Impact of Daptomycin Weight-Based Dosing Strategies in Obese Patients with Staphylococcal and Enterococcal Infections Coleton Waggoner, Emily Perez, David Laurent
Background: High-dose daptomycin (>8 mg/kg) is increasingly utilized for severe Staphylococcus aureus and Enterococcus infections. However, optimal weight-based dosing in obese patients remains undefined. Daptomycin exposure is nonlinear with weight, and consequently, obese patients may be at risk for excessive exposure and adverse outcomes when dosing by total body weight (TBW).
Methods: This multicenter retrospective cohort study evaluated hospitalized adult obese patients (BMI ≥30 kg/m²) treated with high-dose daptomycin at ECU Health from January 2022 to July 2025. Patients were categorized into TBW or ABW (adjusted body weight) cohorts as determined by infecting pathogen: 8-10 mg/kg ± 0.5 mg/kg for S. aureus or 10-12 mg/kg + 0.5 mg/kg for Enterococcus spp.
The primary outcome was a composite safety endpoint of serum creatinine kinase (CK) elevation (>600u/L), patient-reported myopathy, rhabdomyolysis, or early discontinuation of daptomycin. Secondary outcomes included individual components of the composite safety endpoints as well as efficacy endpoints including readmission at 90 days, mortality at 90 days, resistance development at 90 days, and daptomycin discontinuation due to lack of efficacy. Baseline characteristics and outcomes were compared between groups using chi-square or Fisher’s exact tests for categorical variables and Mann-Whitney U tests for continuous variables.
Results: A total of 101 patients were included (TBW n=40; ABW n=61). Several differences in baseline characteristics existed between groups; the ABW cohort was significantly older (60.8 vs 56.1 years; p=0.025), had a higher mean BMI (38.7 vs 36.1 kg/m2; p=0.041), and had a higher prevalence of concomitant statin use (45.9% vs 20.0%). The primary composite safety outcome occurred in 20.0% (n=8/40) of TBW vs 19.7% (n=12/61) of ABW patients (p=0.78). CK elevation occurred in 20.0% vs 16.4% (p=0.59), myopathy in 5.0% vs 4.9% (p=1.00), and rhabdomyolysis in 2.5% vs 0% (p=0.39) in TBW and ABW groups, respectively. Discontinuation due to safety concerns occurred in 15.0% vs 8.2% (p=0.34). Ninety-day mortality was 20.0% vs 16.4% (p=0.64). There were no significant differences in secondary outcomes.
Conclusions: In this cohort of obese patients receiving high-dose daptomycin, TBW and ABW based dosing strategies demonstrated similar rates of composite safety events, as well as exploratory efficacy outcomes.
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