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.

Clinical Outcomes of Daptomycin for Vancomycin-resistant Enterococcus Bacteremia.

PURPOSE: In light of recent evidence suggesting enhancement of daptomycin activity against vancomycin-resistant Enterococcus (VRE) by ampicillin and other ß-lactam antibiotics, we evaluated the safety profile and clinical efficacy of daptomycin with and without concomitant ß-lactam antimicrobials in the treatment of VRE (faecium or faecalis) bacteremia from multiple centers across the United States. METHODS: Data were collected retrospectively as part of a larger multicenter registry (The Cubicin Outcomes Registry and Experience). Efficacy and clinical outcomes in patients with VRE bacteremia who received at least 3 days of daptomycin with or without concomitant ß-lactams were analyzed. Although all the cases involved daptomycin-susceptible VRE, additional analysis was performed to examine whether the adjunctive ß-lactam would play a more pivotal role in cases where the daptomycin MIC was in the upper limit of the susceptibility range, indicating that daptomycin monotherapy efficacy may be relatively compromised compared with cases with lower daptomycin MICs. FINDINGS: Two hundred sixty-two patients from 33 hospitals were evaluated. Most patients had at least one significant comorbidity, such as solid-organ or bone marrow transplantation (16%), neutropenia (36%), dialysis dependency (20%), or critical illness (36%) requiring care in an intensive care unit. Overall treatment success was 86% (n = 225/262), and treatment success for patients taking concomitant ß-lactams was 86% (n = 105/122). Logistic regression identified treatment failure to be associated with sepsis (odds ratio = 3.42; P = 0.009) and an elevated daptomycin MIC (3-4 µg/mL) (odds ratio = 3.23, P = 0.013). No significant increase in clinical failure was seen among patients with elevated daptomycin MIC who received concomitant ß-lactam therapy (clinical success, 88% vs 79% for MIC ≤2 vs 3-4 µg/mL, respectively; P = 0.417). Of 262 patients, 33 (13%) experienced ≥1 adverse event possibly related to daptomycin (increased creatine kinase in 8 patients). IMPLICATIONS: Overall, daptomycin was effective and well tolerated for VRE bacteremia, with lower effectiveness noted with daptomycin MIC of 3 to 4 µg/mL. Concomitant ß-lactam therapy with daptomycin may improve clinical outcomes in this setting. Further studies are needed to characterize the potential benefit of concomitant ß-lactams with daptomycin.

Recurrent urinary tract infections among women: comparative effectiveness of 5 prevention and management strategies using a Markov chain Monte Carlo model.

BACKGROUND: Recurrent urinary tract infections (UTIs) are a common problem among women. However, comparative effectiveness strategies for managing recurrent UTIs are lacking. METHODS: We performed a systematic literature review of management of women experiencing ≥3 UTIs per year. We then developed a Markov chain Monte Carlo model of recurrent UTI for each management strategy with ≥2 adequate trials published. We simulated a cohort that experienced 3 UTIs/year and a secondary cohort that experienced 8 UTIs/year. Model outcomes were treatment efficacy, patient and payer cost, and health-related quality of life. RESULTS: Five strategies had ≥2 clinical trials published: (1) daily antibiotic (nitrofurantoin) prophylaxis; (2) daily estrogen prophylaxis; (3) daily cranberry prophylaxis; (4) acupuncture prophylaxis; and (5) symptomatic self-treatment. In the 3 UTIs/year model, nitrofurantoin prophylaxis was most effective, reducing the UTI rate to 0.4 UTIs/year, and the most expensive to the payer ($821/year). All other strategies resulted in payer cost savings but were less efficacious. Symptomatic self-treatment was the only strategy that resulted in patient cost savings, and was the most favorable strategy in term of cost per quality-adjusted life-year (QALY) gained. CONCLUSIONS: Daily antibiotic use is the most effective strategy for recurrent UTI prevention compared to daily cranberry pills, daily estrogen therapy, and acupuncture. Cost savings to payers and patients were seen for most regimens, and improvement in QALYs were seen with all. Our findings provide clinically meaningful data to guide the physician-patient partnership in determining a preferred method of prevention for this common clinical problem.