Early high-dose daptomycin for methicillin-resistant Staphylococcus aureus bloodstream infections with elevated vancomycin minimum inhibitory concentrations: ready for prime time?

Abstract

In this issue of Clinical Infectious Diseases, Murray and colleagues present results from a matched cohort study addressing the clinical conundrum of methicillinresistant Staphylococcus aureus (MRSA) bloodstream infections caused by organisms with elevated vancomycin minimum inhibitory concentrations (MICs) [1]. The investigators conclude that highdose daptomycin treatment led to better outcomes, and they advocate for an early switch from vancomycin to daptomycin based on finding a vancomycin MIC >1 μg/mL. Although the study provides new insight into this important clinical problem, several key questions remain. A growing body of data shows that S. aureus isolates with higher vancomycin MICs are associated with a significant increase in the risk of worse clinical outcomes, including treatment failure and death [2, 3]. It is unknown whether these poor outcomes represent relative resistance to vancomycin, a marker for a more virulent organism, or some undefined third factor associated with worse outcomes. Holmes et al found that the association between higher vancomycin MICs and clinical failure persisted even in patients with methicillin-susceptible S. aureus treated with β-lactam therapy [4]. This makes the decision regarding treatment of patients with MRSA bloodstream infection with an elevated vancomycin MIC even less clear. Should they be switched to an alternative therapy early, based on MIC testing, or wait until they develop persistent bloodstream infection or other signs of clinical failure? Current guidelines from the Infectious Diseases Society of America recommend higher doses of vancomycin based largely on pharmacokinetic and pharmacodynamic data and suggest that “if the patient has not had a clinical or microbiologic response to vancomycin despite adequate debridement and removal of other foci of infection, an alternative to vancomycin is recommended regardless of MIC.” The experts acknowledge that a paucity of clinical trial data supports this recommendation [5]. Moore et al showed that patients switched to daptomycin after clinically failing vancomycin had improved mortality, but until now no one has investigated the early use of an alternative [6]. In this current study, Murray et al conducted a retrospective cohort study of patients with MRSA bloodstream infection who were switched to daptomycin early (after an average 1.7 days of therapy) on the basis of detection of a vancomycin MIC of >1 and ≤2 μg/L [1]. This limits the problem of bias-by-indication seen in prior studies, as no other factors played a role in the decision to switch. Their cohorts were well matched and represented a relatively ill population with an average Pitt bacteremia score of 2. Vancomycin levels were relatively high with a mean trough of 18.1 μg/mL, well within the recommended range, though few, about 10%, reached target exposures [1]. The investigators further attempted to avoid bias by defining bacteremia from the start of any MRSA therapy; they “counted” the duration of prior vancomycin therapy where applicable. We applaud these efforts to limit confounding that has been present in prior trials. In the primary analysis, Received 14 February 2013; accepted 19 February 2013; electronically published 28 February 2013. Correspondence: Helen W. Boucher, MD, FIDSA, FACP, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, 800 Washington St, Box 238, Boston, MA 02111 (hboucher@tuftsmedicalcenter.org). Clinical Infectious Diseases 2013;56(11):1570–2 © The Author 2013. 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/cit118

DOI: 10.1093/cid/cit118

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@article{Weston2013EarlyHD, title={Early high-dose daptomycin for methicillin-resistant Staphylococcus aureus bloodstream infections with elevated vancomycin minimum inhibitory concentrations: ready for prime time?}, author={Adam R W Weston and Helen W. Boucher}, journal={Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, year={2013}, volume={56 11}, pages={1570-2} }