GNB reporting gram negative bacilli reporting -.pptx

About gram negative bacilli reporting

1. INTERPRETATION OF AST: REPORTING OF GNB

2. Recording of zone diameter Reporting of Enterobacterales Specific β lactamase resistance mechanisms Cefazolin Cefepime , Piperacillin and Piperacillin Tazobactam Colistin Fosfomycin Tigecycline Shigella & Salmonella Fluoroquinolones and Salmonella Imipenem & Proteae OVERVIEW N onfermenters P. aeruginosa Acinetobacter sp Stenotrophomonas maltophilia & Burkholderia cepacia complex Burkholderia pseudomallei O ther non enterobacterales O ther glucose fermenting GNB Aeromonas Vibrio

3. Accurate interpretation of AST clinical team in initiating appropriate antimicrobial for targeted therapy Also preparing antibiogram , infection control purposes Clinical Laboratory Standard Institute(CLSI) & European Committee On Antimicrobial Susceptibility Testing(EUCAST) – widely used guideline worldwide Lab – free to choose breakpoint from CLSI/ EUCAST – must not use them interchangeably INTRODUCTION

4. Preferential approach 1 st preference – lab should adapt breakpoints from any one guideline for all organism / antimicrobial agents ( eg:CLSI ) 2 nd preference – only for organism / antimicrobial agents ,if breakpoints are not available from 1 st preference , can follow other guideline ( eg : EUCAST) 3 rd preference – breakpoints not available in CLSI and EUCAST, breakpoint from FDA can be followed ( eg : Tigecycline ) 4 th preference- if FDA also doesn’t meantion about breakpoint ( eg : cefoperazone - sulbactam ) article based breakpoints may be followed

5. Zone diameter should be recorded Lab should interpret the zone using written chart rather than with memory recall Every lab should prepare written breakpoint chart customized to common organism – antimicrobial agent tested using std guidelines Interpreting result by an approximate idea (bigger/smaller zone ) without measuring – strictly prohibited Zone diameter breakpoint differ among different organisms. RECORDING OF ZONE DIAMETER

6. ENTEROBACTERALES

7. As per CLSI & EUCAST – additional testing for resistance mechanism detection & subsequent editing of results from S to R not necessary Isolates tested S but positive for β lactamases should be reported as S β lactam breakpoints ( cephalosporins , aztreonam , carbapenems ) are revised –it detect all resistance mechanisms REPORTING OF SPECIFIC β LACTAMASE RESISTANCE MECHANISMS

8. Rpt AST (after 3days) for Amp c producers (SPICE organisms) – develop resistance to beta lactams during therapy Carbapenemase detection – not reported with susceptibility report of various carbapenems Need for further therapeutic options MIC-based Carbapenemase gene detection

9. REPORTING OF CEFAZOLIN - three types of cefazolin breakpoints available Breakpoint for systemic infections Breakpoint for u ncomplicated UTI due to E.coli , K.pneumoniae , P.mirabilis 2g Q 8H for systemic infection 1g Q 12H for uncomplicated UTI Parenteral breakpoints for Cefazolin Oral breakpoints for Cefazolin only for uncomplicated UTI due to above organisms

10. If cefazolin is – Sensitive Resistant Oral cefazolin breakpoints used as surrogate for oral cephalosporins ( cefaclor , cephalexin , cefprozil , cefuroxime & loracarbef )  for treating uncomplicated UTI ( E.coli , K.pneumoniae , P.mirabilis ) These drugs individually tested

11. Have SDD breakpoints for Enterobacterales as per CLSI Well established literature supported widely used, approved increased dose regimens available for treatment of infection caused by isolates with SDD results. REPORTING OF CEFEPIME, PIPERACILLIN AND PIPERACILLIN TAZOBACTAM

