Journal
PHARMACOTHERAPY
Volume 33, Issue 12, Pages 1322-1330Publisher
WILEY-BLACKWELL
DOI: 10.1002/phar.1298
Keywords
obesity; daptomycin; Staphylococcus aureus; morbid obesity; creatine phosphokinase; HMG Co-A reductase
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Funding
- Cubist Pharmaceuticals
- Merck Co., Inc.
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STUDY OBJECTIVE Data are limited for antimicrobial outcomes in obese patients. This study investigated the safety and clinical outcomes of daptomycin therapy in a hospitalized obese population in the southeastern United States. DESIGN Multicenter retrospective cohort study. SETTING Thirteen hospitals in the southeastern United States. PATIENTS A total of 126 hospitalized adult obese patients (body mass index [BMI] more than 30 kg/m(2)) admitted from January 2005 through May 2010 who received daptomycin dosed on actual body weight for any indication for a minimum of 7 days. MEASUREMENTS AND MAIN RESULTS Primary safety outcomes included incidence of creatine phosphokinase (CPK) elevations more than 1000 units/L, more than 500 units/L, myalgias, and discontinuation of therapy due to adverse drug events (ADEs). Patients were stratified by BMI class (I, II, or III) for analyses. The average weight was 121 kg, and 39% of patients were considered morbidly obese. Factors associated with an increased risk of primary safety outcomes were assessed through regression analysis. Clinical effectiveness was evaluated as a secondary outcome. CPK elevations more than 1000 units/L occurred in 8.4% of evaluable patients and specifically in 1 (3.6%), 3 (10.3%), and 4 (10.5%) patients in BMI class I, II, and III, respectively (p=0.554). CPK elevations more than 500 units/L occurred in 13.7% of patients with no statistically significant difference noted across BMI classes. Discontinuation due to ADEs occurred in 8 patients (6.3%). One patient developed rhabdomyolysis on day 9 of therapy. Clinical effectiveness was documented in 71% of patients and was consistent across BMI classes. CONCLUSION Although elevations in CPK increased in high-risk obese patients on daptomycin, discontinuation rates due to ADEs remained low. Further evaluation in a prospective trial is warranted.
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