Daptomycin for Complicated Skin Infections: A Randomized Trial

Abstract

Once-daily daptomycin was well tolerated, with safety and efficacy comparable to SOC in children/adolescents with cSSSI caused by Gram-positive pathogens, including community-acquired methicillin-resistant .

Pharmacokinetics of Daptomycin in Critically Ill Pediatric Patients

“…Despite administration of a higher dose of daptomycin (10 mg/kg QD), the AUC 0 -∞ values obtained on day 1 for the three septic patients in our study (patients 2, 3, and 4) were either comparable (patient 3) or markedly lower (patients 2 and 4) than those reported for pediatric cSSTI patients. These findings are consistent with the significantly higher clearance values obtained for daptomycin in these patients compared to those in the pediatric cSSTI patients (16 and 13 ml/h/kg for those aged 7 to 11 and 12 to 17 yrs, respectively) (5). Taken together, these results suggest an alteration of pharmacokinetics of daptomycin in pediatric patients with sepsis, characterized by increased clearance and suboptimal AUC values.…”

“…A dose of 4 mg/kg QD results in a mean AUC 0 -24 on day 7 of 494 g · h/ml (13). In pediatric patients with cSSTI, comparable exposures were obtained following administration of 7 mg/kg QD and 5 mg/kg QD in those aged 7 to 11 yrs and 12 to 17 yrs, respectively (5). Despite administration of a higher dose of daptomycin (10 mg/kg QD), the AUC 0 -∞ values obtained on day 1 for the three septic patients in our study (patients 2, 3, and 4) were either comparable (patient 3) or markedly lower (patients 2 and 4) than those reported for pediatric cSSTI patients.…”

“…Most of the pediatric pharmacokinetic studies of daptomycin published to date have focused on single-dose pharmacokinetics (2)(3)(4). In a recently published randomized controlled trial evaluating the safety and efficacy of daptomycin for complicated skin and skin structure infections in children, multiple-dose pharmacokinetic analysis was performed in 6 patients (12 to 17 yrs old) receiving 5 mg/kg, 2 patients 7 to 11 yrs old receiving 7 mg/kg, 7 patients (2 to 6 yrs old) receiving 9 mg/kg, and 30 patients (12 to 23 months old) receiving 10 mg/kg of daptomycin once daily (QD) (5). The pediatric dosages approved by the FDA and EMA are 5, 7, 9, and 10 mg/kg QD, respectively, for patients aged 12 to 17, 7 to 11, 2 to 6, and 1 to Ͻ2 yrs old.…”

Community-Acquired MRSA Pericarditis and Mediastinitis in a Previously Healthy Infant

“…[21][22][23][24] The first randomized trial of daptomycin for complicated skin infections in children, which included nearly 100 children with MRSA, reported clinical success rates of 91%, similar to that of the standard-of-care antimicrobial agent. 25 Adverse events in all of these studies were minimal and included diarrhea and elevated creatine phosphokinase. 19,[21][22][23][24][25][26][27][28] Eosinophilic pneumonia is a reported adverse event in adults, but has not been reported in children.…”

“…25 Adverse events in all of these studies were minimal and included diarrhea and elevated creatine phosphokinase. 19,[21][22][23][24][25][26][27][28] Eosinophilic pneumonia is a reported adverse event in adults, but has not been reported in children. 7,29 A wide gap remains between antibiotic regimens available to adults and children, demonstrating a need for further studies in the pediatric population.…”