Daptomycin as Effective as Standard of Care in Children with Bacteremia
NEW ORLEANS, LA—Daptomycin was as effective as standard of care in treating Staphylococcus aureus bacteremia in children aged 1–17 years of age, according to study results reported at IDWeek 2016.
“S. aureus is a major cause of bacteremia in adolescents and children and is a growing health concern because it is associated with high morbidity and mortality rates in adult and pediatric patients,” noted Antonio Arrieta, MD, Director, Pediatric Infectious Diseases at Children's Hospital of Orange County, Orange, CA.
In clinical studies in adults, daptomycin was safe and non-inferior to standard of care comparator agents; however, data in the pediatric population are lacking. To compare daptomycin vs. standard of care in pediatric patients aged 1–17 years of age, Dr. Arrieta and colleagues randomly assigned 81 patients with bacteremia—73 (90.1%) with S. aureus and 8 (9.9%) with coagulase-negative Staphylococcus—in a 2:1 ratio to intravenous daptomycin (n=55) or standard of care: vancomycin, a semi-synthetic penicillin, a first-generation cephalosporin, or clindamycin (n=26).
The primary end point of the open-label study was safety, as analyzed by the incidence of adverse events. Secondary end points were favorable clinical response, defined as cure/improvement at the test of cure visit, and overall therapeutic success, defined as combined favorable clinical and microbiological response at the test of cure visit, based on blinded evaluator assessments.
The doses of daptomycin varied by age, with the goal of achieving exposures similar to adults. For those aged 1–6 years, daptomycin 12mg/kg once daily was administered; for 7–11 years, 9 mg/kg once daily; and those 12–17 years, 7mg/kg once daily.
“Patients received 5–42 days of the study drug, depending on the source of infection, presence of endovascular infection, and metastatic foci of infection,” Dr. Arrieta reported.
The baseline pathogen was methicillin susceptible S. aureus in 44 (80.0%) of the daptomycin-treated patients and 19 (73.1%) in those who received standard of care. Other baseline pathogens were methicillin-resistant S aureus, coagulase-negative Staphylococcus, other Staphylococcus species, and unknown. The most commonly identified underlying infections were catheter-related, osteomyelitis, arthritis bacterial, and peritonitis.
Median age was 9.6 years (range 2.0–16.9 years) in the daptomycin arm and 8.8 years (range 2.0–17.6 years) in the standard of care arm; in both groups, the majority were male, 69.1% and 61.5%, respectively.
Rates of treatment-related adverse events were similar between arms; 8 (14.5%) patients in the daptomycin arm and 4 (15.4%) in the standard of care arm had one or more such event, which included diarrhea and increase in creatinine phosphokinase. No severe or serious treatment-related adverse events, including deaths, were observed.
At the test of cure visit, 45 of the 51 (88.2%) evaluable patients in the daptomycin arm and 17 of 22 (77.3%) in the standard of care arm had favorable clinical response. Overall success was observed in 37 of 51 (72.5%) patients treated with daptomycin and 13 of 22 (59.1%) who received standard of care. Patients who were 7–11 years of age and treated with daptomycin had the highest overall success rate, 82.4%, while those in the same age group treated with standard of care agents had the lowest rate, 44.4%. The study authors noted that these results “should be interpreted with caution because of the small sample sizes.”
Regardless of treatment arm, those who were 12–17 years of age had generally lower overall success rates than those who were 1–6 or 7–11 years of age.
The study was not powered to detect statistical differences between arms.
The study was funded by Merck & Co., Inc.