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Randomized Controlled Trial
. 2008 Dec;62(6):1413-21.
doi: 10.1093/jac/dkn372. Epub 2008 Sep 8.

Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates

Susan J Rehm  1 , Helen Boucher, Donald Levine, Marilyn Campion, Barry I Eisenstein, Gloria A Vigliani, G Ralph Corey, Elias Abrutyn
Affiliations
Randomized Controlled Trial

Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates

Susan J Rehm et al. J Antimicrob Chemother. 2008 Dec.

Abstract

Objectives: In a prospective, randomized trial, daptomycin was non-inferior to standard therapy for Staphylococcus aureus bacteraemia and right-sided endocarditis. Since rates of infection due to methicillin-resistant S. aureus (MRSA) infection are increasing and treatment outcomes for bacteraemia caused by MRSA are generally worse than those observed with methicillin-susceptible S. aureus bacteraemia, clinical characteristics and treatment results in the trial's pre-specified subset of patients with MRSA were analysed.

Methods: Clinical characteristics and outcomes of patients receiving daptomycin were compared with those receiving vancomycin plus low-dose gentamicin. Success was defined as clinical improvement with clearance of bacteraemia among patients who completed adequate therapy, received no potentially effective non-study antibiotics and had negative blood cultures 6 weeks after end of therapy.

Results: Twenty of the 45 (44.4%) daptomycin patients and 14 of the 43 (32.6%) vancomycin/gentamicin patients were successfully treated (difference 11.9%; confidence interval -8.3 to 32.1). Success rates for daptomycin versus vancomycin/gentamicin were 45% versus 27% in complicated bacteraemia, 60% versus 45% in uncomplicated bacteraemia and 50% versus 50% in right-sided MRSA endocarditis. Cure rates in patients with septic emboli and in patients who received pre-enrolment vancomycin were similar between treatment groups. However, in both treatment groups, success rates were lower in the elderly (>/=75 years). Persisting or relapsing bacteraemia occurred in 27% of daptomycin and 21% of vancomycin/gentamicin patients; among these patients, MICs of >/=2 mg/L occurred in five daptomycin and four vancomycin/gentamicin patients. The clinical course of several patients may have been influenced by lack of surgical intervention.

Conclusions: Daptomycin was an effective alternative to vancomycin/gentamicin for MRSA bacteraemia or right-sided endocarditis.

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Figures

Figure 1
Figure 1
The Kaplan–Meier plot of overall survival. Wilcoxon P= 0.25, log-rank P = 0.42.
Figure 2
Figure 2
Effect of prior vancomycin treatment.
Figure 3
Figure 3
Mean serum creatinine. *P ≤ 0.05 compared with daptomycin for change from baseline. Bars represent the standard error of the means.
See this image and copyright information in PMC

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