CLSI 2021.pptx

CLSI 2021

1. CLSI 2021 Dr Chinmoy Sahu

2. About CLSI Clinical and Laboratory Standards Institute ( Previously NCCLS) International, voluntary, educational, not-for –profit , interdisciplinary organization Accredited by American National Standards Institute Guidelines are formulated to improve diagnostic health care

3. CLSI Workflow CLSI subcommittee on antimicrobial susceptibility testing develops interpretative criteria and quality standards committee- guidelines- Voluntary expert committee - recommendations

4. CLSI Vs FDA CLSI tests investigational drugs FDA may/may not change after CLSI changes Review is done by FDA if changes occur Industry people must follow FDA

5. EUCAST is organised by European Society for Clinical Microbiology and Infectious Diseases (ESCMID), European Centre for Disease Prevention and Control (ECDC), Active national antimicrobial breakpoint committees in Europe. EUCAST was established by ESCMID in 1997 , -> restructured in 2001-2002 and has been in operation in its current form since 2002. Financed by - ESCMID - National Breakpoint committees in Europe

6. Europe had a number of different breakpoints – setting authorities….and therefore different breakpoints….. Breakpoint committees 2016

7. Disc test from EUCAST and CLSI EUCAST Mueller Hinton Inoculum 0.5 McF Incubation 16-20 +/_2h MH + 5% Horse blood and 20 mg β – NAD for fastidious organism Disc strengths QC strains and reference ranges CLSI Mueller Hinton Incubation 18 +/_2h Disc strengths QC strains and reference ranges Presence of Intermediate and susceptible dose dependent category Recent introduction of Epidemiological cut off New screening methods for CRE

8. Staphylococcus species EUCAST vs. CLSI (EUCAST 2017, CLSI 2017) ANTIMICROBIAL EUCAST(mg/L) CLSI (mg/L) S ≤ R> S I R CEFTAROLINE 5 μg S.aureus only ≥20mm ≤20mm - MIC ≤1 >1 - Ceftobiprole 5 μg S.aureus only ≥17mm ≤17mm - MIC ≤2 >2 - Ciprofloxacin 5 μg ≥21mm ≤21mm ≥21 16-20 ≤15 24 24CONS MIC ≤1 >1 ≤1 2 ≥4 levofloxacin5 μg ≥22mm ≤22mm ≥17 14-16 ≤13 MIC ≤1 >1 ≤2 4 ≥8 Gentamycin 10μg ≥18mm ≤18mm ≥15 13-14 ≤12 MIC ≤1 >1 ≤4 8 ≥16 Amikacin3 0μg ≥18mm ≤16mm ≥17 15-16 ≤14 MIC ≤8 >16 ≤16 32 ≥64

9. EUCAST and CLSI are different EUCAST CLSI Established 1997 1970 Membership Representatives of national breakpoint committtes & medical profession Medics, science, industry, regulators Relation to regulator Dialogue with ECDC, EMEA 5-6 meetings per year 2 meeting per yr Relation to industry Consultation with industry Full members Decisions Consensus Voting (www.eucast.org , www.clsi.org)

10. EUCAST and CLSI are different EUCAST CLSI Work Sets breakpoints for European Medicines Agency, Advices ECDC,EFSA US-FDA sets breakpoints Funding ECDC, ESCMID National committees Industry and sales Outputs ECOFF, CBs,Resistance Detection,Expert rules Gradually included some this year Rationales Published Not published Documents Free download For sale(member/non member fee

11. CLSI Vs FDA CLSI tests investigational drugs FDA may/may not change after CLSI changes Review is done by FDA if changes occur Industry people must follow FDA

12. General points Group A – routine primary testing Group B- primary testing but selectively ( group A resistant, polymicrobial infections, drug allergy, intolerance) Group C- multidrug resistant drugs very common Group U- primarily urinary use only Group O- clinical indication but not routinely tested in USA Group Inv. – not approved by FDA

