Daptomycin versus vancomycin plus gentamicin for treatment of bacteraemia and endocarditis due to Staphylococcus aureus: subset analysis of patients infected with methicillin-resistant isolates.
OBJECTIVE
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.
Rehm
Susan J
SJ
Cleveland Clinic, Cleveland, OH, USA.
Boucher
Helen
H
Levine
Donald
D
Campion
Marilyn
M
Eisenstein
Barry I
BI
Vigliani
Gloria A
GA
Corey
G Ralph
GR
Abrutyn
Elias
E
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy*; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use*; D004697:Endocarditis, Bacterial / Q000188:drug therapy*; D005260:Female; D005839:Gentamicins / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011446:Prospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D014640:Vancomycin; D017576:Daptomycin
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