Vancomycin MICs (V-MIC) and the frequency of heteroresistant vancomycin-intermediateisolates with V-MICs of <1, 1.5, 2, and 3 g/ml, respectively (P < 0.001). The V-MIC distribution and the hVISA frequency were stable over the 11-year period. Most patients (89.0%) received vancomycin. The mortality rate (evaluated with 285 patients for whose isolates the trough V-MIC was >10 g/ml) was comparable for patients whose isolates had V-MICs of <1 and 1.5 g/ml (19.4% and 27.0%, respectively; P ؍ 0.2) but higher for patients whose isolates had V-MICs of >2 g/ml (47.6%; P ؍ 0.03). However, the impact of V-MIC and hVISA status on mortality or persistent (>7 days) bacteremia was not substantiated by multivariate analysis. Staphylococcal chromosome cassette mec (SCCmec) typing of 261 isolates (including all hVISA isolates) revealed that 93.0% of the hVISA isolates were SCCmec type II. These findings demonstrate that the V-MIC distribution and hVISA frequencies were stable over an 11-year span. A V-MIC of >2 g/ml was associated with a higher rate of mortality by univariate analysis, but the relevance of the V-MIC and the presence of hVISA remain uncertain. A multicenter prospective randomized study by the use of standardized methods is needed to evaluate the relevance of hVISA and determine the optimal treatment of patients whose isolates have V-MICs of >2.0 g/ml.
No adverse outcome was documented with hVISA phenotype, whereas VISA contributed to vancomycin treatment failure. VISA and hVISA appear to emerge in SCCmec II isolates among vancomycin-exposed patients and are better detected by Etest.
Methicillin-resistant Staphylococcus aureus (MRSA) vancomycin minimum inhibitory concentrations (V-MICs) are sometimes reported to be higher according to Etest versus broth microdilution (BMD). These observations are often interpreted as an Etest overestimation of the actual MIC. We measured V-MIC of 484 MRSA blood isolates using Etest, BMD, and a modified BMD (M-BMD) with incremental dilutions parallel to the Etest scale, correlated the results with population analysis profile-area under the curve (PAP-AUC). All MIC tests were done in parallel. The mean V-MIC was comparable (1.83 ± 0.44 [Etest], 1.88 ± 0.67 [BMD] and 1.75 ± 0.57 mg/L [M-BMD]; p = 0.9 [ANOVA]). The V-MICs/PAP-AUC correlation coefficient was 0.555 (Etest), 0.513 (BMD), and 0.586 (M-BMD). Etest MICs were equal (44.2 %), one dilution higher (21.9 %), two dilutions higher (2.5 %), one dilution lower (29.8 %), and two dilutions lower (1.6 %) than BMD MICs and were equal (61.5 %), one dilution higher (28.3 %), two dilutions higher (0.4 %), one dilution lower (9.5 %), and two dilutions lower (0.2 %) than M-BMD MICs. The mean PAP-AUC for Etest vs M-BMD among isolates with similar Etest/M-BMD MIC values was 0.25 ± 0.15 vs 0.35 ± 0.13 (p = 0.8), 0.46 ± 0.16 vs 0.50 ± 0.17 (p = 0.8), 0.64 ± 0.19 vs 0.67 ± 0.21 (p = 0.9), and 0.90 ± 0.31 vs 0.88 ± 0.25 (p = 1.0) for isolates with V-MIC of ≤ 1, 1.5, 2, and ≥ 3 mg/L respectively. These results suggest that Etest might not overestimate V-MIC in comparison to M-BMD or BMD; Etest and M-BMD tests depict comparable PAP-AUC and have a higher correlation with PAP-AUC than the conventional BMD, probably because of the more detailed results. Etest may be more suitable than conventional BMD for MIC outcome assessment because of the more detailed MICs.
We agree that the use of rapid ATP testing has a growing body of published support. However, the lack of common acceptance for rapid ATP testing at this point in time is well expressed in the EPIC 3 Guidelines (2014) from an expert committee in the United Kingdom. 2 Unfortunately, Ms Roady somewhat misses the point of our paper. In our study, we did not attempt to equate rapid ATP testing with detection of bacterial contamination. We showed that the variability that occurs when measuring responses to controlled quantitated microbial cultures is the same variability that occurs when controlled concentrations of pure ATP solutions are measured. The issue is therefore not correlation with detection but data variability.This variability is undetectable to ATP device users and applies to all sources of detected ATP. The ATP variability problem (ie, imprecision in results) that we have outlined in our most recent paper is common to each of the ATP device brands we tested. This finding does have implications for sampling methodology and analysis. 3 We set out to validate several branded ATP devices using a standardized approach and focusing on precision and accuracy. 4 The first issue we encountered was uncontrolled variability and the lack of precision at any testing point. The issue of accuracy is problematic because the scale of relative light units (RLU) is neither universally standardized nor standardized among ATP device suppliers.We welcome the engagement with the industry. We would like to see better quality of results for ATP testing devices, including testing for precision and the development of a common measurement scale. There remains a tremendous upside for ATP use once these issues are resolved.
acknowledgmentsPotential conflicts of interest. None of the authors has any conflict of interest to declare.
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