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We are receiving requests to look for heteroresistant subpopulations of S. aureus with reduced susceptibility to vancomycin (hVISA. We use the macro-Etest method with a 2.0 McFarland suspension/200 ul on a BHI plate. If we see colonies growing in the vancomycin inhibition zone at 8 mg/L, the test is positive. But results should be confirmed with population analysis profiles (PAP-AUC ratios) by a reference lab. We are trying to see what % of our S. aureus strains test positive. Are other labs doing this test? If a patient is not doing well on vancomycin it would seem to make sense to switch to another drug, such as daptomycin or linezolid, regardless of whether we can find a vancmycin resistant subpopulation.
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The detection of hVISA is a difficult issue. The definition of hVISA varies a bit, but the most common definition is S. aureus for which the vancomycin MIC is 1-4 ug/ml by broth microdilution and which demonstrate a more vancomycin resistant subpopulation by the population analysis profile-area under the curve method [Wootton, M. et al. 2001. J. Antimicrob. Chemother. 47:399-403].
There are three problems:
1. The population analysis assay is labor-intensive and not practical for the clinical laboratory. I am not aware of a reference laboratory in the United States that will perform this assay.
2. The most practical laboratory test is the macrodilution Etest method that you describe. When compared to population analysis, this assay demonstrated 70% sensitivity and 89% specificity for detection of hVISA [Wootton, M. et al. 2007. J. Clin. Microbiol. 45:329-332].
3. There is little data correlating hVISA as defined by population analysis to clinical outcomes. Therefore, it is not clear that the “gold standard” for detection of hVISA, population analysis, is clinically relevant.
The transition from VSSA to VISA is gradual and it is not clear when and how the laboratory can detect these changes. Clinicians would like the laboratory to detect these gradual changes and give an early prediction of therapeutic failure, but the cellular changes that result in the VISA phenotype are not well understood so it is unlikely that a better laboratory test will be available in the near future. As you mention, if patients with a S. aureus are failing vancomycin therapy, therapeutic changes should be considered regardless of a laboratory test.
We hope that we were able to answer your question.
Please visit us again at the American Society for Microbiology.
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