Daptomycin Demonstrates Potential in MRSA Bloodstream Infections
SAN FRANCISCO, CA—Daptomycin may be a feasible treatment option for patients with Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection when vancomycin MICs are 1.5–2.0 μg/mL, as reported at IDWeek 2013.
Evidence from single center studies suggest that daptomycin may provide a clinical advantage over vancomycin for MRSA bloodstream infections when vancomycin MICs are >1 μg/mL. However multicenter studies examining the efficacy of daptomycin for the treatment of MRSA bloodstream infections have been limited.
In a multicenter, retrospective study, Pamela A. Moise, PharmD from Cubist Pharmaceuticals, Lexington, MA, and colleagues examined clinical and microbiological outcomes of daptomycin, when used as initial or early therapy (≤5 days of prior vancomycin) in MRSA BSI with vancomycin MICS of 1.5–2.0 μg/mL. Investigators also aimed to define matching criteria for comparison of daptomycin and vancomycin for this indication.
Dr. Moise and colleagues utilized electronic case report forms to collect demographic, clinical, and microbiological information. Hospitalized adults >18 years old (n=93) from 11 U.S. institutions were included if they received daptomycin >6mg/kg for at least 3 days for the treatment of MRSA bacteremia, had a positive blood culture for MRSA with a vancomycin MIC of 1.5–2.0 μg/mL, and received initial anti-MRSA therapy within 72 hours of index blood culture collection.
Patients were not included if they had confirmed MRSA BSI in the previous 30 days; prosthetic valve endocarditis, infected cardiac device, MRSA pneumonia, or polymicrobial bacteremia; single tunneled catheter related bacteremia; concomitant daptomycin and vancomycin therapy for >24 hours; or received >5 days of vancomycin prior to daptomycin initiation. Susceptibility data for vancomycin and daptomycin was collected for the first positive and last positive blood culture.
The composite endpoint was composite failure including, 60-day all-cause mortality, 7-day clinical or microbiological failure, 30-day BSI relapse, and failure at end of therapy (discontinued or changed study drug therapy for failure or adverse event). Bacteremia clearance at day 4 and 7 was also assessed.
Fifty four percent of patients received ≤2 days of vancomycin prior to daptomycin therapy and 17% received no prior vancomycin. The median daptomycin dose was 6 mg/kg (range: 6–10g/kg) with a median duration of 16 days (range: 3–142 days).
Overall composite failure was observed in 30% of patients, 18% (n=28) due to 60-day all cause mortality, 10% for lack of MRSA clearance by day 7, and 4% (n=4) switched to alternative for daptomycin failure. No recurrences were noted. The majority of patients (79%) cleared their bacteremia by day 4.
Logistic regression identified 60-day all-cause mortality to be associated with ICU stay (OR, 4.43 [95% CI, 1.39–14.2]; P=0.012) & increased age (OR, 1.04 [95% CI, 1.00–1.07]; P=0.038). No relationship was noted between time to bacteremia clearance (by day 4 and 7, respectively) & 60-day mortality (P=0.204 and P=0.468, respectively).
“MRSA bacteremia is a heterogeneous disease with different rates of response to antimicrobial therapy based on the primary focus of infection,” Dr. Moise noted. Patient mortality was related to severity of illness (ICU stay) and advanced age.