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High‐Dose Daptomycin for Treatment of Complicated Gram‐Positive Infections: A Large, Multicenter, Retrospective Study
Author(s) -
Kullar Ravina,
Davis Susan L.,
Levine Donald P.,
Zhao Jing J.,
Crank Christopher W.,
Segreti John,
Sakoulas George,
Cosgrove Sara E.,
Rybak Michael J.
Publication year - 2011
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.31.6.527
Subject(s) - daptomycin , medicine , interquartile range , bacteremia , retrospective cohort study , endocarditis , methicillin resistant staphylococcus aureus , vancomycin , infective endocarditis , surgery , staphylococcus aureus , antibiotics , microbiology and biotechnology , biology , bacteria , genetics
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.