IV Daptomycin an Option for Children With Complicated Skin Infections

By Marilynn Larkin

February 16, 2017

NEW YORK (Reuters Health) - In children with complicated skin and skin structure infections caused by gram-positive pathogens, once-daily IV daptomycin is a safe, effective option, researchers say.

"Complicated skin and skin structure infections caused by community-acquired methicillin-resistant Staphylococcus aureus are common in children. Available treatments (e.g., vancomycin, clindamycin, and linezolid) can have important drawbacks, stressing the need for safer, uniformly active, and effective alternatives," Dr. John Bradley of the University of California, San Diego and colleagues write in Pediatrics, online February 15.

Dr. Bradley told Reuters Health that daptomycin, produced by Merck and marketed as Cubicin, "has demonstrated reasonable safety and efficacy for treatment of skin infections, including MRSA, in adults during the past 13½ years, but currently is not approved by FDA for treatment of children."

The current study showed the drug was comparable to comparison IV antibiotics used for hospitalized children, he said by email.

Dr. Bradley and colleagues randomized 257 pediatric patients to daptomycin and 132 to standard of care (SOC), primarily clindamycin (50%) or vancomycin (42%) for up to two weeks. Demographics and baseline characteristics were similar between the groups, with most patients (ages one to 17) presenting with a major abscess or complicated cellulitis.

Approximately 80% of patients in each arm had a gram-positive pathogen at baseline, and more than half of all baseline staphylococcal isolates were methicillin-resistant.

Daptomycin was given once daily with dosing by patient age: 12 to 17 year olds were given 5 mg/kg; 7 to 11, 7 mg/kg; 2 to 6, 9 mg/kg; and one year to 23 months old, 10 mg/kg.

Dr. Bradley explained, "the younger the age of child, the more rapidly they eliminated daptomycin from the serum compared with adults, so the actual mg/kg dose of daptomycin increased as the age of the research subjects decreased."

The duration of IV therapy was shorter with daptomycin, with 47% receiving fewer than three days compared with 35% of those on SOC. Five SOC patients, but no daptomycin patients, had to be changed to a different IV drug.

Most (95% daptomycin, 94% SOC) were switched to oral therapy, most commonly clindamycin (39% of those taking daptomycin and 35% of those on SOC.

The most frequent adverse events were diarrhea (7% in the daptomycin group, 5% in the SOC group) and increased creatine phosphokinase (6% daptomycin, 5% SOC). The proportions of patients with treatment-related adverse events were similar between the daptomycin (14%) and SOC (17%) groups. Clinical success rates - complete or partial resolution of signs and symptoms within one to two weeks after treatment ended - were also similar (91% daptomycin and 87% SOC). However, the trial was not powered to confirm noninferiority for daptomycin.

Dr. Bradley concluded, "Daptomycin, when approved by FDA for use in children, should provide a safe and effective alternative to vancomycin, clindamycin or linezolid for IV treatment of invasive MRSA skin infections. Concerns for vancomycin renal toxicity and clindamycin antibiotic resistance are not present with daptomycin. No evidence of daptomycin toxicity was apparent in the trial, (and there was no) drug-attributable muscle toxicity or neurologic toxicity in study subjects."

Dr. Alexander Hamling of Pacific Medical Centers in Seattle, Washington, told Reuters Health, "Daptomycin would likely be a second- or third-line therapy for those with severe complicated skin and skin structure infections, used only once sensitivities to daptomycin have been established."

"Larger studies would need be to be conducted to show at least noninferiority to the current standard of care," he said by email. "I would be more likely to choose this as an option if it showed better treatment than the standard of care."

The study was funded by Merck. Five coauthors were employees of Cubist Pharmaceuticals, now part of Merck, at the time of the trial. Three coauthors have received fees from Merck.

SOURCE: https://bit.ly/2linQtJ

Pediatrics 2017.

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