CLSI standard MO2. Wayne, PA: Clinical and Laboratory Standards
Institute; 2018.

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87

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Table 2H-1. Zone Diameter and MIC Breakpoints for Streptococcus spp. B-Hemol

Table 2H-1

Streptococcus spp. Hemolytic Group
‘Moz and MO7

Group

Testing Conditions

Routine QC Recommendations (see Tables 4B and

5B for acceptable QC ranges)
Medium: Disk diffusion: MHA with 5% sheep blood
Broth dilution: CAMHB with LHB (2.5% to 5% vi); the CAMHB should be S. pneumoniae ATCC® 49619
‘supplemented to 50 g/l. calcium for daptomycin (see MO7! for instructions for
preparation of LHE) When a commercial test system is used for
Agar dilution: MHA with sheep blood (5% vv); recent studies using the agar dilution | | susceptibility testing, refer to the manufacturer's
method have not been performed and reviewed by the subcommittee, instructions for QC test recommendations and QC
Inoculum: — Colony suspension, equivalent to a 0.5 McFarland standard, using colonies from an | | ranges.
‘overnight (18- to 20-hour) sheep blood agar plate
Incubation: 38°C#2°C

Disk ciffusion: 5% CO»; 20-24 hours
Dilution methods: ambient air; 20-24 hours (CO
dilution)

necessary, for growth with agar

Refer to Table 3H for adeltional testing recommendations, reporting suggestions, and QC.
General Comments

(1) For disk diffusion, test a maximum of 9 disks on a 150-mm plate and 4 disks on a 100-mm plate. Measure the diameter of the zones of complete inhibition (as
judged by the unaided eye), including the diameter of the disk (see the M02 Disk Diffusion Reading Guide’). The zone margin should be considered the
area showing no obvious, visible growth that can be detected with the unaided eye. Do not measure the zone of inhibition of hemolysis. Measure the zones
from the upper surface of the agar illuminated with reflected light, with the cover removed. Ignore faint growth of tiny colonies that can be detected only with a
‘magnifying lens at the edge of the zone of inhibited growth

linezolid, tedizolid, and tetracycline by broth microdilution MIC, tailing

(2) For f-hemolyic streptococci when testing chloramphenicol, clindamycin, erythromycir
1g begins. Tiny buttons of growth

growth can make end-point determination diffcut. In such cases, read the MIC at the lowest concentration where the tra
Should be ignored (see M07, Figures 3 and 4)

(8) For this table, the B-hemolytic group includes the large colony-forming pyogenic strains of streptococci with group A (S. pyogenes), C, or G antigens and
strains with Group B (S. agalactiae) antigen. Small colony-forming f-hemoltic strains with group A, C, F, or G antigens (S. anginosus group, previously
termed ‘S. mille?) are considered part ofthe viridans group, and breakpoints for the viridans group should be used (see Table 2H-2)

(4) Penicilin and ampicilin are drugs of choice for treatment of B-hemolytic streptococcal infections. Susceptibility testing of penicilins and other f-lactams
approved by the US Food and Drug Administration for treatment of f-hemoltic streptococcal infections does not need to be performed routinely, because
nonsusceptible isolates (e, penicilin MICs > 0.12 and ampicilin MICs >0.25 jigiml) are extremely rare in any f-hemolyic streptococcus and have not been
reported for S. pyogenes. If testing is performed, any f-hemolytic streptococcal isolate found to be nonsusceptible should be re-identfied, retested, and, if
confirmed, submitted to a public health laboratory. See Appendix A for additional instructions.

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$i Table 2H. Streptococcus spp. B-Hemolytic Group (Continued) El
8: El
5: (6) Breakpoints for Streptococcus spp. f-hemolytic group are proposed based on population distributions of various species, pharmacokinetics of the €
à: antimicrobial agents, previously published literature, and the cinical experience of subcommittee members. Systematically collected clinical data were not El
8: available for review with many of the antimicrobial agents inthis table. El
a Fi
È NOTE: Information in boldface type is new or modified since the previous edition. E
E Interpreive Categories and | Interpretive Categories and 2
S: Zone Diameter Breakpoints, MIC Breakpoint 8
2: TestReport Antimicrobial Disk nearest whole mm uam.
8: Group Agent content [STR SI IR Comments
é 3 PENICILLNS
: AG) An organism that's suscepti o ponte can be considered susceptible to antimicrobial agers ted here when used for approved indications and doos nat need to be tasted
agaistinose agerts. For greuns A, BC, and © f-hemolycstreplococa,peniclin a surogata for ampialin, amoxciin, ameniclir-clvuarale, ampiiin-subactam, cetazoin,
a sfopme.cenaroine,cophradn,caphaiohin,cetaime, cefviaxone, cetizoxm, mipanem, etapenem, an mors group A -homolyc sroptoco, pert is also
E: a surogaie for cefacr. coi Ceprozi, cetbuten, cefuroxime, and cefbodovime
El A] Penciin Wins 220 3 - = = O
: N ampli som | ami | - = ee
& ‘CEBHENS (PARENTERAL) (neluding cephalosporin II, andiV Please Fear Glossary 1]
È Ses comment (5)
5 © [emma We ES NE:
El 5 cobtoxme or om | aw io E = 3
3 8 Cotrioxana song | 294 =
2 | Cetarsine aug] 20} = = = = Tr EEE aro based on a dosage regimen
A 01600 mg asminstera every 12h
‘CARBAPENEMS
‘Seo comment
© | Dorpenem = a = pan — =
© [Erapenem = à JS
© | Meropenem = ns = =
‘GLYCOPEPTIDES
© | vancomyen sous [ami | - | a Sey
TPOGLYCOPEPTIOES
© | Dalbavanon = = = = Tas: - =] @)Forreparing against 5 pyogeres
$ egalctos, and S cyagauctae
À = [Onsaren = = = EE =
À < ana = u — =
: TPOPEPTIDES
A © | Dastemyem = =} = 1 = | #1} =} = [1)Depiemyansheulinatbereponedier
i E i Isolates from tho respratary tract

