FDA Approves Antibiotic Ceftobiprole Medocaril for Injection for 3 Indications

The FDA has approved antibiotic ceftobiprole medocaril sodium for injection (Zevtera) for 3 indications: the treatment of adults with Staphylococcus aureus bacteremia (SAB), including right-sided infective endocarditis; the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI), and the treatment of adults and children aged 3 months to 18 years with community-acquired bacterial pneumonia (CABP), according to a news release.¹

Staphylococcus aureus Bacteremia

The agency’s approval of ceftobiprole medocaril sodium for SAB was based on data from a randomized, controlled, double-blind, multinational, multicenter clinical trial (NCT03138733). Investigators randomly assigned patients (N=390) to receive either ceftobiprole medocaril sodium or daptomycin plus optional aztreonam (n=192 and 198, respectively). The primary efficacy measure was overall success of the antibiotic at a post-treatment evaluation visit 70 days after being randomly assigned to a treatment group.

Overall success was defined as survival, symptom improvement, S aureus bacteremia bloodstream clearance, no new S aureus complications, and no use of other potentially effective antibiotics. Results demonstrated that 69.8% of patients in the ceftobiprole medocaril sodium group achieved overall success, compared with 68.7% in the comparator group.

The most common adverse effects in this patient population included anemia, nausea, hypokalemia, vomiting, diarrhea, increased hepatic enzymes and bilirubin, increased blood creatinine, elevated blood pressure, leukopenia, and dyspnea, among others.

ABSSSI

Efficacy of ceftobiprole medocaril sodium in treating ABSSSI was evaluated in a randomized, controlled, double-blind, multinational trial (NCT03137173). Investigators randomly assigned patients (N=679) to receive either ceftobiprole medocaril sodium or vancomycin plus aztreonam (n=335 and 344, respectively). The primary efficacy measure was early clinical response in the 48 to 72 hours following treatment initiation.

Early clinical response included a reduction of the primary skin lesion by at least 20%, survival for at least 72 hours, and the absence of additional antibacterial treatment or unplanned surgery. In the treatment group, 91.3% of patients achieved an early clinical response, compared with 88.1% of patients in the comparator group.

The most common adverse effects of ceftobiprole medocaril sodium include nausea, diarrhea, injection site reaction, increased hepatic enzymes, and dysgeusia, among others.

CABP

The efficacy of ceftobiprole medocaril sodium in treating adults with CAPB was evaluated in a randomized, controlled, double-blind, multinational, multicenter clinical trial (NCT00326287). A total of 638 hospitalized adults with CABP requiring intravenous antibacterial treatment were randomly assigned to receive either ceftobiprole medocaril sodium (n=314) or ceftriaxone with optional linezolid (n=324). The primary efficacy measure was clinical cure rate at test-of-cure visit, which took place 7 to 14 days after treatment ended.

In the ceftobiprole medocaril sodium group, 76.4% of patients achieved clinical cure, vs 29.3% in the comparator group. An additional analysis, considering clinical success at day 3, was also conducted: 71% of patients in the ceftobiprole medocaril sodium group achieved clinical success compared with 71.1% in the comparator group within the shortened time frame.

Because the course of CABP is similar in adults and pediatric patients, the ceftobiprole medocaril sodium approval in pediatric populations was supported by data from the adult trial and a clinical trial of 138 pediatric patients with pneumonia (NCT03439124).

In adults with CABP, the some of most common adverse effects of treatment with ceftobiprole medocaril sodium included increased hepatic enzymes, phlebitis, and dizziness; common adverse effects were similar for children with CABP.

Warnings and precautions of ceftobiprole medocaril use include increased mortality when used to treat ventilator-associated bacterial pneumonia, which is an unapproved use; hypersensitivity reactions, seizures and other central nervous system reactions, and Clostridioides difficile-associated diarrhea.

The FDA granted ceftobiprole medocaril both priority review and fast track and qualified infectious disease product designations for all 3 indications.

Reference

1. FDA approves new antibiotic for three different uses. News release. FDA. April 3, 2024. Accessed April 4, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibiotic-three-different-uses