13. General points Susceptible: ( S) resulting in likely clinical efficacy Susceptible dose-dependent ( SDD): Susceptibility is dependent on dosing regimen Cefepime - Enterobacterales Cefaroline - Staphy lococcus aureus Daptomycin - Enterococcus faecium

14. Intermediate (I): response lower than susceptible isolates Resistant: ( R) Isolates not inhibited by usually achievable concentrations or specific resistance mechanisms Nonsusceptible : (NS): absence or rare occurrence of resistant strains

15. Definitions Routine test: tests for routine clinical testing Supplemental test : methods other than routine disk diffusion and dilution Screening tests : presumptive tests and need additional testing Surrogate agent testing : replaces drug of interest Equivalent agent testing : predicts result of closely related drugs of same class

16. Supplemental test ( Required)

17. Supplemental test ( Optional)

18. Supplemental Test Colistin agar test: Enterobacterales and Pseudomonas aeruginosa : determining colistin resistance Colistin broth disk elution test:Enterobacterales and Pseudomonas aeruginosa : determining colistin resistance

19. Screening Test

20. Surrogate Test

21. Test with equivalent agents

22. How to use

23. Added azithromycin Disc diffusion and MIC breakpoint for Shigella spp Shigella Salmonella S= 16 or more 13 or more I= 11 to 15 R= 10 or less 12 or less S= 8 or less 16 or less I= 16 R= 32 or more 32 or more

24. Treatment of Shigella First line: Fluroquinolones Second line: Beta lactams , Cephalosporins Now azithromycin can be used as second line agent where resistance to fluroquinolones high and among macrolides , azithromycin preferred

25. Added azithromycin disc diffusion breakpoint for N.gonorrheae S= more than 30 S= MIC 1 or less Treatment: Ceftriaxone 500 mg IM single dose Gentamicin 240 mg IM single dose plus azithromycin 2 gm orally single dose

26. Added Imipenem-relebactam disc diffusion and MIC breakpoint for Enterobacterales and Pseudomonas aeruginosa MIC breakpoints for Anaerobes Enterobacterales Pseudomonas aeruginosa S = 25 or more S= 23 or more I= 21-24 I= 20-22 R= 20 or less R= 19 or less S= 1/4 S= 2/4 I= 2/4 S= 4/4 R= 4/4 or more S= 8/4

27. Beta Lactamase Inhibitors Protects beta lactam antibiotics from enzymatic hydrolysis Current ones- active against Class A beta lactamases Poor activity against class C and D enzymes Newer agents – activity against class C and D enzymes, with Carbapenems increase activity against MBLs

28. Relebactam There are six betalactamse inhibitors: Sulbactam , clavulanic acid, tazobactam , avibactam , vaborbactam , Relebactam Relebactam inhibits class A carbapenemases but not class B or D Oxa Used for MDR Gram negative organisms Imipenem-relebactam used in cUTI , cIAI , VAP

29. Added ceftolozane-tazobactam MIC breakpoints for H.influenzae and H.parainfluenzae S= 0.5/4 or less Treatment : ceftriaxone or cefotaxime for meningitis azithromycin or quinolones for mild infections

30. Ceftolozane / Tazobactam Novel oxyimino-aminothiazolyl cephalosporin and betalastamse inhibitor combination MOA- novel cephalosporin and inhibitor combination Organism profile – P. aeruginosa ( cephalosprin and carbapenem resistant ones) E.coli and Klebsiella

31. Ceftolozane / Tazobactam Clinical Uses- complicated intrabdominal infections , complicated UTI Advantages : Good antipseudomonal activity Status- FDA approved ( 2014)

32. Added Lefamulin disc diffusion and MIC testing for Staphylococcus spp , H.influenzae , H.parainfluenzae and S.pneumoniae H.Influenzae H.parainfluenzae S= 17 or more S= MIC 2 or less S. aureus S= 23 or more S= MIC 0.25 or less S.pneumoniae S= 17 or more S= 0.5 or more