Po Oe DOUX

Table 2H-1

Streptococcus spp. Hemolytic Group
'M02 and MO7

Table 2-2

Streptococcus spp. Hemolytic Group
AO and Mo7

Table 2H-1. Streptococcus spp. B-Hemolytic Group (Continued) E
Interpretive Categories and | Interpretive Categories and 3
Zone Diameter Breakpeinte, ic Breakpoints, IS
TestReport Antimicrobial Disk nearest whole mm. voit. 3
‘Group ‘Agent content [STR UE Comments E
MACRO 2
(10) Susceptalty and resistance to axthromycin, danthromyan, and dinttromyin can be predicted by testing ethromyan.
(11) Not routinely reported on isolates fom the urinary tract
A | enftremyen Mono | eat) 1620 I <i | 2028 7 08: 21 |W)Rx Recommendehens krinrapanım
A A propyl for group B sreptococa are peniiln
Or ampiclin. hough cefazolin is recommended
for peniclin-alergie women at lo nsk or
anaphıjas, those at high sk or angphlais
may receve cindamyc Group B sreploooen
re Suscopttloto ampli, peri, and
Cofazoln, but may be resistant to enthramyan
and cindamyein When a group 8 Streptococcus
isolated fom a pregnant woman wth severe
Penialin allergy (igh ik or anaphiyaxis)
Erybromycin and dindamyen (rating ICR)
B Should be tested, and ony dindamyen shoud be
5 reported Erythromycin should be tested for
ge TER determine y anodino
8: reported Soo Table 3H
8: CO arman EEE ES EE IE 71
S Of Carmona CENT ESTIMA iso ET E
2 © —T Bintromycin Hug | 216; 17; ls fT E
a TETRACYCLINES
$: {13} Orgnisms a re suscep to tatin ar lso considered suscptbl to doxyycine end mincycina, However, resistance o dowyysneandmineeyne cant be
infered fom tetracycine resistance.
8 O] Totracycine TS 1m ee ee] ii]
$ FIUOROGUNOLONES
© TLevoranaen Su Jen: 6; ajos
£ oT KT salar ta [et Te
‘OT Grepatioxacn EEE | 208) 1 2
9 [Otoısen Bug | 216 Tem in | 0 ise
= 0] Tronatoxaein Hug [ 210 Fear se I A 24
È FHENGOLS >
3 © EE Tous [sm 1 1690 1 si) [28 1 8 1 316 | Soo comment ti) E
E a
E E
5 i
€ 3
i E
3: E
A E

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8: Table 2H-1. Streptococcus spp. B-Hemolytic Group (Continued) _ Fl
gt HS Categories and El
E: "ic Breskpoints, E
ai Test Report | Antimicrobial Disk nearest whole mm vain 2
a: Srp Agent content [8 Co ER Comments E
Si TINCOSAMIDES. E
È A ‘Clindamycin 249 219 16-18 <15 3025 05 21 | See comments (11) and (12) &
E (14) Forisoates that test enftromyein E
5 Fesistant and eindamyeln susceptible or £
3: Intermediate, esting or ICR by disk difusion &
2: einge D-zone tet or by broth
Si Imieodition is required before reporting
q Sändamyein Seo Table SH, Subchapter 99 in
E SRE
= © T Gunupnstn-dotepnstin I 1sug [210 à 1618 ı si | <1 ; >; 54 ]18)RepomaganstS-pyayenss
E: OXAZOLIDINONES
5 © [umo ENT a eo tn
= O E E LE LETS LL
& d Sectes ons
El Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adusted Mueller-Hinton broth; ICR, inducible clindamycin resistance; |, intermediate;
= LHB, lysed horse blood; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; QC, quality control; R, resistant; S, susceptible
E
E Footnote
E
& a. ATCC®is a registered trademark of the American Type Culture Collection.
References for Table 24-1
1 CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically. 11th ed. CLS! standard M07. Wayne, PA: Cli
Laboratory Standards Insitute; 2018
2 LSI. M2 Disk Diffusion Reading Guide. 1st ed. CLS! quick guide M02QG. Wayne, PA: Clinical and Laboratory Standards Institute; 2018.
3 CLSI. Performance Standards for Antimicrobial Disk Susceptibilty Tests. 13th ed. CLS! standard M02. Wayne, PA: Clinical and Laboratory Standards
: E
i 3
: Ea

Table 2-2

Streptococcus spp. [Hemolytic Group
'M02 and MO7

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Table 2H-2

Streptococcus spp. Viridans Group
‘Moz and MOT

Table 2H-2. Zone Diameter and MIC Breakpoints for Streptococcus spp. Viridans Group

Testing Conditions Routine QC Recommendations (see Tables 48 and
5B for acceptable QC ranges)
Medium: Disk diffusion: MHA with 5% sheep blood
Broth dilution: CAMHB with LHB (2.6% to 5% vw); the CAMHB should be | | S. pneumoniae ATCC™ 49619
supplemented to 50 ug/ml. calcium for daptomycin (see MO7! for instructions for

preparation of LHB) When a commercial test system is used for
‘Agar dilution: MHA with sheep blood (5% vi); recent studies using the agar dilution | | susceptibility testing refer to the manufacturers
method have not been performed and reviewed by the subcommittee. instructions for QC test recommendations and QC
Inoculum: — Colony suspension, equivalent to a 0.5 McFarland standard using colonies from an | | ranges.

‘overnight (18- to 20-hour) sheep blood agar plate
Incubation: 35°C#2°C
Disk effusion: 5% COx; 20-24 hours
Dilution methods: ambient air, 20-24 hours (CO: ifnecessary for growth with agar
dilution)

General Comments

(1) For disk diffusion, measure the diameter of the zones of complete inhibition (as judged by the unaided eye), including the diameter of the disk. The zone
margin should be considered the area showing no obvious, visible growth that can be detected with the unaided eye. Do not measure the zone of inhibition of
hemolysis. Measure the zones from the upper surface of the agar iluminated with reflected light, with the cover removed. Ignore faint growth of tiny colonies
that can be detected only with a magnifying lens at the edge of the zone of inhibited growth

(2) For viridans streptococci when testing chloramphenicol, clindamycin, erythromycin, linezolid, tedizolid, and tetracycline by broth microdilution MIC, trailing
growth can make end-point determination dificult. In such cases, read the MIC at the lowest concentration where the trailing begins. Tiny buttons of growth
should be ignored (see M07, ' Figures 3 and 4).

(3) The viridans group of streptococci includes the following five groups, with several species within each group: mutans group, salivarius group, bovis group,
anginosus group (previously *S. miller? group), and mitis group. The anginosus group includes small colony-forming F-hemolyi strains with groups À C, F,
and G antigens. For detailed information on the species within the groups, please refer to recent literature.

(4) Breakpoints for Streptococcus spp. viridans group are proposed based on population distributions of various species, pharmacokinetics of the antimicrobial
agents, previously published Iterature, and the clinical experience of subcommittee members. Systematically collected clinical data were not available for
review with many ofthe antimicrobial agents in this table.

NOTE: Information in boldface type is new or modified since the previous edition.

