Evaluation of Vancomycin Susceptibility Testing for Methicillin-Resistant Staphylococcus aureus: Comparison of Etest and Three Automated Testing Methods

Abstract

We evaluated the ability of four commercial MIC testing systems (MicroScan, Vitek 2, Phoenix, and Etest) to detect vancomycin MIC values of <1 to >2 in 200 methicillin-resistant Staphylococcus aureus (MRSA) strains compared to the Clinical and Laboratory Standards Institute broth microdilution (BMD) reference methods. Compared to the BMD method, absolute agreement (0 ؎ dilution) was highest for the Phoenix system (66.2%) and the MicroScan turbidity method (61.8%), followed by the Vitek 2 system (54.3%). The Etest produced MIC values 1 to 2 dilutions higher than those produced by the BMD method (36.7% agreement). Of interest, the MicroScan system (prompt method) was more likely to overcall an MIC value of 1 mg/liter (74.1%), whereas the Phoenix (76%) and Vitek 2 (20%) systems had a tendency to undercall an MIC of 2 mg/liter. The ability to correctly identify vancomycin MIC values of 1 and 2 has clinical implications and requires further evaluation.T he overall prevalence of methicillin-resistant Staphylococcus aureus (MRSA) continues to increase, with vancomycin (VAN) remaining the mainstay of therapy for serious infections (1-3). Over the last several years, there have been a number of studies that have demonstrated an association between vancomycin MICs of 1.5 or 2 mg/liter and failure of vancomycin therapy, even though these values lie within the Clinical and Laboratory Standards Institute's (CLSI's) and the FDA's acceptable vancomycin susceptibility range (Յ2 mg/liter). The majority of these reports were derived from patients with MRSA-complicated bacteremia in whom a vancomycin MIC of 1.5 or 2 mg/liter was associated with persistent signs and symptoms of infection, including prolonged days of bacteremia, increased complications, increased lengths of hospital stay, and mortality (4-9). A recent observational study of 532 patients with MRSA and methicillinsusceptible Staphylococcus aureus (MSSA) bacteremia noted a significantly higher 30-day mortality rate associated with patients who had an isolate for which the MIC exceeded 1.5 mg/liter (by Etest methods). Of interest, this association did not seem to be related to vancomycin treatment, since patients who had MSSA bacteremia with an elevated vancomycin MIC and were treated with flucloxacillin had worse clinical outcomes than flucloxacillin-treated patients with MSSA bacteremia that had a lower vancomycin MIC value (P ϭ 0.012) (10). In addition, a recent systematic review and meta-analysis of the literature regarding the relationship of vancomycin susceptibility and patient outcome concluded that vancomycin MIC values of 1.5 or 2 mg/liter were associated with greater treatment failure and mortality rates in patients with MRSA infections (11). Patients who have serious high-inoculum infections (i.e., infective endocarditis, medical device infections, etc.) with MRSA and for which the strain has been identified as heteroresistant vancomycin-intermediate S. aureus (hVISA) are also more likely to experience prolonged days of bacteremia, increased complications, m...

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

“…The gold-standard broth microdilution (BMD) method is out with the capacity for routine diagnostic use, thus commercial vancomycin MIC detection methods are used in most clinical diagnostic laboratories for susceptibility testing. Previously, investigations evaluating the precision of automated testing methods have used AE1 log 2 dilution from the reference method as having essential agreement [8]. However, with a recent systematic review and meta-analysis showing greater failure rates and mortality with MICs of 1.5 mg/L or 2 mg/L (i.e.…”

“…Recent reports describe discrepancies in the ability of automated systems to accurately determine the MIC of vancomycin against MRSA compared with Etest or reference BMD methods [8,24]. A recent study comparing four commercial MIC testing systems (MicroScan, VITEK 1 2, Phoenix and Etest) against the Clinical and Laboratory Standards Institute (CSLI) reference BMD method showed 61.8%, 54.3%, 66.2% and 36.7% absolute agreement (0 AE dilution) with the BMD method, respectively [8].…”

“…A recent study comparing four commercial MIC testing systems (MicroScan, VITEK 1 2, Phoenix and Etest) against the Clinical and Laboratory Standards Institute (CSLI) reference BMD method showed 61.8%, 54.3%, 66.2% and 36.7% absolute agreement (0 AE dilution) with the BMD method, respectively [8]. Aside from the precision in determination of MICs, this study also highlights the risk of missing vancomycin MICs of 2 mg/L with certain automated systems by undercalling resistance, especially when heteroresistant vancomycin-intermediate S. aureus (hVISA) is involved [8]. Undercalling of resistance occurs both with the VITEK 1 2 and Phoenix systems, although the reason for discrepancies in accuracy between these systems is poorly understood, and given that these types of system are in widespread use it urges for caution in interpretation of susceptibility if infection is severe.…”

“…Undercalling of resistance occurs both with the VITEK 1 2 and Phoenix systems, although the reason for discrepancies in accuracy between these systems is poorly understood, and given that these types of system are in widespread use it urges for caution in interpretation of susceptibility if infection is severe. Etest MIC determination, however, is often known to produce values that are 1 dilution higher than BMD, and this may prove a useful conservative estimate in evaluating vancomycin MICs when treating serious MRSA infections [8,25,26]. The practical difficulties in determining an MIC have led some to argue in favour of lowering the breakpoint as a pragmatic solution.…”

“…A growing body of data showing significant variability both in minimum inhibitory concentration (MIC) measurements and accuracy of MIC determination demonstrates the importance of the method of susceptibility testing [8,9].…”