FDA OKs Injectable Antibiotic for Three Different Uses

The FDA approved the injectable drug ceftobiprole medocaril sodium (Zevtera) to treat adults with Staphylococcus aureus bacteremia (SAB), the agency announced Wednesday.

The antibiotic prodrug is indicated for people with right-sided infective endocarditis, those with acute bacterial skin and skin structure infections (ABSSSI), and adult and pediatric patients 3 months to less than 18 years old with community-acquired bacterial pneumonia (CABP). Ceftobiprole, a pyrrolidinone cephalosporin antibiotic, is the active moiety of the prodrug ceftobiprole medocaril.

"The FDA is committed to fostering new antibiotic availability when they prove to be safe and effective, and Zevtera will provide an additional treatment option for a number of serious bacterial infections," Peter Kim, MD, director of the agency's division of anti-infectives, said in a press release.

Ceftobiprole medocaril's efficacy in treating SAB was evaluated in a randomized controlled multinational trial involving 390 participants assigned to receive either the drug or daptomycin plus optional aztreonam. A total of 69.8% of participants who received ceftobiprole medocaril achieved overall success -- defined as survival, symptom improvement, bloodstream clearance of SAB, and no new complications -- compared with 68.7% of those who received a comparator.

The drug's efficacy in treating ABSSSI was evaluated in a multinational trial in which 679 participants were randomly assigned to receive either ceftobiprole medocaril or vancomycin plus aztreonam. Of those who received ceftobiprole medocaril, 91.3% achieved an early clinical response -- reduction of primary skin lesion by at least 20%, survival for at least 72 hours, and no additional antibacterial treatment or unplanned surgery within the necessary 48-to-72-hour timeframe -- compared with 88.1% of people who received a comparator.

Ceftobiprole medocaril's efficacy in treating adult patients with CABP was evaluated in a multinational trial of 638 adults hospitalized with CABP and requiring IV antibacterial treatment for at least 3 days who were randomly assigned to receive either ceftobiprole medocaril or ceftriaxone with optional linezolid. Of those who received the former, 76.4% achieved clinical cure 7-to-14 days after treatment ended, compared with 79.3% of people who received the comparator. An additional analysis looked at an earlier timepoint of clinical success at day 3, which was 71% in patients receiving the study drug and 71.1% in patients receiving the comparator.

The approval of ceftobiprole medocaril also was supported by evidence from the CABP trial of ceftobiprole medocaril in adults and a trial in 138 pediatric participants 3 months to less than 18 years of age with pneumonia, the agency said.

Patients should not use the antibiotic if they have a known history of severe hypersensitivity to ceftobiprole or any of the components of this agent or other members of the cephalosporin antibacterial class.

Common side effects for those receiving the antibiotic for each of the three indications included nausea, vomiting, and diarrhea. Some participants with SAB experienced additional side effects including hypertension, leukopenia, fungal infection, headache, and dyspnea.

For pediatric patients with CABP, the most common side effects of ceftobiprole medocaril included vomiting, headache, increased levels of hepatic enzymes, diarrhea, infusion site reaction, phlebitis, and fever.

FDA approval of ceftobiprole medocaril was granted to Basilea Pharmaceutica International.

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