A Pharmacovigilance Analysis of Daptomycin Use Based on CLSI Susceptible Dose-Dependent Category

Abstract Introduction Daptomycin doses 8–12 mg/kg are recommended for susceptible dose-dependent Enterococcus species. However, data remain limited on safety outcomes of such dosing, compared to standard 4–6 mg/kg dosing. Methods In this retrospective cohort study, patients were stratified into dapt...

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Bibliographic Details
Main Authors: Ming M. Zhang, Ryan W. Stevens, Jennifer L. Adema, Kristin C. Mara, Audrey N. Schuetz, Aaron J. Tande, Christina G. Rivera
Format: Article
Language:English
Published: Adis, Springer Healthcare 2023-09-01
Series:Infectious Diseases and Therapy
Subjects:
Online Access:https://doi.org/10.1007/s40121-023-00868-0
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Summary:Abstract Introduction Daptomycin doses 8–12 mg/kg are recommended for susceptible dose-dependent Enterococcus species. However, data remain limited on safety outcomes of such dosing, compared to standard 4–6 mg/kg dosing. Methods In this retrospective cohort study, patients were stratified into daptomycin standard-dose (≤ 6.5 mg/kg) versus high-dose (≥ 7.5 mg/kg) groups. The primary outcome was daptomycin safety based on a composite of creatine kinase elevation, daptomycin-related peripheral blood eosinophilia, eosinophilic pneumonitis, alanine aminotransferase elevation, and alkaline phosphatase elevation. A secondary aim was to identify risk factors for daptomycin adverse effects. Inclusion criteria were age ≥ 18 years old, daptomycin receipt for ≥ 48 h, and Enterococcus cultures with a daptomycin minimal inhibitory concentration 2–4 mg/L. Results A total of 119 patients were included for analysis. Median daptomycin doses were 6.0 mg/kg (IQR 5.4, 6.1) and 8.1 mg/kg (IQR 7.9, 9.6) in the standard- and high-dose cohorts, respectively. Median durations were 13.5 days (standard-dose) and 16 days (high-dose) (p = 0.02). The composite safety endpoint occurred in 32.0% of the standard-dose group and 32.5% of the high-dose group (p = 0.96). Daptomycin was dose-reduced or held in 8.1% of patients experiencing an adverse effect. Concurrent antihistamine usage was associated with the composite outcome; however, there was no association with daptomycin dose or concurrent statin use. Conclusion High-dose daptomycin was not associated with increased laboratory abnormalities or adverse drug reactions compared to standard-dose daptomycin.
ISSN:2193-8229
2193-6382