In the Journals

Daptomycin safe, effective treatment for children with gram-positive skin infections

Compared with standard of care, once-daily daptomycin, a parenteral lipopeptide antibiotic, demonstrated significant effectiveness and safety for the treatment of complicated skin and skin structure infections caused by gram-positive pathogens, including community-acquired methicillin-resistant Staphylococcus aureus.

“Clinical trials have established the safety and efficacy of daptomycin for treating complicated skin and skin structure infections in adults,” John Bradley, MD, director of the Division of Infectious Diseases at Rady Children’s Hospital-San Diego, and colleagues wrote.Pharmacokinetic studies demonstrated that children require higher daptomycin doses — varying by age — to achieve steady-state exposure comparable to adult plasma levels associated with treatment success. Substantial clinical and safety data regarding daptomycin use in pediatric patients are still lacking.”

The evaluator-blinded clinical trial intended to assess both the safety and efficacy of daptomycin compared with standard of care. All patients who were randomly assigned, who were aged 1-17 years old and received any dose of the study drug, were part of the intent-to-treat population. The trial included multiple centers of care.

Each patient, who presented with complicated skin and skin structure infections caused by gram-positive pathogens, was randomly assigned to two groups with a 2:1 ratio of intravenous daptomycin or standard care for less than or equal to 14 days. Doses of the drug were dependent on the patient’s age: 12 to 23 months received 10 mg/kg, 2 to 6 years received 9 mg/kg, 7 to 11 years received 7 mg/kg and 12 to 17 years received 5 mg/kg.

The patient population included in the trial contained 257 who were treated with daptomycin and 132 who were treated with standard care. Those treated with standard care were primarily administered clindamycin or vancomycin. Thirty-five percent of patients presented with confirmed methicillin-resistant S. aureus (MRSA). Diarrhea (7% daptomycin, 5% standard care) and increased creatine phosphokinase (6% daptomycin, 5% standard care) were the most common adverse effects to treatment.

The amount of safety population patients with negative effects from treatment were comparable between daptomycin (14%) and standard of care (17%), and the success rates of clinical treatment in the intent-to-treat population were also similar for the daptomycin (91%) and standard-of-care groups. These rates were determined by a blind evaluator that assessed complete and partial resolution of complicated skin and skin structure infections signs and symptoms for 7 to 14 days after treatment was completed.

“Daptomycin may be particularly suitable as an alternative to vancomycin for MRSA therapy because the higher vancomycin doses recommended for treating methicillin-resistant pathogens can cause deteriorating renal function while the patient is on therapy,” researchers wrote. “Daptomycin may also represent an alternative to empiric clindamycin resistance — for either MRSA or [methicillin-resistant S. aureus] — and/or in children with a greater severity of illness, in whom potential resistance can limit clindamycin’s utility as empirical therapy. Given the lack of resistance concerns with daptomycin, this agent may be especially valuable if the causative pathogen is not known to be susceptible.” – by Katherine Bortz

Disclosure: Drs. Bradley, Arnold, Arrieta, Congeni, Duam and Kojaoghlanian participated as study site principal investigators in this clinical trial. Their respective employers received institutional research funding from the study sponsor, Cubist Pharmaceuticals (now part of Merk & Co, Inc, Kenilworth, NJ), in support of the trial.

Compared with standard of care, once-daily daptomycin, a parenteral lipopeptide antibiotic, demonstrated significant effectiveness and safety for the treatment of complicated skin and skin structure infections caused by gram-positive pathogens, including community-acquired methicillin-resistant Staphylococcus aureus.

“Clinical trials have established the safety and efficacy of daptomycin for treating complicated skin and skin structure infections in adults,” John Bradley, MD, director of the Division of Infectious Diseases at Rady Children’s Hospital-San Diego, and colleagues wrote.Pharmacokinetic studies demonstrated that children require higher daptomycin doses — varying by age — to achieve steady-state exposure comparable to adult plasma levels associated with treatment success. Substantial clinical and safety data regarding daptomycin use in pediatric patients are still lacking.”

The evaluator-blinded clinical trial intended to assess both the safety and efficacy of daptomycin compared with standard of care. All patients who were randomly assigned, who were aged 1-17 years old and received any dose of the study drug, were part of the intent-to-treat population. The trial included multiple centers of care.

Each patient, who presented with complicated skin and skin structure infections caused by gram-positive pathogens, was randomly assigned to two groups with a 2:1 ratio of intravenous daptomycin or standard care for less than or equal to 14 days. Doses of the drug were dependent on the patient’s age: 12 to 23 months received 10 mg/kg, 2 to 6 years received 9 mg/kg, 7 to 11 years received 7 mg/kg and 12 to 17 years received 5 mg/kg.

The patient population included in the trial contained 257 who were treated with daptomycin and 132 who were treated with standard care. Those treated with standard care were primarily administered clindamycin or vancomycin. Thirty-five percent of patients presented with confirmed methicillin-resistant S. aureus (MRSA). Diarrhea (7% daptomycin, 5% standard care) and increased creatine phosphokinase (6% daptomycin, 5% standard care) were the most common adverse effects to treatment.

The amount of safety population patients with negative effects from treatment were comparable between daptomycin (14%) and standard of care (17%), and the success rates of clinical treatment in the intent-to-treat population were also similar for the daptomycin (91%) and standard-of-care groups. These rates were determined by a blind evaluator that assessed complete and partial resolution of complicated skin and skin structure infections signs and symptoms for 7 to 14 days after treatment was completed.

“Daptomycin may be particularly suitable as an alternative to vancomycin for MRSA therapy because the higher vancomycin doses recommended for treating methicillin-resistant pathogens can cause deteriorating renal function while the patient is on therapy,” researchers wrote. “Daptomycin may also represent an alternative to empiric clindamycin resistance — for either MRSA or [methicillin-resistant S. aureus] — and/or in children with a greater severity of illness, in whom potential resistance can limit clindamycin’s utility as empirical therapy. Given the lack of resistance concerns with daptomycin, this agent may be especially valuable if the causative pathogen is not known to be susceptible.” – by Katherine Bortz

Disclosure: Drs. Bradley, Arnold, Arrieta, Congeni, Duam and Kojaoghlanian participated as study site principal investigators in this clinical trial. Their respective employers received institutional research funding from the study sponsor, Cubist Pharmaceuticals (now part of Merk & Co, Inc, Kenilworth, NJ), in support of the trial.