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Fi Table 2H-2. Streptococcus spp. Viridans Group (Continued) El
S Categories and | interpretive Categories and El
E er Breakpoints, Mic Breakpoints, €
E TestReport Antimicrobial Disk nearest whole mm ya. A
8 Group ‘Agent content [SR EE IR comments E
& PENICILLIN, &
A | Penco = = = = T S012 : 0252 : 24 [{6)Vindanssreplocen wald Fom E
A | ampictin 5025 | 054 : 28 | nomalysterte anatomical sites (eg, CSF. 2
blood, Bone) shoud be est for penialin E
$: suscepti using an MIC metros E
gt (6) A peniclin MIC of 50.125 pgm isthe
: same as apenclin MIC of<012 pg/mL and
El : bot shouldbe interpreted as suscepito
: Laboratones should report an MIC af
= 0.125 gmt 95 $0 12 pi.
E (7) Rx Pericilin- or ampicilin-ntermediate
5 Isolates may necessitate combined therapy
E wth an amnogycosid fr bactencdal action
= PIACTAN CONBRATIONAGENTS
& Cefolozenetazobacem = = = =] 384 1 164 {2328 | (0) Eropont are based on a dosage
= B regimen of 15.9 adminstered every 8h.
El ‘GEPHENS [PARENTERAL] including cophalosporins LILI andiV Please referto Glossary)
E 8 Celepime u | 22 ; 23 1 at | si 7 ET
3 8 Cotolaxime sous | 22 ir i ss | os 2 24
ES 5 |cemaons gona | ba i x | Se | ii
‘CARBAPENEMS
0 Dorpanem = > a >
° Ertapenem = Sy a a ES
a ‘aropanem = a
(GLYCOREPTIDES
© | Voncamyem [wu Tem; = 7 - Tg ; — =’
TIPOGLYCOPEPTIOES
© Dalbavanen = = eS = Te: - = [SF orreporing against S anginosus group
i {nudes S angmasıs,
: i i i i S nermedus and $-consteaus on
: E Greene = Ss
À E Taiovanen = A
À TIPOPEPTIDE
o Dastonyan = - = Kae =| == | {90} Daplomyon shouldnofbe reported Tor
i i i i Isolates rom ne resprator trad
E
: |8
: E

Table 2H-2

Streptococcus spp. Viridans Group
M2 and MO7

Table 2H-2

Streptococcus spp. Viridans Group
‘Moz and MOT

Table 2H-2. Streptococcus spp. Viridans Group (Continued) =
“arrete Categories | re Categories and E
Zone Diameter Breakpoints, Mic Breakpoins, 5
Testteport | Antimierobal Di east whole nm vim E
Em Agent content RER Comments
MACROLIDES &
3. [fier and resistence oeltvonycin, dartwomyan, and arthrmyan can be predetad by esing eytromycin,
Hz rtans rotes on salts rom De unary a
Erie ‘uy Te I m Te | sos 0 7 57
nm PE EI Fr TC ES RES
D Gone TIT EE CINE Tas ERE
ones CT er CEE
2 ro
2 [FE Organo that re suscep tecno ar lso considered suscaplo to doxyajcina and mincein, However, resistance 1 doin and moine camo be
: inferred from tetracycine resistance.
© [Tetracycine [oy I 22 | 190 | si | 3 El 28 I
A e
: TOTO ED ES D EE:
À oT ota Sa Te m es
oT eaten Sug ar EE ae
D— ETT so CCC EEE
a rates PE sie tee EST IE E
$ FHENICOLS
= ET Chloramphencol T 3049 aaa 1 sw I] ca | 8 216 | Seocomment(12).
2: Homes
3 E | Cindamyon TL 2uo I 219 : 1618 3 sw | <o2s 3 05 31 | Seecomment(12)
Rs STREPTOGRAMINS
E o ] Quinupnistin-dalfopnstin T 15ug I 219 5 1618 © <15 | < 1 7 FET I
‘EAZOLIDINONES
E I EE ICI CI CE ECT
E reci CU IS as ESTE
Abbreviations: ATCC®, American Type Culture Collection: CAMHB, cation-adjusted Mueller-Finton broth; CSF, cerebrospinal uid; 1, intermediate; LHB, Iy
E horse blood; MHA, Mueller-Hinton agar; MIC, minimal inhibitory concentration; QC, quality control; R, resistant; S, susceptible.
E Footnote
= a. ATCC®is a registered trademark of the American Type Culture Collection. -
5 Reference for Table 2H-2 E
nee
aaa 1 CLSI. Methods for Dilution Antimicrobial Susceptibilty Tests for Bacteria That Grow Aerobicaly. 11th ed. CLSI standard MO7. Wayne, PA: Clinical and E
a: Laboratory Standards Institute; 2018. El
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For Use With MO2 and MO7

‘M100, 30th ed

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95

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Table 21. Zone Diameter and MIC Breakpoints for Neisseria meningitidis

Table 21

Neisseria meningitidis
‘Mo2 and MO7

Testing Conditions

Medium:

Inoculum:

Disk diffusion: MHA with 5% sheep blood
Broth microdilution: CAMHB supplemented with LHB (2.5% to
5% vl) (see MOT" for preparation of LHB)

‘Agar dlution: MHA supplemented with sheep blood (5% vi”)

Colony suspension from 20-24 hours growth from chocolate agar
°C; 5% COz; equivalent to a 0.5 McFarland
‘grown on sheep blood agar may be used for
inoculum preparation. However, the 0.5 McFarland suspension
obtained from sheep blood agar will contain approximately 50%
fewer CFUlmL. This must be considered when preparing the final
lution before panel inoculation, as guided by colony counts.

Routine QC Recommendations (See Tables 44-1, 48, 54-1, and SB for
acceptable QC ranges)

Streptococcus pneumoniae ATCCO 49618:
Disk fusion: incubate in 5% CO».

Broth microdilution: incubate in ambient air or CO: (except azithromycin
QC tests that must be incubated in ambient ar)

E coli ATCC® 26922

Disk diffusion, broth microdilution or agar dilution for ciprofoxac
nalidixic acid, minocycline, and sulfisoxazole: incubate in ambient air or

co:

1 3°C42°0; 5% CO); 20-24 hours

‘When a commercial test system is used for susceptibilty testing, refer to
the manufacturers instructions for QC test recommendations and QC
ranges.

General Comments

information on safety precautions, see Biosafety in Microbiological and Biomedical Laboratories. th ed. Washington, DC: US Department
of Health and Human Services; 2009. httpAnww cle. gov/biosafety/publications/ombiS/. Accessed 10 December 2019,

(1) Recommended precautions: Perform all AST of N. meningitis in a BSC. Manipulating N. meningtidis outside a BSC is associated with increased risk for
contracting meningococcal disease. Laboratory-acquired meningococcal disease is associated with a case fatality rate of 50%. Exposure to droplets or
aerosols of A. meningtidis is the most likely risk for laboratory-acquired infection. Rigorous protection from droplets or aerosols is mandated when
microbiological procedures (including AST) are performed on all N. meningitis isolates,

(2) Ia BSC is unavailable, manipulation of these isolates should be minimized, limited to Gram staining or serogroup identification using phenolized saline
solution, while wearing a laboratory coat and gloves and working behind a full face splash shield. Use BSL-3 practices, procedures, and containment
equipment for activities with a high pot
infectious materials. If BSL-2 or BSL-3 facilites are not available, forward isolates to a referral or public health laboratory with a minimum of BSL-2 facilites.