33. Pleuromitilin compounds Natural product antibiotic ( 1950s) first used in veterinary infections Retapumilin : first human use ( topical) Organism profile: organisms infecting skin and respiratory infections MOA : Inhibit bacterial protein synthesis Newer Compounds : Lefamulin ( BC 3781)

34. Lefamulin Active against atypical organisms and Staphylococcus aureus Also Enterococcus spp Used for CABP, skin and soft tissue infections No cross resistance between other antibiotics for Gram positive bacteria

35. Separated breakpoints of oral and parenteral cefazolin Oral cutoff ( Surrogate test for other oral agents like cefaclor , cefpodoxime for UTI) S= 15 or more R= 14 or less S= 16 or less R= 32 or more Parenteral cutoff S= 23 or more I= 20 -22 R= 19 or less S= 2 or less I= 4 R = 8 or more

36. Revised oxacillin breakpoints for Staphylococcus spp except S.aureus And S.lugdunensis Oxacillin S = 18 or more Oxacillin R= 17 or less Oxacillin MIC S= 0.5 or less Oxacillin MIC R= 1 or more Cefoxitin S= 25 or more Cefoxitin R= 24 or less

37. m ecA and mecC mecA : Cefoxitin R, Oxacillin R mecC : Cefoxitin R, Oxacillin S

38. Clarified the interpretative category of intermediate S: sensitive I: Intermediate ( ˄ concentrates in urine): ampicillin , ticarcillin , TZP, carbapenems , ceftaroline , cefalosporins , aminoglycosides , fluoroquinolones SDD: Susceptible dose dependent R: Resistant NS: Not susceptible

39. Statement for isolates for which there are not current CLSI cut off Only the microorganism listed in the table should be reported. If FDA susceptibility test interpretative criteria ( STIC) is there, it can be used

40. Warning of reporting of antibiotics for use in CSF isolates Agents only given by oral route, 1 st and 2 nd generation cephalosporins , cephamycins , Doripenem , imipenem , ertapenem , lefamulin , clindamycin , macrolides , tetracyclines , Fluoroquinolones : should not be reported in CSF

41. Positive blood cultures as inoculum Ampicillin , aztreonam , ceftazidime , ceftriaxone , tobramycin , Trimethoprim-sulfamethoxazole : can be reported

42. Staphylococcus aureus testing for linezolid and tedizolid Organisms that are susceptible to linezolid also susceptible to tedizolid But organisms that are resistant to linezolid may be susceptible to tedizolid

43. Oxazolidinones New class of synthetic drug with 2-oxazolidine ring Organism profile - multiple resistant Gram positives ( VRE,MRSA) Act on ribosomal 50s subunit Good penetration and accumulation in tissue Linezolid - already used

44. Tedizolid phosphate After oral or IV administration rapidly change to active form Organism profile: better activity than Linezolid in Staphylococcus, Streptococcus, Enterococcus Active against Linezolid and Daptomycin reistant bacteria PK/PD: once daily administration Safety profile: no myelosuppression

45. Tedizolid phosphate No inhibition of Monoamine Oxidase Clinical Use: for SSTIs Status: FDA approved ( 2014)

46. Colistin test for Enterobacterales and Pseudomonas aeruginosa For colistin = broth microdillution , colistin broth disc elution test ( CBDT), colistin agar test For polymyxin = only broth microdilution test

47. Colistin interpretation For Enterobacterales and Pseudomonas aeruginosa I = 2 or less R= 4 or more

48. Discrepancy Issues Table Phenotypic 1 Phenotypic 2/Genotypic Action Reporting Cefoxitin R Latex Agglutination/ mecA positive N/A MRSA Cefoxitin S Latex Agglutination/ mecA negative N/A MSSA Cefoxitin R Latex Agglutination/ mecA negative Confirm ID, repeat Tests If discrepancy not resolved, report MRSA Cefoxitin S Latex Agglutination/ mecA Positive Confirm ID, repeat Tests If discrepancy not resolved, report MRSA

49. Thank You