(and breakpoint table, MIC and. by author. ESCMID Online Lecture Library. conventions) ECCMID 2011, Milan

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1 EUCAST definitions (and breakpoint table, MIC and zone distribution ib ti website ECCMID 2011, Milan conventions) Derek Brown

2 Clinically susceptible/resistant A microorganism is defined as susceptible by a level of antimicrobial activity associated with a high likelihood of therapeutic success A microorganism is defined as resistant by a level l of antimicrobial i activity it associated with a high likelihood of therapeutic failure.

3 Clinically intermediate A microorganism is defined as intermediate t by a level l of antimicrobial i activity associated with uncertain therapeutic ti effect. It implies that an infection due to the isolate may be appropriately treated t in body sites where the drugs are physically concentrated or when a high dosage of drug can be used (In susceptibility testing it also indicates a buffer zone that should prevent small, uncontrolled, technical variation from causing major discrepancies in interpretation)

4 Clinical breakpoints a microorganism is categorized as susceptible (S), intermediate (I) or resistant (R) by applying the appropriate breakpoint in a defined phenotypic test system MICs are the primary breakpoints Breakpoints in other methods are correlated with MIC breakpoints

5 Breakpoints and cut-off values Clinical breakpoints Non-species-related breakpoints Epidemiological cut-off value (ECOFF)

6 Non-species-related breakpoints Pk/Pd (pharmacokinetic/pharmacodynamic) breakpoints Used in clinical breakpoint development Can be a guide to interpretation in situations where there is no species-specific clinical breakpoint

7 Epidemiological cut-off value (ECOFF) MIC value identifying the upper limit of the wild type population A microorganism is defined as wild type (WT) for a species by the absence of acquired and mutational mechanisms of resistance to the agent.

8 EUCAST wild type and ECOFF Wild type ECOFF

9 EUCAST wild type and ECOFF Wild type ECOFF

10 Epidemiological cut-off values (ECOFFs) Estimated by visual inspection or statistically calculated (Turnidge et al CMI 2006;12:418-25) The ECOFF is not changed by sampling time, source (human, animal, environmental), geographical origin Used in clinical breakpoint development and as a sensitive indicator of resistance development in surveillance studies.

11 Relationship between the clinical breakpoints, non-species-related breakpoints and ECOFFs Non-species-related breakpoints will be same as clinical breakpoints unless they split the wild type or there is no resistance There is no definitive relationship between clinical breakpoints and ECOFFs

12 Clinical breakpoint higher than ECOFF Non-sp-related BP S ECOFF R Non-sp-related BP S breakpoint R breakpoint

13 Clinical breakpoint same as ECOFF Non-sp-related BP S R Non-sp-related BP S/I and R breakpoint ECOFF

14 Clinical breakpoint lower than ECOFF Non-sp-related BP S S breakpoint RNon-sp-related BP ECOFF R breakpoint

15 ECOFF and zone diameters ECOFF Wild type

16 EUCAST breakpoint tables v 1.3

17 EUCAST breakpoint table notes Highlight g indicates change since last version

18 EUCAST breakpoint format S, R > MIC R>4 mg/l 8 mg/l Zone R<24mm 23 mm S 1, R >4 Susceptible I Resistant Susceptible I 4 8 S 1, R Resistant

19 EUCAST intermediate category Intermediate category is not displayed e.g. Ciprofloxacin S 0.5 5mg/L, R>1mg/L, Intermediate inferred >0.5-1 mg/l S 22 mm, R<18 mm, Intermediate inferred mm

20 EUCAST table abbreviations - Susceptibility testing not recommended as the species is a poor target for therapy with the drug (do not test, or do not report, or report as R) IE Insufficient i evidence to set a breakpoint (report MIC values with comment but no categorical interpretation)

21 EUCAST table abbreviations NA Not Applicable (used for screening tests when they are not applicable to particular organisms) IP In preparation (breakpoints will be established)

22 EUCAST breakpoint table links to rationale documents Click on antibiotic for Rationale Document

23 EUCAST breakpoint table links to MIC distributions Click on MIC breakpoint for MIC distributions

24 EUCAST breakpoint table links to zone diameter distributions Click on zone breakpoint for zone diameter distributions

25 EUCAST website (

26 EUCAST MIC and zone diameter distributions website

27 EUCAST MIC and zone distributions Select MIC or zone Select agent or diameter distribution species

28 EUCAST MIC and zone distributions Blue indicates wild type Clinical breakpoints and ECOFF Link to graph

29 EUCAST MIC distributions Do not infer resistance rates May include truncated distributions

30 EUCAST MIC distributions Insufficient data to define ECOFF

31 EUCAST zone diameter distributions

32 EUCAST MIC-zone diameter correlation

33 Summary EUCAST provides clinical breakpoints, non-species-related breakpoints and epidemiological cut-off values (ECOFF) Be aware of formatting conventions and abbreviations in EUCAST breakpoint tables and on EUCAST MIC and zone diameter distributions website