(8) Laboratorians who are exposed routinely to potential aerosols of N! meningitidis should consider vaccination according to the current recommendations of the
Centers for Disease Control and Prevention Advisory Committee on Immunization Practices, available at ttp/wrw.ede.govivaccines/aciprindex htm

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8: Table 21. Neisseria meningitidis (Continued) El
8: El
5: (4) For disk fusion, test a maximum of 5 isks on a 150.mm plate and 2 disks on a 100-mm plate. Measure the diameter ofthe zones of complete inhibition (as a
di judged by the unaided eye), including the diameter of the disk. Measure the zones ftom the upper surface ofthe agar iluminated with reflected light, with the El
2 cover removed. Ignore faint growth of tiny colonies that can be detected only with a magnifying lens at the edge of the zone of inhibited growth. With E
trimethoprim and the sulfonamides, antagonists in the medium may allow some slight growth; therefore, disregard slight growth (20% or less of the lawn of El
È growth) and measure the more obvious margin to determine the zone diameter. H
5 (6) Breakpoints are based on population distributions of MICs of various agents, pharmacokinetics of the agents, previously published literature, and the 3
3: experience of subcommiltee members. Systematically collected clinical data were not available to review with many of the antimicrobial agents in this table. 3
BE un Une rare mater ar aod tsa san ana te tem rat
a NOTE: formation in boldface ype is new or modfed since the previous edition
E Interpretive Categories and
E: Zone Diameter Interpretive Categories and
3: MIC Breakpeints,
5 TestReport Antimicrobial Disk vont
= ‘Group Agent Content EE —— Comments
= PENICILLIN
È © [Pen =
5 € Lame Li
El CRE
E © | Caotacme or Hu | 23%
3 € cofnacone song | 24
A ‘CARBAPENENS
©] Marepanam Dom Jai Jas: — =
MACROLIDES
© [Amen ww [ani - E = =] See genera comment)
(7) May be appropriate ony fr prophylaxis of
maningococeal case contacts, These breakpoints
do nat apply o therapy of patients with invasive
monngocodeal sense
TETRACYCUNES
© | iman [soup Tas -— > | 2 | _ + — Toma
FLUGROGUINOLONES
18) For suvellance puposes, nage acid MIC > gi ora zone $25 mm may comeste wih diminished Nuoroguanalone suscepbilty.
: € | rotor Sug | 208 T 204 | sa | som | 000 | 2012 | See comment)
5 e Lievotocen És > =i = | som i 0m i 2012
: E
: E

Table 21

Neisseria meningitidis
‘M02 and MO7

Table 21
Neisseria meningitidis

‘Mo2 and MO7

8: Table 21. Neisseria meningitidis (Continued) =
: Infrereive Categories and | Interpretive Categories and WIC 3
: Zone DlameterBreakpolns, Breakpoins, El
A TestRepor | Antimicrobial Disk nearest whole mm pa pS
3 Group Agent Content | = 1 e 5 1 R Comments Ê
4 FOLATE PATHWAY ANTAGONISTS ES
: © | Sufaorazas = = 5 | = FT 28] See commart (7.
© | Trmatnopnm: 123 | 230 | 2629 <01Y | 025475 | 20% | (6) Tnmainopnm-sufamathsazol is re
Sltamenon 227519 24 05 | prefered ds toraetecion ol sutonamige
fesistance,Trimethoprm-autamethorazole
{esting prods suscepti and resistance
to timetnopam-sufametorazole and
Sufonamides Sulfonamides maybe
à Sppropnate ony lor propias of
À imenngoraceal case coats
: PHENICOLS
3 © ‘Chloramphenicol ou | 226 ı 20-05 351 a 1 8 — | (10) Not routnely reported on isolates from
A fhe Umar toe
2 ANSAMYCI!
: © Team [Sug [asii] as 1 1 32 | Seo commana (7.
‘Abbreviations: AST, antimicrobial susceptbilly testing, ATCC®, American Type Culure Collection; ESC, biological safely cabinet: BSL-2, biosafety level 2, BSL,
t biosafety level 3; CAMHB, cation-adjusted Mueller-Hinton broth; CFU, colony-forming unit(s); |, intermediate; LHB, lysed horse blood; MHA, Mueller-Hinton agar;
g: MIC, minimal ory concentration; QC, quality control; R, resistant; S, susceptible.
8: Footnote
a: a. ATCC®is a registered trademark of the American Type Culture Collection.
È : Reference for Table 21
E: 1 CLSI. Methods for Dilution Antimicrobial Susceptibilty Tests for Bacteria That Grow Aerobically. 11th ed. CLSI standard MO7. Wayne, PA: Clinical and
a: Laboratory Standards Institute; 2018
: 7
E M
5: E
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= El
a: 2
8: 8
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99

001

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Table 2J. MIC Breakpoints for Anaerobes

Table 2)
Anaerobes

mir

Testing Conditions
Medium: — Agar dilution (for all anaerobes): Brucella agar supplemented
with hemin (5 jugim), vitamin Kı (1 ug/mL), and laked sheep
blood (5% vi)
Broth microdilution (for Bacteroides spp. and Parabacteroides
spp. only): Brucella broth supplemented with hemin (S ugmL),
vitamin Ki (1 g/mL), and LHB (5% viv)
Broth culture method or colony suspension, equivalent to
0.5 McFarland suspension
‘Agar: 10° CFU per spot
Broth: 10° CFU/mL
Incubation: 36°C 1°C, anaerobically

Broth microdilution: 46-48 hours

Agar dilution: 42-48 hours.

Inoculum:

Routine QC Recommendations (see Tables SD and SE for acceptable
QC ranges)

Test one or more of the following organisms. The choice and number of
QC strains tested should be based on obtaining on-scale end points for the
antimicrobial agent tested.

2B. fragilis ATCO™ 25286
Bacteroides theteiotaomicron ATCC? 29741

Chostrdiodes (formetiy Clostiium) die ATOCO 700057
Eggerthella lenta (formerly Eubacterium lertum) ATCC® 43055

‘When a commercial test system is used for susceptibility testing, refer to
the manufacturer's instructions for QC test recommendations and QC
ranges.

General Comments

(1) For isolates for which the antimicrobial agent MICs fall within the intermediate category, maximum dosages, along with proper ancilary therapy, should be
Used to achieve the best possible levels of drug in abscesses and/or poorly perfused tissues. If his approach is taken, organisms for which the antimicrobial

agent MICs fall within the susceptible range are generally amenable to therapy. Organisms for which the antimicrobial agent MICs are

the intermediate

range may respond, but in such cases, efficacy as measured by patient clinical response should be carefully monitored. Ancillary therapy, such as drainage

procedures and debridement, are of gre

importance for proper management of anaerobic infections.

