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

J Antimicrob Chemother. 2008 Dec;62(6):1413-21. doi: 10.1093/jac/dkn372. Epub 2008 Sep 8.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Daptomycin / pharmacology
  • Daptomycin / therapeutic use*
  • Endocarditis, Bacterial / drug therapy*
  • Female
  • Gentamicins / pharmacology
  • Gentamicins / therapeutic use*
  • Humans
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / isolation & purification
  • Microbial Sensitivity Tests
  • Middle Aged
  • Prospective Studies
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Treatment Outcome
  • Vancomycin / pharmacology
  • Vancomycin / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Gentamicins
  • Vancomycin
  • Daptomycin