Over the past decades, the incidence of healthcare-associated infections has risen, notably due to multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) [1,2]. Glycopeptide antibiotics, long considered standard therapy, are now challenged by emerging resistance and nephrotoxicity, especially in elderly or frail patients. Daptomycin, a cyclic lipopeptide antibiotic approved in 2006 by the U.S. Food and Drug Administration (FDA), was initially recommended at 4 mg/kg/day for skin and soft tissue infections (SSTIs) [3]. It was later shown to be non-inferior to standard therapy for S. aureus bacteremia and right-sided endocarditis at 6 mg/kg/day [4]. Subsequent data support better efficacy of higher doses (>8 mg/kg/day) for bloodstream infections (BSIs) [5].

In France, the Surveillance and Prevention of Antimicrobial Resistance in Healthcare Facilities (SPARES) network reported a 1090% increase in daptomycin use between 2012 and 2021, mainly for osteomyelitis and BSIs, but not SSTIs. In addition, daptomycin is known to be ineffective in pneumonia due to surfactant inactivation [6].

Muscle toxicity is a well-described adverse effect, with creatine kinase (CK) elevations in 2.8–7.3% and rhabdomyolysis in <1% of cases [7]. Although rare, rhabdomyolysis, but also acute renal failure and eosinophilic pneumonia have been documented as serious complications [7]. Rhabdomyolysis is characterized clinically by the triad of myalgias, muscle weakness, and red to brown urines due to myoglobinuria associated to CK elevation [8]. While no absolute cut-off value for CK elevation is defined, serum CK is usually >5000 IU/L with non-exertional rhabdomyolysis and >10,000 IU/L with exertional rhabdomyolysis. Risk factors include elevated daptomycin trough concentrations (Cmin ≥ 24.3 mg/L), prolonged treatment, obesity, statin use, and pre-existing muscular disorders [9].

This study aims to provide real-world data from three French university hospitals, focusing on safety monitoring practices and factors associated with rhabdomyolysis in patients treated with daptomycin.