High vancomycin minimum inhibitory concentration and clinical outcomes in adults with methicillin-resistant Staphylococcus aureus infections: a meta-analysis

Abstract

SUMMARY Background Patients with methicillin-resistant Staphylococcus aureus (MRSA) infections caused by isolates with a high but ‘susceptible’ minimum inhibitory concentration (MIC) to vancomycin may suffer poor outcomes. The aim of this study was to determine the association of high compared to low vancomycin MICs and clinical outcomes (treatment failure and mortality) in patients with MRSA infections. Methods PubMed, the Cochrane Library, and electronic abstracts from meetings were queried from January 2000 to July 2010. Two reviewers independently screened titles and abstracts of studies evaluating outcomes of patients with MRSA infections, using broth microdilution (BMD) or the Etest to determine MIC, for full-text review. Patients participating in included studies were classified into two mutually exclusive groups: high MIC or low MIC. High MIC was defined as MIC ≥1 mg/l by BMD or ≥ 1.5 mg/l by Etest. Study-defined failure and mortality were assessed in each group. Results Fourteen publications and six electronic abstracts met the inclusion criteria, with 2439 patients (1492 high MIC and 947 low MIC). There was no evidence of publication bias or heterogeneity. An increased risk of failure was observed in the high MIC group compared to the low MIC group (summary risk ratio (RR) 1.40, 95% confidence interval (CI) 1.15–1.71). The overall mortality risk was greater in the high MIC group than in the low MIC group (summary RR 1.42, 95% CI 1.08–1.87). Sensitivity analyses showed similar findings for failure (summary RR 1.37, 95% CI 1.09–1.73) and mortality (summary RR 1.46, 95% CI 1.06–2.01) for patients with bacteremia. The study quality was poor-to-moderate, and study-defined endpoints were variable. Conclusions A susceptible but high MIC to vancomycin is associated with increased mortality and treatment failure among patients with MRSA infections.

Analysis of Staphylococcal Toxins and Clinical Outcomes of Methicillin-Resistant <i>Staphylococcus aureus</i> Bacteremia

“…24) Host factors, pathogen factors, clinical management, and microbiological factors, such as methicillin resistance and VCM MICs, were found to be associated with mortality. [5][6][7]9,24) However, a recent meta-analysis reported no differences in the risk of death in patients with S. aureus high and low VCM MICs. 8) Our previous study showed that there was no significant difference between the survival and dead group in the VCM AUC/MIC.…”

“…Previous meta-analyses have attempted to address the association between MIC and clinical outcomes. [5][6][7] In contrast to these studies, a recent meta-analysis examining 8291 episodes reported no differences in the risk of death between patients with S. aureus high and low VCM MICs. 8) These results highlight the current lack of consensus regarding the relationship between VCM MICs and the prognosis of patients with MRSA infections.…”

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

“…However, these were written in 2010 and evidence has continued to emerge since their inception and subsequent publication. Meta-analyses have consistently shown poorer outcomes with MICs approaching the breakpoint (>1 mg/L), including mainly episodes of bacteraemia but also pneumonia and skin and soft-tissue infections (SSTIs) [12][13][14]. The vancomycin MIC was significantly associated with mortality for MRSA infection irrespective of the source of infection or MIC methodology [odds ratio (OR) = 1.64, 95% confidence interval 1.14-2.37], although this was mostly attributable to bloodstream infections and Etest MICs of 2 mg/L [12].…”

Community-acquired Staphylococcus aureus bacteremia in children: a cohort study for 2010-2014

“…19 A meta-analysis published in 2014 comparing the clinical course of patients with MRSA bacteremia failed to demonstrate an association between a MIC of vancomycin below or above 1.5 µg/L and mortality. 20 In this study, the analysis was not adjusted for severity or delay in definite therapy; however, it is worth noting that all deceased patients were in the MRSA group.…”