12. Breakpoints available for – Enterobacterales , P. aeruginosa , Acinetobacter baumannii complex in EUCAST, CLSI EUCAST - has breakpoint for other Acinetobacter sp and other Pseudomonas sp Breakpoint values for CLSI are same as EUCAST, except for P. aeruginosa Colistin & polymixin B are equivalent agents  Colistin results can be extrapolated for polymixin B Colistin – only I & R categories are available(CLSI) REPORTING OF COLISTIN

13. COLISTIN TESTING Testing methods broth microdilution (KBDD , E test – not acceptable) for testing Colistin sulfate for treatment Colistin methane sulfonate

14. COLISTIN WARNING COMMENTS Dosage Given with loading dose & max renally adjusted doses or max recommended doses resp. Restricted use only Use of Polymyxin should be avoided. Alternative active agents should be preferred, if available Combination therapy For systemic infections , should be used in combination with another active antimicrobial. Monotherapy should be avoided Inhaled and systemic polymyxin combination Preferred over systemic polymyxin for pneumonia

15. IR – Acinetobacter sp, Stenotrophomonas , B.cepacia Testing methods – agar dilution, KBDD Broth dilution & E test – should not be performed CLSI -DD & MIC breakpoints available for urinary isolates of E.coli & Enterococcus faecalis REPORTING OF FOSFOMYCIN

16. ENTEROBACTERALES PSEUDOMONAS Separate breakpoints for oral & parenteral Only ECOFF breakpoint is available DD & MIC breakpoints available only for urinary isolates of E.coli & Enterococcus faecalis Urinary isolates of E.coli - DD & MIC breakpoints available for oral fosfomycin DD BP for parenteral - only for E.coli from any site STAPHYLOCOCCUS MIC breakpoints for parenteral Fosfomycin – all Enterobacterales (any clinical specimen) Only MIC breakpoints for parenteral Fosfomycin (no breakpoint for oral Fosfomycin ) EUCAST (FOSFOMYCIN)

17. No CLSI breakpoint EUCAST – breakpoint only for E.coli & Citrobacter koseri For Enterobacterales , FDA breakpoint – applicable for all organisms For Acinetobacter sp – breakpoint not available in both EUCAST & FDA Acintobacter baumannii - breakpoint from an article source, used in automated AST system ( Pachon – Ibanez et al ) REPORTING OF TIGECYCLINE

18. Typhoidal Salmonellae, Shigella – AST indicated for extraintestinal & intestinal isolates. NTS routine AST - only for extraintestinal isolates Clinically ineffective agents – for Salmonella & Shigella 1 st & 2 nd gen cephalosporins , cephamycins & aminoglycosides appear susceptible in vitro but not effective clinically Should not be tested or reported as susceptible REPORTING OF SHIGELLA & SALMONELLA

19. Amoxicillin for Shigella - When reporting ampicillin results –comment  treatment of shigellosis with amoxicillin might not be comparable to ampicillin , with poorer efficacy Azithromycin except Shigella & Salmonella other Enterobacterales are IR – no BP Azithromycin BP Shigella - DD zones can be hazy – confirmed by MIC Salmonella – breakpoint only available for S.Typhi (not for other serotypes)

20. MIC breakpoints available – ciprofloxacin, levofloxacin , ofloxacin DD breakpoints available - ciprofloxacin, pefloxacin Higher breakpoints are set (higher zone diameter and lower MIC ) clinical evidence of poor response in systemic infections by Salmonella sp with low level FQ resistance FLUOROQUINOLONES AND SALMONELLA

21. Test preference for reporting FQs 1 st choice- Ciprofloxacin MIC prefered test for Salmonella sp. Levofloxacin and ofloxacin MIC - performed if they are used for therapy 2 nd choice – if MIC methods not available Pefloxacin DD screening - surrogate test to predict ciprofloxacin susceptibility . Pefloxacin will not detect resistance in Salmonella sp due to aac (6’)- Ib-cr 3 rd choice Ciprofloxacin DD Cannot reliably detect low level resistance in Salmonella sp. Least preferred method

