Ceftobiprole on par with cephalosporin for treatment of paediatric pneumonia

A small phase III trial has found that ceftobiprole is well tolerated and as efficacious as standard-of-care (SoC) cephalosporins in paediatric patients with hospital- (HAP) or community-acquired pneumonia (CAP) requiring hospitalization.

“These findings suggest that ceftobiprole may be considered as an additional option for the treatment of pneumonia (excluding ventilator-associated pneumonia) in hospitalized paediatric patients,” the researchers said.

This multicentre, investigator-blinded, active-controlled, phase III study randomly assigned 134 patients aged 3 months to <18 years with HAP or CAP requiring hospitalization to ceftobiprole (n=94) vs SoC intravenous (IV) cephalosporin (n=44) treatments (ceftazidime or ceftriaxone), with or without vancomycin. After at least 3 days of IV treatment, patients demonstrating clinical improvement were switched to an oral antibiotic, to complete a minimum of 7 days’ treatment.

The median time to oral antibiotic switch was 6.0 days and 8.0 days in the ceftobiprole and the SoC cephalosporin groups, respectively. Adverse events (AEs) and treatment related AEs while on IV therapy were reported by 20.2 percent and 8.5 percent of ceftobiprole-treated patients and 18.2 percent and 0 percent of SoC cephalosporin-treated patients. [Pediatr Infect Dis J 2021;40:e222-e229]

“[T]he safety and tolerability findings for ceftobiprole in paediatric patients with HAP or CAP were consistent with the established safety profile for ceftobiprole in adults,” the researchers said. “AEs reported during ceftobiprole treatment tended to be mild or moderate in intensity and were most commonly gastrointestinal in nature; this is consistent with results published in adult populations.” [https://www.medicines.org.uk/emc/product/9164]

In the current study, only 4.3 percent stopped treatment with ceftobiprole due to AEs, suggesting that the study drug was well tolerated by most paediatric patients. This result was consistent with the rates of discontinuation for AEs reported in adult patients with CAP (5.8 percent), HAP (3.6 percent), and acute bacterial skin and skin structure infections. [Clin Infect Dis 2014;59:51-61; Int J Antimicrob Agents 2012;39:240-246; Clin Infect Dis 2020;doi:10.1093/cid/ciaa974]

In the intention-to-treat population, early clinical response rates at day 4 were 95.7 percent and 93.2 percent (between-group difference, 2.6 percent, 95 percent confidence interval [CI], –5.5 percent to 14.7 percent) in the ceftobiprole and comparator groups; clinical cure rates at the test-of-cure visit were 90.4 percent and 97.7 percent (between-group difference, –7.3 percent, 95 percent CI, –15.7 percent to 3.6 percent), respectively.

“Based on historical study data, achieving symptom improvement at day 4 is considered a relevant treatment response in CAP. As a result, it is endorsed by the US Food and Drug Administration as a primary outcome measure in clinical trials investigating new antibiotics for CAP,” the researchers said. [Clin Infect Dis 2012;55:1114-1121; https://www.fda.gov/regulatory-information/search-fda-guidance-documents/community-acquired-bacterial-pneumonia-developing-drugs-treatment]

“Clinical improvement at day 4 provides a useful indication of the comparative clinical efficacy of the two IV antibiotic approaches before the switch to physician-selected oral therapy has the potential to confound the comparison,” they added. [https://www.fda.gov/regulatory-information/search-fda-guidance-documents/community-acquired-bacterial-pneumonia-developing-drugs-treatment]