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    In: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Wiley, Vol. 31, No. 6 ( 2011-06), p. 527-536
    Abstract: Study Objective. To evaluate the clinical response and safety of high‐dose daptomycin for treatment of complicated gram‐positive infections. Design. Multicenter, retrospective, observational, case series analysis. Setting. Five academic medical centers in four major United States cities. Patients. Two hundred fifty adults, not undergoing dialysis, who received high‐dose daptomycin (≥ 8 mg/kg/day) for at least 72 hours for complicated gram‐positive infections between January 1, 2005, and March 1, 2010. Measurements and Main Results. Clinical and microbiologic outcomes were assessed at the end of high‐dose daptomycin therapy. Safety evaluations were recorded for all patients, and when available, baseline, end‐of‐therapy and highest observed serum creatine phosphokinase (CPK) levels were recorded. Methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant Enterococcusfaecium (VRE) were the primary organisms isolated. The median dose of daptomycin was 8.9 mg/kg/day (interquartile range [IQR] 8.0–10.0 mg/kg/day). The median duration of daptomycin during hospitalization for MRSA and VRE infection was 10 days (IQR 5–16 days) and 13 days (IQR 6–18 days), respectively. Among the 250 patients, high‐dose daptomycin was primarily used as salvage therapy after vancomycin treatment (184 patients [73.6%] ). Primary infections included complicated bacteremia (119 patients [47.6%]), endocarditis (59 [23.6%] ), skin or wound (70 [28.0%]), and bone or joint (67 [26.8%] ). Overall, clinical response and microbiologic success were assessed in 83.6% (209/250 patients) and 80.3% (175/218 patients), respectively. Isolates from 13 patients (5.2%) developed nonsusceptibility to daptomycin, with most of these patients having extended vancomycin exposure. Three patients (1.2%) developed an adverse event attributable to high‐dose daptomycin therapy, with the event considered either mild or moderate in severity. The median end‐of‐therapy CPK level was 39 U/L (IQR 26–67 U/L). No significant correlation was found between daptomycin dose and highest observed CPK level.
    Type of Medium: Online Resource
    ISSN: 0277-0008 , 1875-9114
    Language: English
    Publisher: Wiley
    Publication Date: 2011
    detail.hit.zdb_id: 2061167-5
    detail.hit.zdb_id: 603158-4
    SSG: 15,3
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