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Risk factors of daptomycin overexposure: a case-control study.

Clotilde Vellat1,2, Romain Garreau1,2,3, Aurélien Millet4

  • 1Laboratoire de Biométrie et Biologie Evolutive, UMR 5558, CNRS & Université Lyon 1, Villeurbanne, France.

Antimicrobial Agents and Chemotherapy
|November 7, 2025
PubMed
Summary
This summary is machine-generated.

High body mass index (BMI) and irbesartan use increase daptomycin overexposure risk. Renal function impacts daptomycin levels; avoid weight-based dosing in obese patients.

Keywords:
bone joint infectiondaptomycinpharmacokineticstherapeutic drug monitoring

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Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Drug Safety

Background:

  • Therapeutic drug monitoring (TDM) of daptomycin is crucial for optimizing patient outcomes.
  • Unexplained high trough concentrations of daptomycin have been observed, necessitating identification of contributing factors.

Purpose of the Study:

  • To identify risk factors associated with daptomycin overexposure in patients undergoing routine therapeutic drug monitoring.
  • To investigate the influence of patient characteristics and co-administered medications on daptomycin trough concentrations.

Main Methods:

  • A case-control study design was employed, comparing patients with daptomycin trough concentrations (Cmin) ≥60 mg/L (cases) to those with Cmin <60 mg/L (controls).
  • Logistic regression models were used for univariate and multivariate analyses to identify risk factors.
  • Subgroup analyses and pharmacokinetic parameter comparisons were conducted.

Main Results:

  • Increasing body mass index (BMI) (OR 2.9) and co-administration of irbesartan (OR 6.1) were significant risk factors for daptomycin overexposure.
  • Increasing creatinine clearance was associated with a decreased risk of overexposure (OR 0.16).
  • The influence of BMI was linked to non-linear pharmacokinetics and weight-based dosing in obese individuals.

Conclusions:

  • Elevated BMI and concurrent irbesartan use are associated with an increased risk of daptomycin overexposure, beyond renal impairment.
  • Weight-based dosing of daptomycin should be reconsidered in obese patients to prevent overexposure.