en
Scientific article
English

Daptomycin Exposure as a Risk Factor for Daptomycin-Induced Eosinophilic Pneumonia and Muscular Toxicity

Published inClinical infectious diseases, vol. 77, no. 10, p. 1372-1380
Publication date2023-07-19
First online date2023-07-19
Abstract

Background

High-dose daptomycin is increasingly used in patients with bone and joint infection (BJI). This raises concerns about a higher risk of adverse events (AEs), including daptomycin-induced eosinophilic pneumonia (DIEP) and myotoxicity. We aimed to examine pharmacokinetic and other potential determinants of DIEP and myotoxicity in patients with BJI receiving daptomycin.

Methods

All patients receiving daptomycin for BJI were identified in a prospective cohort study. Cases were matched at a 1:3 ratio, with controls randomly selected from the same cohort. Bayesian estimation of the daptomycin daily area under the concentration-time curve over 24 hours (AUC24h) was performed with the Monolix software based on therapeutic drug monitoring (TDM) data. Demographic and biological data were also collected. Risk factors of AEs were analyzed using Cox proportional hazards model.

Results

From 1130 patients followed over 7 years, 9 with DIEP, 26 with myotoxicity, and 106 controls were included in the final analysis. Daptomycin AUC24h, C-reactive protein, and serum protein levels were associated with the risk of AEs. The adjusted hazard ratio of DIEP or myotoxicity was 3.1 (95% confidence interval [CI], 1.48–6.5; P < .001) for daptomycin AUC24h > 939 mg/h/L, 9.8 (95% CI, 3.94–24.5; P < .001) for C-reactive protein > 21.6 mg/L, and 2.4 (95% CI, 1.02–5.65; P = .04) for serum protein <72 g/L.

Conclusions

We identified common determinants of DIEP and myotoxicity in patients with BJI. Because the risk of AEs was associated with daptomycin exposure, daptomycin TDM and model-informed precision dosing may help optimize the efficacy and safety of daptomycin treatment in this setting. A target AUC24h range of 666 to 939 mg/h/L is suggested.

eng
Keywords
  • Daptomycin
  • Eosinophilic pneumonia
  • Myopathy
  • Pharmacokinetics
  • Therapeutic drug monitoring
Citation (ISO format)
GARREAU, Romain et al. Daptomycin Exposure as a Risk Factor for Daptomycin-Induced Eosinophilic Pneumonia and Muscular Toxicity. In: Clinical infectious diseases, 2023, vol. 77, n° 10, p. 1372–1380. doi: 10.1093/cid/ciad386
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Identifiers
ISSN of the journal1058-4838
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