(2) Refer to Figures 3 and 4 in CLSI document M11! for examples of reading end points.

(8) MIC values using either Brucella blood agar or Wilkins Chalgren agar (former reference medium) are considered equivalent.

(4) Broth microdilution is recommended only for testing Bacteroides spp. and Parabacteroides spp. MIC values for agar or broth microdilution are considered

‘equivalent for those species.

(8) Until additional stu
spp. and Parabacteroides spp.

NOTE: Information in boldface type is new or modified since the previous edition.

8 are performed to validate broth microdilution for testing other organisms, it should be used only for testing members of Bacteroides

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8 Table 24. Anaerobes (Continue: El
$ interpretive Categories and WIC El
E Breakpoints, €
& TestReport Antimicrobial balm El
3: proa agent zs; 1 IR aii 2
: PENILE El
4 AC | Ampsiin® 205 7 22 — [BJ Ampicii aná ponia or recommended for prmaryosing and reporing Tor ram E
AC | Pera? <05 1 22 | postve orgarsms (group A) because most tem ae Blacamase negate, but or
Sram nego orgorsm (cup C) because many ar fiotomose postive
2 (M Bacteroieo spp. re intinsicay resistant to pricilin and ampicin_Parabocterides
E pp are presumed io be restart entiln and ampic Other gam-nagaiv and
gram-postive anaerobes maybe screened for Plactomase acy win chromogenic
El Saphalospañn i Pociamase postive repr as resistant peicin, ampli, and
‘movin Be anare that Plactamoss-negatwo isolates maybe resistant Pactams by
= ‘ther mechanisms, Because higher Blood levels ae acrevable wih tae antimeroil
3 agents nfecton wth non-Blacamase-procucng organisms wi ge MIOS (24 mL)
E wth adequate dosage regimen mig be treaabl.
& {81 Results of ampicitin testing con be used to predict resus for amoxiciin
= San EE u ie
€ FLACTAN COMBINATION AGENTS
E À | Amowiclinciondonalo [cin BE
3 À | ampotnsutadan seu | 190
E A __[Ppersciintezobectem | te | 324-044
À CE {oa
‘CEPHENS (PARENTERAL) (including cephalosporin I, and To Glossary)
© [Con sf 32
© | coin seis
© Teetnoume E
© | cotnacono =” 2
©] Comtazoi =” E
©] Cotoperazone mt ®
© _ | Cotoinume =” E]
‘CARBAPENENS
A | Donpenem = ot =
A Enapenem ra CTO
A imponen E CO SO
A| Merepenem ra St 36
TETRACYGLINES
© | Teragyans = 5 T2
FLUOROGUINOLONES =
© | Moutoxsen Lei 3
| E

Table 2)

Anaerobes
Mi

zor

“pas SISI [IF “IAS SPIDPUDIS CLORIOGPT PLO PUIS

Table 2)

Anaerobes
mir

Table 2J. Anaerobes (Continued)

Interpretive Categories and
MIC Breakpoints,
TestReport ‘Antimicrobial baht
Group Agent ET: Comments
TINCOSAMIDES
À | Cindamyon Tap a I
FHENICOLS.
E T Chloramphenicol a % ; >27
NITROIMIDAZOLES
AT Metronidazole T 28 1 16 1 539 T (9) Many non-spore-fomming_gram-posiive anaerobi rods are resistant to mevonidazole

Abbreviations: ATCC®, American Type Culture Collect
concentration; QC, quality control; R, resistant; S, susceptible.

CFU, colony-forming unis); 1, intermediate, LHB, lysed horse blood; MIC, minimal inhibitory

Footnotes
a. ATCC®is a registered trademark of the American Type Culture Collection.

b. AIC: Group A for gram-positive anaerobes and group C for gram-negative organisms. Refer to Table 1C.

Reference for Table 24

1 CLSI. Methods for Antimicrobial Susceptibiliy Testing of Anaerobic Bacteria, Sth ed. CLSI standard M11. Wayne, PA: Clinical and Laboratory Standards

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103

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Table 3A

Tests for ESBLS

Table 3A. Tests for Extended-Spectrum B-Lactamases in Klebsiella pneumoniae, Klebsiella oxytoca, Escherichia coli, and Proteus
mirabilis

NOTE: Following evaluation of PK-PD properties, limited clinical data, and MIC distibutions, revised breakpoints for cefazolin, cefotaxime, ceftazidime,
ceftizoxime, ceftriaxone, and aztreonam were published in January 2010 (M100-S20) and are listed in Table 2A. Cefuroxime (parenteral) was also evaluated;
however, no change in breakpoints was necessary with the dosage. When using the current breakpoints, routine ESBL testing is no longer necessary before
reporting results (ie, itis no longer necessary to edt results for cephalosporins, aztreonam, or penicilins to resistant). However, ESBL testing may stil be useful for
epidemiological or infection prevention purposes. For laboratories that have not implemented the current breakpoints, ESBL testing should be performed as
described inthis table.

Breakpoints for drugs with limited availabilty in many countries (eg, moxalactam, cefonicid, cefamandole, and cefoperazone) were not evaluated. If considering
use of these drugs for E col, Klebsiella pneumoniae, Klebsiella oxytoca, or Proteus mirabilis, ESBL testing should be performed. Ifisolates test ESBL positive,
the results for moxalactam, cefonicid, cefamandole, and cefoperazone should be reported as resistant.

NOTE: Information in boldface type is new or modified since the previous edition.

- en —_—
en u rra mm
a 2 sige — sana A ce
‘concentration | K oxytoca, and £ col: K oxytoca, and E. colt Geftazidime-clavulanate 30/10 19 | Ceftazidime-clavulanate
Cefpodoxime 10 ng or Cefpodoxime 4 ygiml or 0.25/4-128/4 gil.
Ceftazidime 30ugor Ceftazidime — 1 pg/mL or | and
teste nrg | Cas ogi le
Cefotaxime 301g or Cefotaxime — 1hgímLor | Cefotaxime 3019
A A
ee
For P. mirabilis: For P. mirabilis: Meret ad Lee 0.25/4-64/4 pg/mL.
im ge | “Cetacne Dome | pensons Ga sirgben
Cefotaxime 30 Hg \Cefoteegms: Ian; alone and in combination with
(Testing more than one (Testing more than one clavulanate)
Gerona u |
oa | nenes
detection)
aa a a aa
EEE ==
O ann WET ar son
=
a — rue Er ran aan
length

