Incidence and risk factors for musculoskeletal adverse effects associated with daptomycin in patients receiving outpatient parenteral antimicrobial therapy.

Background: Daptomycin is preferred in outpatient parenteral antimicrobial therapy (OPAT) due to daily dosing. Elevations in creatine phosphokinase (CPK) of 3%-10% and musculoskeletal adverse events have been described with daptomycin, but data regarding risk factors and frequency of monitoring in the OPAT setting is limited. We evaluated the incidence and risk factors for CPK elevation and musculoskeletal adverse effects in patients receiving daptomycin OPAT. Methods: This was a single-center, retrospective cohort study of adults on OPAT with daptomycin and at least two CPK values. The primary outcome was the incidence of CPK values greater than 500 U/L. Results: We included 127 patients. Most patients were male (55.1%), and the median age was 56 years (IQR 46-63). The most common indication was bone/joint infections (73.2%, n = 93). The median daptomycin dose was 7.4 mg/kg/day (IQR 6.1-8.1) and duration of therapy was 37 days (IQR 21-44). Fifteen patients (11.8%) experienced a CPK greater than 500 U/L within a median 13 days (IQR 9-16). Five patients (3.9%) developed rhabdomyolysis. Independent predictors of CPK>500 U/L included male sex (OR, 4.2 [95% CI, 1.05-16.61]; Conclusions: The incidence of CPK elevation was similar previously reported rates. This expands the literature to patients with daptomycin doses>6 mg/kg and prolonged durations of therapy. The incidence of CPK elevation and time to onset of 9-16 days supports the current recommendations for weekly lab monitoring.