Comparative Effectiveness of Vancomycin Versus Daptomycin for MRSA Bacteremia With Vancomycin MIC >1 mg/L: A Multicenter Evaluation.

PURPOSE: Clinical studies comparing vancomycin with alternative therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia are limited. The objective of this study was to compare outcomes of early daptomycin versus vancomycin treatment for MRSA bacteremia with high vancomycin MICs in a geographically diverse multicenter evaluation. METHODS: This nationwide, retrospective, multicenter (N = 11), matched, cohort study compared outcomes of early daptomycin with vancomycin for MRSA bloodstream infection (BSI) with vancomycin MICs 1.5 to 2 µg/mL. Matching variables, based on propensity regression analysis, included age, intensive care unit (ICU), and type of BSI. Outcomes were as follows: (1) composite failure (60-day all-cause mortality, 7-day clinical or microbiologic failure, 30-day BSI relapse, or end-of-treatment failure (EOT; discontinue/change daptomycin or vancomycin because of treatment failure or adverse event]); (2) nephrotoxicity; and (2) day 4 BSI clearance. FINDINGS: A total of 170 patients were included. The median (interquartile range) age was 60 years (50-74); the median (range) Acute Physiology and Chronic Health Evaluation II score was 15 (10-18); 31% were in an ICU; and 92% had an infectious disease consultation. BSI types included endocarditis/endovascular (39%), extravascular (55%), and central catheter (6%). The median daptomycin dose was 6 mg/kg, and the vancomycin trough level was 17 mg/L. Overall composite failure was 35% (59 of 170): 15% due to 60-day all-cause mortality, 14% for lack of clinical or microbiologic response by 7 days, and 17% due to failure at end of therapy (discontinue/change because of treatment failure or adverse event). Predictors of composite failure according to multivariate analysis were age >60 years (odds ratio, 3.7; P < 0.01) and ICU stay (odds ratio, 2.64; P = 0.03). Notable differences between treatment groups were seen with: (1) end of therapy failure rates (11% vs 24% for daptomycin vs vancomycin; P = 0.025); (2) acute kidney injury rates (9% vs 23% for daptomycin vs vancomycin; P = 0.043); and (3) day 4 bacteremia clearance rates for immunocompromised patients (n = 26) (94% vs 56% for daptomycin vs vancomycin; P = 0.035). IMPLICATIONS: Results from this multicenter study provide, for the first time, a geographically diverse evaluation of daptomycin versus vancomycin for patients with vancomycin-susceptible MRSA bacteremia with vancomycin MIC values >1 µg/mL. Although the overall composite failure rates did not differ between the vancomycin and daptomycin groups when intensively matched according to risks for failure, the rates of acute kidney injury were significantly lower in the daptomycin group. These findings suggest that daptomycin is a useful therapy for clinicians treating patients who have MRSA bacteremia. Prospective, randomized trials should be conducted to better assess the potential significance of elevated vancomycin MIC.

Retrospective observational study comparing vancomycin versus daptomycin as initial therapy for Staphylococcus aureus infections.

BACKGROUND: Data comparing alternatives to vancomycin for the treatment of Staphylococcus aureus infections with vancomycin MIC >1 are lacking. OBJECTIVE: We evaluated outcomes of S aureus infections based on whether daptomycin or vancomycin was used as initial therapy at a single institution, where the majority of S aureus infections had vancomycin MICs of 2 mg/L. METHODS: A retrospective chart review was conducted at a 450-bed private acute care hospital. All patients >18 years of age who received initial vancomycin or daptomycin for at least 3 days to treat an S aureus infection between November 2006 and July 2008 were included. Patients with endocarditis, osteomyelitis, or a central nervous system infection and/or those being treated for an S aureus respiratory tract infection were excluded. RESULTS: A total of 165 patients (median age 68 years, range 24-95 years; 56% male) were included: 57 (35%) received daptomycin and 108 (65%) received vancomycin; 78% had vancomycin MIC values of 2 mg/L. The median antibiotic-related length of stay was significantly shorter with daptomycin than with vancomycin (7.5 vs 10.0 days; P = 0.035). Relapse rates in the clinically evaluable population were 25% and 23% for daptomycin and vancomycin, respectively; for the subset with S aureus bacteremia with vancomycin MICs of 2 mg/L, rates were 0% (0/9 patients) and 26% (6/23 patients) for daptomycin and vancomycin, respectively (P = 0.089). Thirty-day all-cause mortality was 6% (10/165 patients) and did not differ significantly by treatment: 7% (4/57 patients) versus 6% (6/108 patients) for daptomycin and vancomycin, respectively (P = 0.708). CONCLUSION: In this setting, in which the majority of S aureus infections had vancomycin MIC values of 2 mg/L, we found the median antibiotic-related length of stay to be significantly shorter with daptomycin than with vancomycin. Prospective studies are needed to determine whether daptomycin confers benefits over vancomycin in specific infection types under conditions that are unfavorable for vancomycin, such as higher vancomycin MICs.