Concepts and needs for expert rules and intrepretive reading of the antibiogram The EUCAST perspective

1. Concepts and needs for expert rules and intrepretive reading of the antibiogram The EUCAST perspective Derek Brown Health Protection Agency Addenbrooke’s Hospital, Cambridge

2. What is an expert rule? • Description of action to be taken, based on current evidence, in response to specific antimicrobial susceptibility test results

3. What is interpretive reading? • Inference of resistance mechanisms from susceptibility test results and interpretation of clinical susceptibility on the basis of the resistance mechanism • This is one type of expert rule

4. Types of expert rules • Intrinsic resistance • Exceptional phenotypes (mainly resistance) • Interpretive reading

5. Intrinsic resistance • Inherent (not acquired) resistance which is a characteristic of all or almost all representatives of the species. • Antimicrobial susceptibility testing unnecessary but may be done as part of panels of test agents. • “Susceptible” results should be viewed with caution • errors in identification or susceptibility testing • If susceptibility is confirmed the drug should be used with caution

6. Intrinsic resistance examples • Specific Gram-positive or Gram-negative agents • Enterobacteriaceae and glycopeptides • Enterococci and fusidic acid • Klebsiella sp. and ampicillin • Proteus mirabilis and nitrofurantoin or colistin • Serratia marcescens and colistin

7. Exceptional phenotypes (usually resistance) • Resistance in a species where resistance has not been seen or is rare. • “Resistant” results should be viewed with caution • errors in identification or susceptibility testing • If resistance is confirmed send the isolate to a reference laboratory for independent confirmation • Exceptional resistance phenotypes may change with time • There may also be regional or national differences

8. Exceptional phenotype examples • S. pyogenes resistant to penicillin • S. aureus resistant to vancomycin • E. faecalis resistant to ampicillin • Enterobacteriaceae resistant to carbapenems • Anaerobes resistant to metronidazole • E. faecium susceptible to ampicillin

9. Interpretive reading • Test susceptibility • Infer resistance mechanism • Interpret clinical susceptibility on the basis of the resistance mechanism

10. Interpretive reading examples • may be simple e.g. ……..IF S. aureus is resistant to oxacillin or cefoxitin Resistance mechanism PBP2’ mediated by mecA THEN report resistant to all β-lactams • or more complicated e.g.……IF Enterobacteriaceae intermediate to tobramycin, resistant to gentamicin and susceptible to amikacin • Resistance mechanism ANT(2”) enzyme - may be low expression and isolates may have decreased susceptibility to tobramycin. • THEN report resistant to tobramycin

11. Actions indicated by expert rules • Recommendations on reporting • Inference of susceptibility • Editing of results from S to I or R, from I to R, but NEVER I or R to S • Suppression of results • Addition of comments • Advice on further tests • Advice on referral of isolates

12. Requirements for use of expert rules in clinical laboratories • Identify the organism fully • May need to test an extended range of appropriate antibiotics • Access to a set of expert rules

13. An “expert system” for susceptibility testing? Human experts are rare and are not available in most laboratories……..

14. “Expert systems” for susceptibility testing are computer based programs for application of expert rules • Stand alone programs • Laboratory information systems • Programs linked to susceptibility testing devices and rules applied automatically to susceptibility results

15. EUCAST expert rules • Written description of current expert rules • Comprehensive collection of rules brought together by an expert subcommittee • May be applied manually or incorporated into automated systems

16. Development of EUCAST expert rules • First draft prepared by expert subcommittee • Consultation with EUCAST national breakpoint committees • Second draft for open consultation via EUCAST public website, EUCAST national breakpoint committees, EUCAST national representatives, industry networks and experts • Version 1 published April 2008 • Will need to be updated regularly and validated for EUCAST breakpoints

17. Expert rules should be evidence based • Should be based on current evidence • Evidence should be published • Quality of evidence should be assessed • Exceptions should be noted

18. Grading of evidence base for EUCAST Expert rules A There is clinical evidence that reporting the test result as susceptible leads to clinical failures. B Evidence is weak and based only on a few case reports or on experimental models. It is presumed that reporting the test result as susceptible may lead to clinical failures. C There is currently no clinical evidence, but microbiological data suggest that clinical use of the agent should be discouraged.

19. Presentation of EUCAST expert rulesIntrinsic resistances

20. Presentation of EUCAST expert rulesExceptional phenotypes

21. Presentation of EUCAST expert rulesInterpretive reading rules for specific groups of organisms

22. Expert rules • EUCAST expert rules are an up-to-date and comprehensive collection of accumulated knowledge of intrinsic resistances, exceptional phenotypes and interpretive reading • It is intended that the rules will be applied to routine antimicrobial susceptibility tests and will make a significant contribution to the quality of reported results