Ceftaroline: An Alternative Broad Spectrum Antibiotic for Pediatric Infections

Marcia L. Buck, PharmD, FCCP, FPPAG, BCPPS

Disclosures

Pediatr Pharm. 2017;23(6) 

In This Article

Clinical Experience in Pediatrics

The manufacturer submitted a series of clinical studies showing the safety and efficacy of ceftaroline in pediatric patients to gain approval for use in children from the FDA and the European Medicines Agency. Cannavino and colleagues enrolled 161 children with CABP in a multicenter, randomized comparator-controlled trial.[7] Patients in the 34 study centers were randomized in a 3:1 ratio to receive ceftaroline or ceftriaxone for a minimum of 72 hours or 3 study days, at which point the patients could be switched to oral amoxicillin/clavulanate, and a maximum of 14 days. Patients were stratified by age into four cohorts: 2 to 23 months, 2 years to < 6 years, 6 to < 12 years, and 12 to < 18 years. Patients younger than 6 months of age received a dose of 8 mg/kg every 8 hours, while older patients weighing 33 kg or less received 12 mg/kg and those weighing more than 33 kg received 400 mg every 8 hours. All doses were infused over 60 minutes. Patients in the ceftriaxone group received a dose of 75 mg/kg/day (maximum 4 g/day) divided and given every 12 hours using a 30-minute infusion.

In the modified intent-to-treat population of 143 children, clinical cure rates at test of cure were 87.9% for ceftaroline and 88.9% for ceftriaxone, with a treatment difference of −1.0 (95% CI −11.5, 14.1). While the study supported the efficacy of ceftaroline in this cohort of children, it was not powered to identify a statistically significant difference from standard treatment. Rates of adverse effects were similar, with 10% of the ceftaroline group and 8% of the ceftriaxone group experiencing a drug-related adverse effect. Serious adverse effects were infrequent, occurring in six patients in the ceftaroline group (5%) and 1 patient in the ceftriaxone group (3%). The most frequently reported adverse effect was diarrhea. In the 112 patients with a negative Direct Coombs' test at baseline, 19 (17%) of patients in the ceftaroline group and 1 of the 37 patients in the ceftriaxone group seroconverted during treatment. There were no cases of hemolytic anemia.

The pediatric CABP indication was further supported by the study conducted by Blumer and colleagues in 40 children between 2 and 17 years of age.[8] This randomized parallel-group study compared ceftaroline to the combination of ceftriaxone and vancomycin in the treatment of complicated CABP infections. The median duration of treatment prior to switching to a more narrow-spectrum antibiotic was 9 days (range 2 to 19 days) in the ceftaroline group and 7.5 days (5–13 days) in the ceftriaxone/vancomycin group. Clinical response rates in the modified intent-to-treat population were 82.8% and 77.8% in the two groups, respectively, with a treatment difference of 5% (95% CI −19.9, 40.3). Drug-related adverse effects were reported in seven ceftaroline patients and four patients in the comparator group. Two patients in the ceftaroline group discontinued treatment; one for elevated serum transaminases and one for a rash and pruritus. Direct Coombs' test seroconversion was reported in 6/23 (26%) ceftaroline patients. As in the previous study, there were no reports of hemolytic anemia.

The efficacy and safety of ceftaroline in pediatric ABSSSI was established in a study by Korczowski and colleagues.[9] One hundred sixty-three children between 2 and 17 years of age were randomized to receive either vancomycin or cefazolin (with or without aztreonam) for a period of 5 to 14 days. Efficacy was assessed in the 159 patients in the modified intent-to-treat population. As in the CABP studies, clinical cure rates at the test of cure visit (8–15 days after the end of treatment) were similar between the groups: 94.4% in the ceftaroline group and 86.5% in the combined comparator group, with a treatment difference of 7.9 (95% CI −1.2, 20.2). There were no clinical failures reported in the ceftaroline group and only one case in the comparator group. The only serious drug-related adverse effect reported was hypersensitivity in a patient in the ceftaroline group. Direct Coombs' test seroconversion was documented in 17 of the 99 (17%) previously negative patients. There were no cases of hemolytic anemia reported.

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