Safety of high-dose daptomycin in obese patients: a multicentric retrospective study.

PURPOSE: Obese patients treated with daptomycin at 4 mg/kg have a 30% increased drug exposure, potentially raising the risk of adverse events (AEs) like rhabdomyolysis. Given limited data on the safety of higher doses (10 mg/kg) in this population, this study aimed to assess the safety of high-dose daptomycin in obese patients and to identify potential AEs risk factors.

METHODS

This multicenter, retrospective observational study was conducted from June 2021 to May 2022 using medical records. Patients with a BMI > 30 kg/m2 were classified as obese. AEs assessed included: CK elevation (> 5x upper limit of normal), severe elevation (> 10x upper limit), eosinophilic pneumonia, and elevated liver enzymes. Both univariate and multivariate analyses were conducted.

RESULTS

A total of 1 303 patients were included: 970 non-obese and 333 Ob patients. These patients received an average daptomycin dose of 9.9 mg/kg based on actual body weight for an average treatment duration of 8.27 days. One-third of the patients had CK monitoring. AEs rates were 3.5% for the n-Ob group vs. 8.7% in the Ob group (p < 0.01). Ob patients had significantly higher CK levels (n-Ob, 9.5%; Ob, 20.3%; p = 0.001), and severe elevation (n-Ob, 5.2%; Ob, 10.9%; p = 0.03). Factors increasing AE risk included obesity, concomitant prescriptions of drugs with risk of rhabdomyolysis, eGFR 30-60 mL/min, and daptomycin duration (OR = 2.42; 4.34; 2.03 and 1.05, respectively, p < 0.001). On the opposite, consultation with an infectious disease specialist reduced risk (OR = 0.52, p = 0.024).

CONCLUSION

This study highlights that obese patient has a significantly increased risk of AEs with high dose of daptomycin compared to non-obese patients. Adjusted body weight dosing may be considered to reduce AEs risk.