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es Table 3A. (Continued) 3
e Test (Criteria for! e Of ESBL Test ESBL Test El
El Testmethod | Disk difusion Broth microdiution Disk difusion Broth microdiluion E
2 Resume | Fax pneumoniae, K anaes, | Growth ater above he [Az Sen merensemazone A238 wood oncanraln 3
Al and E cof. concentrations listed may | dameter for either antimicrobial | decrease in an MIC for either E
Cefpodoximezone — <17mm. | indicate ESEL production (ie, | agent tested in combination with | antimirobial agent tested in 3
è o rl areas, | Tees | LÉ
E Rateonamzone 27mm | andK oxfoce, MIC=8 | the agent when tested alone=ESBL | the MIC ofthe agent when E
5: Cefotaxmezone <27mm | sigimL forcefpodoxime or | (eg. ceftazidime zone= 16; tested alone ESBL E
3: Comieronezme Sa5™ |MIC=2ugmL for ceftazidime-clavulanate zone=21). | (eg, cetazidme MIC=8 pg/mL; $
E: = ceftazidime, aztreonam, coftazidime-clavulanate
e For P. miabiis cefotaxime, or cattiaxone; MIC=1 git).
Y: Getpodorime zone <22mm | endfor P. mrabl, MIC
ha Ceftazidime zone <22mm | ?21gml for cefpodoxime,
E Cefotaxime zone — <27mm | cefazidime, or cefotaximo)
A Zones above may indicate ESBL
E production
= Reporting For al confirmed ESBL-producing stains:
5 Iflaboratores do not use current cephalosporin and aztreonam
El breakpoints, the test interpretation should be reported as resistant for
E allpenicilis, cephalosporins, and aztreonam.
> Iflaboratories use current cephalosporin and aztreonam breakpoints,
test interpretations fr these agents do not need tobe changed rom
susceptible to resistant.
: E
E Fa

Table 3A

Tests for ESBLS

Table 3A
Tests for ESBLS

= Table 3A. (Continued) ES
& Test Criteria for Performance of ESBL Test ESEL Test E
Testmethod Disk difusion Broth microdilution Disk difusion Broth microdiution 2
ac ‘When testing antimicrobial | When testing antimicrobial | When performingthe ESBL test, | Wen performing the ESBL 3
recommendations | agents used for ESBL agents used for ESBL K pneumoniae ATCC 700603 ' | test K pneumoniae ATCC® A
detection, K pneumoniae detection, K pneumoniae | and E. col ATCC® 25922 should | 700603 and E col ATCC® E
ATCC® 700603 s provided as | ATCC® 700603 is provided as | be used for routine QC (eg, 25922 should be tested
: a supplemental QC strain (eg, | a supplemental OC strain | weekly or daily) routinely (eg, weekly or daily)
: for training, competence (eg, for training, competence
assessment, or test evaluation). | assessment, or test
Either strain, K pneumoniae | evaluation). Ether sain, K
ATCC® 700603 or E. col ‘pneumoniae ATCC® 700603 or

ATCO? 25822, may then be | E coll ATCC® 25822, may
used for routine QC (eg, weekdy | then be used for routine OC

: or dal. (69, weekly or day)

: E. coli ATCC® 25922 (see E coli ATCC® 25922=no Acceptable QC: Acceptable QC:

E accoptable QC ranges in Table | growth (see acceptable QC | £ coffATCC® 25922:<2.mm | E coll ATCC® 25922: <3

: 401) ranges listed in Table SA-1) | increase in zone diameter for | twofold concentration decrease

: ‘antimicrobial agent tested in | in MIC for antimicrobial agent

B ‘combination with clavulanate vs | tested in combination with

z the zone diameter when tested clavulanate vs the MIC of the

: alone. agent when tested alone,

E K pneumoniae ATCC? 700603: | K. pneumoniae ATCC® K pneumoniae ATCC? 700603: | K pneumoniae ATCC?

: Cefpodoxime zone 9-16 mm_ | 700603 = Growth 28 mm increase in zone 700803: 23 twofold
Cefazidme zone 10-18mm | Cefpodoxime MIC 28 pgiml | diameter of cofazidme- concentration decrease in MIC

Adtreonam zone 10-16 mm | Ceftazidime MIC >2 ygimL | clavulanate vs ceftazidime alone; | for an antimicrobial agent
Cefotaxime zone 17-25mm | Aztreonam MIC >2 gmL | 23-mm increase in zone tested in combination with
Cefriaxone zone 16-24mm | Cefotaxime MIC 22 jg/mL | diameter of cafotaxime- clavulanate vs the MIC of the
Coftiaxone MIC =2 sg/mL_| elavulanate vs cefotaxime alone. | agent when tested alone.
‘Abbreviations: ATCC®, American Type Culture Collection; CAMHB, cation-adjusted Mueller-Hinton broth; ESBL, extended-spectrum Pactamase; MHA,
‘Mueller-Hinton agar; MIC, minimal inhibitory concentration; PK-PD, pharmacokinetic-pharmacodynamic:

Footnotes

a. Preparation of ceftazicime-clavulanate (30 19/10 ug) and cefotaxime-clavulanate (30 19/10 ug) disks: Using a stock solution of clavulanate at 1000 igi
(either freshly prepared or taken from small aliquots that have been frozen at -70°C), add 10 y of clavulanate to ceftazidime (30 jig) and cefotaxime (30 ug)
disks. Use a micropipette to apply the 10 L of stock solution to the ceftazidime and cefotaxime disks within one hour before they are applied to the plates,
allowing about 30 minutes for the clavulanate to absorb and the disks to be dry enough for application. Use disks immediately after preparation or discard do
not store,

b. ATCO®is a registered trademark of the American Type Culture Collection.

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For Use With MO2 and MO7

‘M100, 30th ed

This page is intentionally left blank.

Clinical and Laboratory Standards Institute. All rights reserved.

107

EN

pawiasas St JAM SPADIS ÉIOP.OGT PLO Hs

Introduction to Tables 38 and 3C
Tests for Carbapenemases

Introduction to Tables 3B and 3C. Tests for Carbapenemases in Enterobacterales and Pseudomonas aeruginosa

Institutional infection prevention procedures or epidemiological investigations may necessitate identification of carbapenemase-producing Enterobacterales and
PP. aeruginosa. Such testing is not currently recommended for routine ust

Carbapenemase-producing isolates of Enterobacterales usually test intermectate or resistant to one or more carbapenems using the current breakpoints as listed
in Table 2A (NOTE: Testing not susceptible to ertapenem is often the most sensitive indicator of carbapenemase production) and usually test resistant to
fone or more agents in cephalosporin subclass I (eg, cefoperazone, cefotaxime, ceftazidime, ceizoxime, and ceftriaxone). However, some isolates that produce
carbapenemases such as SME or IMI often test susceptible to these cephalosporins.

Laboratories using Enterobacterales MIC breakpoints for carbapenems described in M100-S20 (January 2010) should perform the CarbaNP test, mCIM, CIM,
andlor a molecular assay (refer to Tables 38 and 3C for methods) when isolates of Enterobacterales are suspicious for carbapenemase production based on
imipenem or meropenem MICs 2-4 jigimL or ertapenem MIC 2 ug/mL (refer to Tables 38-1 and 30-1 for guidance on reporting). Aer implementing the current
breakpoints, these additional tests may not need to be performed other than for epidemiological or infection prevention purposes (i, itis no longer necessary to
edit results for he carbapenems to resistant fa carbapenemase producer is detected)

NOTE: Information in boldface type is new or modified since the previous edition.

