Recent literature has linked vancomycin treatment failure in patients with serious methicillin-resistant Staphylococcus aureus (MRSA) with higher vancomycin minimum inhibitory concentrations (MICs).1 Current Infectious Diseases Society of America (IDSA) guidelines for the treatment of MRSA infections recommend an alternative treatment regimen for patients failing vancomycin therapy.2 Despite this recommendation, there is limited literature to date to suggest which alternative regimen would have improved clinical outcomes in those patients with MRSA isolates with higher vancomycin MICs.3 Moore and colleagues attempted to address this clinical issue in a recently published study.
The study published by Moore and colleagues, was a retrospective case-control study that evaluated the effectiveness and safety of vancomycin, compared with that of daptomycin, in the treatment of bloodstream infections (BSI) due to MRSA isolates having a high vancomycin MIC.4 The study included adult patients with an index bloodstream MRSA isolate with an MIC or 1.5 or 2 µg/mL, as determined, by E-test methodology, who have received therapy with either vancomycin or daptomycin for ≥ 48 hours. Patients who have switched from other therapies to daptomycin, if daptomycin therapy was started within 14 days of the onset of infection, were also included in this study. The source of BSI was classified into three categories low (associated mortality <10%), intermediate (associated mortality 10-20%) and high risk (associated mortality >20%). The primary end point was clinical failure, which was defined as a composite of 60-day mortality, microbiologic failure, and/or recurrence of MRSA BSI.
A total of 177 patients were enrolled in the study, of whom 59 were cases (the daptomycin-treated group), and 118 were controls (the vancomycin-treated group). The groups were similar with regard to matching criteria, with a mean age of approximately 51 years, a mean APACHE-II score of 14, and similar risk sources (22% low risk, 32% intermediate risk, and 46% high risk). The distribution of vancomycin MICs in the overall study population was 72% for MICs of 1.5 µg/mL and 28% for MICs of 2 µg/mL. Baseline characteristics were similar between groups, with the exception of more chronic kidney disease (6% vs 17%), immunosuppression (13% vs. 27%), osteomyelitis (12% vs. 24%), and isolates with a vancomycin MIC of 2 µg/mL (14% vs. 58%) in the daptomycin group (P < .05 for all comparisons). Of the 59 daptomycin-treated subjects, 58 (98%) were switched to daptomycin from initial therapy (91% were switched from vancomycin).
The composite of clinical failure was lower in daptomycin-treated subjects (31% vs 17%; P = .084), although this did not achieve statistical significance. Mortality (20% vs 9%; P =.046) was significantly lower in daptomycin-treated patients, while microbiologic failure (9% vs 10%; P =.855) and recurrence (6% vs. 3%; P = .620) were similar between groups. A comparison of 60-day mortality between vancomycin and daptomycin-treated patients found a higher probability of survival in the daptomycin-treated group (P = .022).
In this study, the authors report a lower incidence of the composite outcome of clinical failure, microbiologic failure, and mortality in daptomycin-treated patients. There are several factors may have influenced the results and in turn limit the generalizability of these results, including the retrospective study design, the treatment strategy, ...