22. Tribe Proteae – elevated MIC against imipenem (intrinsically low activity of drug) EUCAST – only R breakpoints( no S breakpoint ) of imipenem Imipenem susceptible result need to be reported only as SIE Always used in increased dosage for treatment against tribe Proteae IMIPENEM & PROTEAE

23. NONFERMENTERS

24. Cystic fibrosis - need extended incubation (24hrs) before reporting as susceptible Repeat testing- develop resistance during prolonged therapy Initial susceptible become resistant in 3-4days after therapy. Non- aeruginosa sp CLSI breakpoint table for pseudomonas applies to P. aeruginosa only. CLSI uses I breakpoint for betalactams , aminoglycosides and quinolones For other species follow “other enterobacterales ”- only MIC breakpoints . EUCAST – breakpoint table for pseudomonas applies to all species P. aeruginosa

25. CLSI colistin breakpoint for Acinetobacter applies to A.baumannii complex only . EUCAST – breakpoint for Acinetobacter is applicable for all species Acinetobacter sp

26. Both are IR to majority of antimicrobial agents CLSI – available for limited range of agents EUCAST – has breakpoint only for cotrimoxazole Stenotrophomonas maltophilia & Burkholderia cepacia complex

27. EUCAST – DD & MIC for most of the antimicrobials used for treatment of melioidosis CLSI (M45) – only MIC breakpoints for limited agents(not for meropenem ) Thailand study group named Mahidol Oxford Tropical Medicine Research Unit (MORU)- DD breakpoints Burkholderia pseudomallei

28. Organisms covered- Pseudomonas sp other than P.aeruginosa Elizabethkingia meningoseptica , E.anopheles Achromobacter , Chromobacterium violeceum , Ralstonia , Sphingomonas . Organisms not covered - nonfastidious , glucose non fermenting Stenotrophomonas maltophilia , Burkholderia , P.aeruginosa , Acinetobacter sp Other glucose fermenting – Aeromonas , Vibrio fastidious gram negative org – Haemophilus , HACEK, Brucella , Neisseria , Moraxella , Campylobacter, Helicobacter, Pasteurella OTHER NON ENTEROBACTERALES

29. CLSI Only MIC breakpoints are available KBDD – not recommended EUCAST – DD and MIC breakpoints for non aeruginosa and Achromobacter for a limited set of agents

30. OTHER GLUCOSE FERMENTING GNB

31. Glucose fermenting GNB other than Enterobacterales frequently obtained from clinical specimens – Aeromonas , Vibrio Breakpoints- CLSI M45,EUCAST

32. Applicable for A.caviae complex, A.hydrophilia complex & A.veronii complex AST testing limited to extraintestinal isolates Aeromonas spp – resistant to ampicillin , ampicillin-sulbactam,amoxicillin – clavulanate & cefazolin Aeromonas - possess inducible β lactamases & resistance may emerge during therapy with β lactam - repeat AST after 3days. Treatment failure – noted with elevated ciprofloxacin MIC(but susceptible) Aeromonas

33. Breakpoint in CLSI M45 are derived from CLSI M100 Enterobacterales CLSI M45-not updated after 2018 CLSI M100 Enterobacterales breakpoints revised for quinolones (ciprofloxacin & levofloxacin ) & Piperacillin-Tazobactam Authors suggest to use current CLSI M100 Enterobacterales breakpoints for above agents in Aeromonas

34. EUCAST , CLSIM45 CLSI M45 breakpoint are derived from CLSI M100 Enterobacterales Azithromycin adapted as per staphylococcus breakpoint Final inoculum – prepared in 0.85% NS No need to add supplemental NaCl to medium AST – only for extraintestinal isolates Vibrio sp CLSI EUCAST Antimicrobials tested is different for V.cholerae & other vibrio species Breakpoints are valid for both V.cholerae & other vibrio species

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