Susceptibility testing for Vancomycin in S. aureus : What do we do now?

1. Antimicrobial use in Primary Care Susceptibility testing for Vancomycin in S. aureus: What do we do now? 14th March 2013 Robin A Howe

2. Susceptibility testing for Vancomycin in S. aureus: What do we do now? • History • What are we aiming to identify? • Testing issues • Current recommendations

3. 1997: VISA • Mu50 Vanc MIC 8mg/L • 2001: SARV (S. aureuswith Reduced susceptibility to Vancomycin) • MIC 4mg/L • Associated with mortality in Case-control study • 2003: VRSA • High-level resistance (>32mg/L) due to acquisition of vanA • Remains v rare Hiramatsu et al. (1997) JAC 40: 135 Fridkinet al. 41st ICAAC (2001)

4. 1997: hetero-VISA • Mu3 Vanc MIC 2-4mg/L but population able to grow in higher vanc concentrations • Numerous case reports associating hVISA with treatment failure (lack of systematic studies) Hiramatsu et al (1997) Lancet 350: 1670

5. Is there an association between high MICs below BP and poor outcome? • Meta-analysis • high-VMIC • VMIC >1 mg/L but ≤2 mg/L) • 33 studies identified Mortality Mavros et al. (2012) IJAA. 40: 496

6. Is there an association between high MICs below BP and poor outcome? • Meta-analysis • high-VMIC • ≥1 mg/l by BMD • ≥1.5 mg/l by Etest • 20 studies identified Treatment failure Jacob et al. (2013) IJID. 17: e93

7. What should we aim to identify? • Vanc MIC >2mg/L (ie BP) • ?Vanc MIC ≥1.5mg/L • Caution about method • ?hVISA • PAP analysis can help to define resistance Wootton et al (2005) AAC 49(9): 3982

8. What should we aim to identify? • Vanc MIC >2mg/L (ie BP) • ?Vanc MIC ≥1.5mg/L • Caution about method • ?hVISA • PAP analysis can help to define resistance Wootton et al (2005) AAC 49(9): 3982

9. Disc testing Pennsylvania VRSA (vanA +ve) MIC 32 mg/L Tenover et al. AAC (2004) 48: 275.

10. Disc testing 14 VSSA 49 hVISA 20 VISA tested by disc Davies LE et al. ICAAC (2009). D803.

11. MIC testing • “Gold Standard”: • Microbroth dilution MIC • ISO 20776 • MH broth • Ease of use standard: • Gradient strips • (Etest, MICE, MICtest)

12. Replicate testing (x15) of QC strains by MICE & Etest gradient strips CLSI QC Range: 0.5 – 2 mg/L Richards J et al. ECCMID (2012). P1652.

13. 8 VISA, 59 VSSA(MRSA) • MIC determination by • Etest (BioMerieux) • MICE (Oxoid) • MIC test (Liofilchem/Launch diagnostics) • ISO MBD. Richards J et al. ECCMID (2012). P1652.

14. “Etest tends to give slightly higher MICs” • 182 pts with SAB • Related vancomycin AUC/MIC to outcome (target >400) • Median AUC/MIC • MBD – 436.1 • Etest - 271.5 • CART analysis • AUC/MIC (MBD) >373 assoc with ↓mortality Holmes et al AAC (2013) epub.doi:10.1128/AAC.01485-12

15. Commercial systems • Vitek2 undercalls resistance • Phoenix overcalls resistance Swenson et al. (2009) JCM 47: 2013

16. Screening tests • Screening agars • BHI/MHA • V/T – 4/5/6 • MHA5T best • MacroEtest (2 McF) • Good performance • GRD Etest (0.5 McF) • Good performance Walsh et al (2001) JCM 39: 2439 Wootton et al (2007) JCM 45: 329 Wootton et al (2008) ICAAC D2214

17. Conclusions • Aim to identify MIC >2mg/L • Closeness of BP to MICs of wild population challenges all methods • Disc testing not reliable • MIC methods require close attention to QC/QA • Automated systems struggle • Population analysis can confirm reduced susceptibility • Screening methods may have a role but lack sensitivity

18. Current recommendations • Do not use disc testing • Use MIC method • BMD gold standard • Control all tests with QC strains (monitor QC results for trends even within appropriate QC range) • Consider targeted testing

19. Acknowledgements Dr Mandy Wootton Leanne Davies Jennifer Richards Prof Tim Walsh Jenny Andrews BSAC AST Working Group