LEIPZIG, Germany ― Daptomycin (Cubicin, Cubist Pharmaceuticals) is safe and effective for the treatment of complicated skin infections in children, according to the results of a trial presented here at the 33rd Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID).
The drug is already approved by the US Food and Drug Administration for complicated skin infections in adults, as well as for Staphylococcus aureus and methecillin-resistant S. aureus (MRSA) bloodstream infections, but it is not currently available for use in children.
"We found that daptomycin and the standard of care group exhibited comparably high success rates, with daptomycin patients requiring fewer days of IV therapy," said coauthor John Bradley, MD, from the Rady Children's Hospital and the University of California, San Diego.
With multidrug-resistant bacteria an ever-increasing threat to adult and younger patients alike, daptomycin has gained value as a powerful bactericidal, with a highly potent antibiotic effect against gram-positive pathogens in adults.
Dr Bradley and his team conducted a multicenter, randomized, phase 3 trial comparing treatment with daptomycin to the standard of care in children with complicated skin and skin structure infections.
Patients in the daptomycin group (n = 263) were treated with once-daily age-adjusted intravenous doses. Patients in the standard of care group (n = 133) received either clindamycin (multiple brands) (50.4%) or vancomycin (42.1%).
Table. Age-Adjusted IV Doses of Daptomycin
| Age (years) | Dose (mg/kg) | Infusion Time (minutes) |
| 1 to 2 | 10 | 60 |
| 2 to 6 | 9 | 60 |
| 7 to 11 | 7 | 30 |
| 12 to 17 | 5 | 30 |
There were no significant differences between the two groups in terms of treatment-emergent adverse events, the study's primary endpoint, including treatment-emergent elevations in creatine phosphokinase levels (5.5% in the daptomycin group; 5.4% in the standard of care group).
For the secondary endpoints of clinical and microbiological success, patient assessments were made by a blinded evaluator 7 to 14 days following the end of the treatment regimen.
Clinical success was determined in 88.3% of patients in the daptomycin group and in 86.3% in the standard of care group.
The evaluator was permitted to switch the patients from IV to oral therapy if they showed clinical improvement, and Dr Bradley reported that 40.2% of patients in the daptomycin group did switch, receiving fewer than 3 days of IV therapy prior to oral conversion, compared with 30.1% of patients in the standard of care group.
For the microbiologic assessment, 167 patients in the daptomycin group and 78 in the comparison arm were evaluable.
There were no significant differences in microbiologic success rates for the daptomycin (98.1%) and standard of care groups (98.6%). Success in the treatment of MRSA was also similar (97.1% for the daptomycin group; 100% for the standard of care group).
"Daptomycin given at age-appropriate doses is efficacious, safe, and generally well tolerated for the treatment of complicated skin and skin structure infections in children compared with the standard of care," Dr Bradley said.
He pointed out that, owing to concerns of neurologic abnormalities seen in some neonatal mouse models, daptomycin is currently not being studied in children younger than 1 year, a restriction that is indicated on the product label.
Susanna Esposito, MD, who was comoderator of the session, recently published a review in the Journal of Antimicrobial Chemotherapy of the need for a drug such as daptomycin in children.
"Daptomycin is a promising therapeutic option for the treatment of pediatric diseases due to multidrug-resistant gram-positive rods," said Dr Esposito, from the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, in Milan, Italy.
"Research establishing adequate dosage for different pediatric ages is essential before daptomycin is approved for use in children, and even more work is needed to determine how the drug can benefit neonates and younger infants," said Dr Esposito.
"No adequate studies of the pharmacokinetics, tolerability, and safety of daptomycin are planned in neonates and younger infants," she said.
"These studies are urgently needed to permit the use of daptomycin in the first months of life, a period in which infections due to multidrug-resistant gram-positive pathogens are increasing," she added.
This study was funded by Merck. Dr Bradley and Dr Esposito report no relevant financial relationships.
33rd Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID). Abstract 121. Presented May 14, 2015.
Medscape Medical News © 2015 WebMD, LLC
Send comments and news tips to news@medscape.net.
Cite this: Daptomycin Safe for Children With Skin Infections - Medscape - May 18, 2015.
Comments