Ceftobiprole Receives FDA Approval, Enhancing Antibiotic Options


Dr. Thomas Holland discusses the breakthrough in antibiotic development.

Ceftobiprole was non-inferior to daptomycin regarding overall treatment success in patients with Staphylococcus aureus bacteremia.

The results were consistent across key subgroups and for secondary outcomes, including mortality rates (9.0% for ceftobiprole and 9.1% for daptomycin; 95% CI, −6.2 to 5.2) and microbiologic eradication rates (82.0% for ceftobiprole and 77.3% for daptomycin; 95% CI, −2.9 to 13.0). Adverse events occurred in 121 out of 191 patients (63.4%) treated with ceftobiprole 117 out of 198 patients (59.1%) treated with daptomycin, with serious adverse events reported in 36 (18.8%), and 45 (22.7%) patients, respectively.

Investigator Thomas Holland, MD, Associate professor of infectious diseases at Duke University offers a deeper insight into the antibiotic and its approval.

“Just approved by the FDA for treatment of several different types of bacterial infections,” says Holland. “The antibiotic is in a class of antibiotics called cephalosporin. It's what's called a fifth-generation or Advanced Generation cephalosporin. And one of the things that is relatively unique about it is that it is active against a bacteria called methicillin-resistant S aureus. So it was studied in several different types of infections, and one of the indications that was approved for was for treatment of S aureus bacteremia.”

Main Takeaways

  1. Ceftobiprole is non-inferior to daptomycin in treating patients with S aureus bacteremia, including those caused by MRSA.
  2. The study findings were consistent across key subgroups and secondary outcomes such as mortality and microbiologic eradication rates.
  3. The FDA's approval of ceftobiprole for treating several bacterial infections marks a significant advancement in the arsenal against difficult-to-treat bacteria like MRSA. The medical community's anticipation regarding how ceftobiprole will be incorporated into treatment algorithms highlights its potential to change the current approach to managing bacterial infections.

In this phase 3 trial, adults with S aureus bacteremia were assigned randomly in a 1:1 ratio to receive either ceftobiprole at a dose of 500 mg every 6 hours for 8 days and then every 8 hours, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight every 24 hours plus optional aztreonam, at the discretion of the investigators. The primary outcome, treatment success 70 days after randomization (defined as survival, clearance of bacteremia, symptom improvement, no new S aureus bacteremia–related complications, and no use of other antibiotics), with a noninferiority margin of 15%, was assessed by a committee unaware of the assignments. Safety was assessed.

“There are a few antibiotics available that can treat S aureus bacteremia, especially those cases caused by MRSA, or methicillin-resistant S aureus. Ceftobiprole was compared directly in a randomized trial with one of these antibiotics, daptomycin. This trial involved 390 patients with S aureus bacteremia from multiple countries around the world. Patients were randomized to receive either ceftobiprole or daptomycin. The main outcome was that ceftobiprole was non-inferior to daptomycin, meeting the criteria for success that had been established beforehand with the FDA.”

387 patients (189 in the ceftobiprole group and 198 in the daptomycin group) were confirmed to have S aureus bacteremia and received treatment (modified intention-to-treat population). In the ceftobiprole group, 132 out of 189 patients (69.8%) achieved overall treatment success, compared with 136 out of 198 patients (68.7%) in the daptomycin group (adjusted difference, 2.0 percentage points; 95% (CI), −7.1 to 11.1).

“I think it remains to be seen how the clinical community will incorporate this into treatment algorithms. I think it will be most attractive and most likely to get used in patients where there's concern for MRSA. Again, a type of infection or bacteria that causes infections that currently are hard to treat and improve outcomes are not as good as we would like. So, I suspect that's where its initial use is likely to be concentrated.”

More on the FDA approval can be found on Contagion’swebsite.


Holland T, Cosgrove S, Doernberg S, et. al. Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia. The New England Journal of Medicine. Published September 27, 2023. Accessed April 3, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2300220

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