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In this issue, Moore et al [1] provide the first data investigating the results of using an alternative agent in patients with methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) with elevated vancomycin minimum inhibitory concentrations (MICs). In this retrospective analysis, funded by an InvestigatorInitiated Research Grant from Cubist Pharmaceuticals, investigators in Detroit, MI, attempt to tackle the daunting clinical issue of how to best manage these complex patients. Current Infectious Diseases Society of America (IDSA) guidelines suggest that ‘‘if the patient has not had a clinical or microbiologic response to vancomycindespite adequatedebridement and removal of other foci of infection, an alternative to vancomycin is recommended regardless of MIC’’ [2]. This formal guidance exists despite a paucity of clinical trial data. A growing body of literature suggests that ahigher vancomycinMIC is associated with worse clinical outcomes. While not proven, difficulty in achieving optimal vancomycin exposure, measured via the area under the plasma concentration time curve (AUC)/MIC ratio, provides a plausible explanation [3]. However, data from several studies raise questions about this direct causal association. Holmes et al [4] found the association between higher vancomycin MICs and clinical failure persisted even in patients with methicillin-susceptible S. aureus treated with b-lactam therapy. Recently, Walraven et al [5] published a study that showed that the site of MRSA infection, in their case pneumonia or endocarditis, was predictive of outcome rather than vancomycin MIC. In this study,Moore et al [1] investigate the clinical outcomes of those patients who received daptomycin versus vancomycin in a cohort of patients with baseline vancomycin MICs of 1.5–2 mcg/mL and MRSA BSI. They report a lower incidence of the composite outcome of clinical failure, microbiologic failure, and mortality in daptomycin-treated patients. This result was primarily driven by an absolute 11% difference in mortality; differences in clinical failure and microbiologic failure were not statistically significant. We applaud Moore et al [1] for investigating clinical outcomes of patients who were switched to an alternative agent, as has been suggested by several studies and recent clinical guidelines [2]. Several factors may have influenced the results of the study, including the treatment strategy, actual observedvancomycin levels, use of infectious diseases consultation, potential inadequate vancomycin dosing, and patients’ severity of illness. The very design of this study raises questions about the overall conclusions. The protocol allowed for a switch to daptomycin from another therapy for MRSA; in most cases, vancomycin. In fact, 58/59 patients (98%) who received daptomycin were switched from vancomycin after an average of 5 days of therapy. This introduces selection and indication bias. Multiple reasons, known and unknown, may contribute to changes in therapy for a given patient. Indeed, the groups of patients who were and were not switched might have possessed different characteristics. For example, all of the switched patients had to survive long enough to make the switch. This is reflected in the Kaplan–Meier analysis, which shows survival in the daptomycintreated patients starting at the time of change to daptomycin, not from the time of culture positivity. The authors attempt to minimize selection bias by classifying the reason for the switch, but some bias likely remains even beyond the 38% of patients for whom a reason for the switch Received 23 August 2011; accepted 14 September 2011; electronically published 21 November 2011. Correspondence: Helen W. Boucher, MD, FIDSA, FACP, Director, Infectious Diseases Fellowship Program, Associate Professor of Medicine, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, 800 Washington Street, Box 238 Boston, MA 02111 (hboucher@ tuftsmedicalcenter.org). Clinical Infectious Diseases 2012;54(1):59–61 The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/cir777

clinical infectious diseases/clinical infectious diseases (online. university of chicago. press)

Daptomycin for Methicillin-Resistant Staphylococcus aureus Bloodstream Infection and Elevated Vancomycin Minimum Inhibitory Concentrations: Has the Time Come?