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81 Introduction to Tables 38 and 3C. (Continued) E
e: "Tests Used for Epidemiological or infection Prevention-Related Testing E
5: Cabane mci AIM With ecım E
8: (Table 38) (rable 30) (Table 3¢) other (eg, molecularassays) | |£
N Organisms Enterobacterales and Enterobacterales and Enterobacterales hat — | Enterobacterales and E
P. aeruginosa thatarenot | Praenuginosa hat arenot_ | arepoativebymciM | P. aeruginosa that are not E
È susceptible to one or more ‘susceptible to one or more susceptible to one or more E
$ carbapenems carbapenems Carbapenems o determine the E
E presence ofa carbepenemase, E
3: Grto determine curbepenemase g
8: type in isolates postive by
gi erbaNP or mM.
53 [reos Rapid o special reagents or media Determines ype of
necessary media necessary carbapenemass in action to
ES absence or presence ofthe
E: enzyme
2 [mins ‘Special reageris are needed, | Requires overnight incubalon | Requires overight | Special reagents and
id some of which necesshate in incubation ecuipment are needed
& hasse preparation (und have a
E shot shall) Specie t targeted genes:
= false-negative resul specie
E Invalid results occur with some Carbapenemase gene present
3 isolates. isnot targeted
El
E Certain carbapenemase types
{ea OXAtype, chremosomaly
tencoded) are not consistently
detected
‘Abbreviations: ci, EDTAmodied carbapenem nactvaion method CIM, mood carbapenem nacivaton method, MIC, minimal mibRory concentran.
NOTE: Information in boldface type is new or modified since the previous econ.
À 5
e Fa

Introduction to Tables 38 and 3C

Tests for Carbapenemases

Tables 38 and 38-1

CarbaNP Test for Suspected Carbapenemase Production and Modifications When Using MIC
reakpoints Described in M100-520 (January 2010)

Table 3B. CarbaNP Test for Suspected Carbapenemase Product Enterobacterales and Pseudomonas aeruginosa!”

on

NOTE: If using FORMER MIC breakpoints for carbapenems described in M100-S20 (January 2010), please refer to modifications in
Table 38-1 below.

Po oe Dorn

Test CarbaNP Test

When to perform this test | For epidemiological or infection prevention purposes. NOTE: No change in the interpretation of carbapenem susceptibility test
results is necessary for CarbaNP-positive isolates. Such testing is not currently recommended for routine use.

Test method. Colorimetric microtube assa

Test reagents and + Clinical laboratory reagent water

materials + Imipenem reference standard powder

+ Commercially available bacterial protein extraction reagent in Tris HCI buffer, pH 7.4

+ Zinc sulfate heptahycrate

+ Phenol red powder

1 N NaOH solution
10% HCI solution

Microcentifuge tubes 1.5 mL, clear
Azul inoculation loops.

Containers to store prepared solutions

Use reagents above to prepare the following solutions (instructions for preparation are provided below this table
10 mM zinc sulfate heptahydrate solution

0.5% phenol red solution

0.1 N sodium hydroxide solution

CarbaNP Solution A

CarbaNP Solution B (solution A-+imipenem)

Label two microcentrifuge tubes (one “a” and one D) for each patient isolate, OC organism, and uninoculated reagent
control

‘Add 100 pL of bacterial protein extraction reagent to each tube

For each isolate to be tested, emulsity a 1-ul loopful of bacteria from an overnight blood agar plate in both tubes “a” and “b.”
Vortex each tube for 5 seconds. (Uninoculated reagent control tubes should contain only bacterial protein extraction
reagent, no organism.) NOTE: Do not use growth from selective media or plates containing antibiotics or other agents that
Select for certain bacteria

‘Add 100 ul of solution Ato tube “a.”

‘Add 100 pL of solution B to tube “b.”

Vortex tubes well

Incubate at 35°C + 2°C for up to 2 hours. Isolates that demonstrate positive results before 2 hours can be reported as
carbapenemase producers.

Test procedure

ENT

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Tonner Ton

PA SG ES FO SORE IIo PAI MERA Cl CUE Ne: | | à

4! E
S El
E Strategy for reading (see Figure 1, below) 2
= +. Read uninoculated reagent contro tubes “a” and “bie, “blanks. E
+ Both tubes must be red or red-orange. E
a + Feith tube is any other color, the testis invalid. E
a 2. Read inoculated tubs“ E
x + Tube ‘a’ must be red or red-orange. $
E + tube “ais any other color, the test
$ a essed
+ Red orrechorange =negative
= © Light orange, dark yellow, or yelow=postive
E + Orange=invalid
5
Li A Interpret rois as facie:
5: its for Patient and QC Tubes.
El Tube “a”:
El Solution A Tube “br:
E (serves as internal control) Solution B
Red or red-orange Red or red-orange Negativo, no
arbapenemase detected
Redorredorange Light orange, dark yellow, or | Positive, carbapenemase
yellow producer
Redor red-orange Orange Invalid
Orange, light orange, dark Any color invalid
yellow, or yellow
E
E
E
a

Tables 38 and 36-1

CarbaNP Test for Suspected Carbapenemase Production and Modifications When Using MIC
Breakpoints Described in M100-520 (January 2010)

Tables 38 and 38-1
CarbaNP Test for Suspected Carbapenemase Production and Modifications When Using MIC

reakpoints Described in M100-520 (January 2010)

