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

Author(s): Rehm SJ, Boucher H, Levine D, Campion M, Eisenstein BI, Vigliani GA, Corey GR, Abrutyn E

Affiliation(s): Cleveland Clinic, Cleveland, OH, USA.

Publication date & source: 2008-12, J Antimicrob Chemother., 62(6):1413-21. Epub 2008 Sep 8.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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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