ES Table 3B. (Continued) E
=: Test CarbaNP Test El
: “Test interpretation NOTES: E
(Continued) 3
E A slight color change may be observed with the action of imipenem to solution A. Compare patient tubes to the uninoculated E
$ reagent control tubes when interpreting questionable results. &
For invalidresuts:
+ Check reagents for OC strains and uninoculated reagent controls.
Reagent deterioration can cause invalid results. An invalid result for an uninoculated reagent control test indicates a problem
q with solution A andlor solution B. Check the pH of solution A. IfpH is <7-8, prepare fresh solution A and solution B.
: + Repeat the test, including the uninoculated reagent controls
3 + Ifthe repeat testis invalid, perform molecular assay.
Reporting Report posiive as "Carbapenemase producer”
5 Report negative as No carbapenemase detected”
g: ‘QC recommendations | Test positve and negative QC strains and uninoculated eagant control tubes each day oftesing,
E: K pneumoniae ATCC® BAA-1705"—Carbapenemase positive
7 K pneumoniae ATCC? BAA-1708""—Carbapenemase negative
E:
: Results for uninoculated reagent control tubes “a” and “b” must be negative (ie, red or rectorange). Any other result invalidates
all tests performed on that day withthe same lot of reagents.
El i The addition of imipenem to tube *b' might cause tube “b” to appear red-orange when tube “a” is red.
& 5 Abbreviations: ATCO” American Type Culture Collection; MIC, minimal inhibory concentration; pH, negative logarithm of hydrogen fon concentran; OC, qua
E: control.
$: Footnote
À à. arcotisarepitedrasomak ofthe Amen Type Cute Colecon Pa ATCC®conenten, he ademak sym use ter "BA in ech catalog
gi number, in conjunction with Ihe registered ATCC? name. 7
8: E
a
3: El
E: 2
5: ©
2! E
E E
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gc Table 3B. (Continued) El
8: El
sl NOTE 1: Test recommendations were largely derived following testing of US isolates of Enterobacterales and P. aeruginosa and provide for a high level of €
E: sensitivity (> 90%) and specific (> 90%) in detecting KPC, NDM, VIM, IMP, SPM, and SMEtype carbapenemases in these islates. The sensitivity and specificity El
N ofthe tet for detecting other crbapenemaseproducton cn vary. Ti aly of his test, a isted in ine above procedure, to detect OKA BÄNKE producers E
is poor! A
ASAS (L
3 was susceptible to meropenem and intermediate to imipenem and ertapenem) were not detected by this test, 3
3: 3
e: NOTE 3: Additional investigations of CarbaNP with Acinetobacter spp. showed poor sensitivity (ie, 21.3% for A. baumanni); therefore, the previous
8: recommendation for use of CarbaNP with Acinetobacter spp. was removed,
À nome mémo ine rodar ars
8:
E
È
5
El
El
2
A
: E
i 3
est d

Tables 38 and 38-1

CarbaNP Test for Suspected Carbapenemase Production and Modifications When Using MIC
Breakpoints Described in M100-520 (January 2010)

Tables 38 and38-1

CarbaNP Test for Suspected Carbapenemase Production and Modifications When Using MIC
reakpoints Described in M100-520 (January 2010)

=; Table 3B-1. Modifications of Table 38 When Using MIC Breakpoints for Carbapenems Described in M100-S20 (January 2010)'* =
= Test CarbaNP Test E
À Whentoperformthistest: | Until laboratories can implement the revised carbapenem MIC breakpoints, this test (or an alternative confirmatory test for
carbapenemases) should be performed when isolates of Enterobacterales are suspicious for carbapenemase production E
based on imipenem or meropenem MICs of 2-4 jyg/mL or ertapenem MIC of 2 ug/mL. 8
Reporting For isolates that are CarbaNP positive, report all carbapenems as resistant, regardless of MIC. Lag
If the CarbaNP test is negative, interpret the carbapenem MICs using CLS! breakpoints as listed in Table 2A in M100-S20
(January 2010)
If the CarbaNP test is negative, interpret the carbapenem MICs using CLSI breakpoints as listed in Table 2A in M100-S20
January 2010).
: NOTE: Not allcarbapenemase producing isolates of Enterobacterales are CarbaNP positive.
1 Abbreviaion: MIC, minimal inhibitory concentration
3 Tables 38 and 3B-1 - Instructions for Preparing Test Components
2 me steps for preparing 10 mM zinc sulfate heptahyckate solution are listed below.
Step Action Comment
: 1 | Weigh out 14 g of ZnSO: 7H20.
8: 2 | Acte powder to 500 ml dinical laboratory reagent water
$: 3] Mix the solution.
E: 4 | Store the solution at room temperature Expiration is 1 year or not to exceed expiration ofindvidual
i: components
È : The steps for preparing 0.5% phenol red solution are listed below.
Si D ation en
q: EA ‘Weigh out 1.25 g of phenol red powder.
& 2 [2] Adatie powder to 250 ml cinial laboratory reagent water.
Li [TS icine souton
Ze Hu ‘Store the solution at room temperature Expiration is À year or nat to exceed expiration of individual
Si components.
8: m
Ê: NOTE: This solution does not remain in solution, Mix wel before use. E
El ‘The steps for preparing 0.1 N sodium hydroxide solution are listed below. E
&: E
E ‘Step Action ‘Comment 3
3: 1 | Add20mL of TN NaOH to 180 mL cinical laboratory reagent water. E
s: 2 ‘Store the solution at room temperature. Expiration is 1 year or not to exceed expiration of individual Es
à components. E

$
E
3
:
E
3
E
A
È
5
E
È
5
3
E
E
E

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Tables 38 and 38-1. (Continued)
‘The steps for preparing CarbaNP solution A are listed below.

Step Action

‘Comment

1 | Toa 25-to S0-ml beaker, add 2 mL of 0.5% phenol red solution to 16.6

mL clinical laboratory reagent water.

2_| Add 180 uL of 10 mM zinc sulfate solution.

3 | Adust the pH fo 7.80.1 with 0.1 NNaOH solution (or 10% HOT 10% HOT solution can be used ifthe pH Is too high,
solution if pH is too high).

4 | Store the solution at 4 to 8°C In a small vial or Batlle, Protect the solution from prolonged light exposure

Expiration is 2 weeks or not to exceed expiration of individual components
(solution should remain red or rec-orange; do not use if solution turns any
other color)

The steps for preparing CarbaNP solution B (solution A+6 mg/mL imipenem) are listed below.

Step ‘Action

‘Comment

‘| Determine the amount of solution E needed, allowing 100 pL per tube
for each patient, QC strain, and uninoculated reagent control.

Example: To test 2 patient isolates, positive and negative controls and an
uninoculated reagent control, 500 pL of solution Bis needed.

2 | Weigh out approximately 10-20 mg of imipenem powder.

Itis advisable to weigh out atleast 10 mg of powder. Divide the actual
weight by 6 to determine the amount (in mL) of solution A to add to the
powder.

Example: 18 mg of imipenem /
for 30 tubes.

‘mL of solution A, which is sufficient

3__| Store the solution at 4to 8°C for up to 3 days.

NOTE: Information in boldface type is new or modified since the previous edition

CarbaNP Test for Suspected Carbapenemase Production and Modifications When Using MIC

Tables 38 and 36-1

kpoints Described in M100-520 (January 2010)

ONPE CONTIN STO

Po Oe DOUX

Tables 38 and 38-1
CarbaNP Test for Suspected Carbapenemase Production and Modifications When Using MIC

reakpoints Described in M100-520 (January 2010)

5 Tables 3B and 3B-1. (Continued) =
: 3
: Postve test Negative est $
; Pa . ha . ta
3 | \
À Bank control invalid tet
: a 8 Pa .
E v | i
E
8: etre invalid Positive
a: A
E: |
E n= = AA
E M
: LEE E ee | !
FS Re Red: “Orange Orange Tight Yellow E
= orange orange yelow E
E Figure 1. Interpretation of Color Reactions 3
z 2
3 a
3 2
Ri El

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