Postapproval Surveillance Confirms Ceftobiprole Activity Against MRSA

The first US surveillance data collected after the FDA approval of ceftobiprole (Zevtera; Innoviva Specialty Therapeutics) show the advanced-generation cephalosporin retains activity against nearly all methicillin-resistant Staphylococcus aureus (MRSA). In a poster presented at IDWeek 2026, investigators with the SENTRY Antimicrobial Surveillance Program reported about 99% of MRSA isolates collected at US medical centers in 2025 were susceptible to ceftobiprole.¹

Gram-negative results were more mixed. Ceftobiprole inhibited 73% of Escherichia coli and Klebsiella pneumoniae isolates overall, compared with near-complete activity against isolates without an extended-spectrum β-lactamase (ESBL) phenotype.¹ The gap places ESBL risk at the center of empiric decisions in pneumonia and mixed infections.

The FDA approved ceftobiprole in April 2024 for 3 indications: S aureus bacteremia, including right-sided infective endocarditis, in adults; acute bacterial skin and skin structure infections in adults; and community-acquired bacterial pneumonia in adults and pediatric patients 3 months to younger than 18 years.² The bacteremia indication rested on the phase 3 ERADICATE trial, published in The New England Journal of Medicine, in which ceftobiprole was noninferior to daptomycin with or without aztreonam.³ Overall treatment success at day 70 was 69.8% (132/189) with ceftobiprole and 68.7% (136/198) with daptomycin.³

Innoviva acquired exclusive US marketing rights from Basilea Pharmaceutica in December 2024 and made the drug commercially available in May 2025.² The 2025 SENTRY collection offers clinicians the first contemporary look at susceptibility patterns since the agent entered routine use.

David Altarac, MD, chief medical officer at Innoviva Specialty Therapeutics, which markets ceftobiprole in the US, spoke with Contagion at IDWeek 2026 in Washington, DC. In the following interview, Altarac discusses the surveillance findings, empiric use when ESBL risk is present, and where ceftobiprole fits alongside ceftaroline.

Contagion: The 2025 SENTRY data show about 99% of MRSA isolates susceptible to ceftobiprole. How do these findings compare with preapproval susceptibility data?

Altarac: Ceftobiprole, or Zevtera, was approved, as you said, in 2024 based on a large randomized, controlled, double-blind study, where ceftobiprole was noninferior to the comparator in Staph bacteremia, including right-sided endocarditis, in both methicillin-susceptible Staph aureus and methicillin-resistant Staph aureus. The SENTRY findings are reassuring and consistent with the preapproval susceptibility data. We view these findings as an important continuation of the evidence rather than a new finding, and it underscores why surveillance matters. We need to know and follow contemporary isolates to monitor for the development of resistance. This is important as we move into clinical practice, to inform treatment decisions and continue to monitor for potential resistance development.

Contagion: Ceftobiprole inhibited 73% of E coli and K pneumoniae but nearly all non-ESBL isolates. How should this shape empiric use in pneumonia or mixed infections?

Altarac: Ceftobiprole has strong Gram-positive activity and activity against non-ESBL-producing Gram negatives. It is not an ESBL-directed agent. If a patient has high risk for ESBL (let’s say they’ve received prior antibiotics, they’ve been in a health care institution, they have an invasive device, or they’ve had a recent procedure), clinicians should account for those risks and select an appropriate agent. As the microbiologic data become more obvious, they can then adjust the medication to the most appropriate agent. These are really the underpinnings and the key points of antibiotic stewardship: to understand the likely pathogen, to know the patient’s specific risk factors and select the best agent, and then, based on microbiologic and local data, determine the best antibiotic to treat the patient.

Contagion: Where does ceftobiprole fit alongside ceftaroline for Staphylococcus aureus bacteremia?

Altarac: Data from this trial demonstrated efficacy in the treatment of staphylococcal bacteremia, including infections caused by methicillin-resistant and methicillin-susceptible Staphylococcus aureus. The FDA approval of ceftobiprole gives clinicians an option to use an anti-MRSA β-lactam agent as they make their treatment decisions. There are currently no head-to-head comparisons between ceftobiprole and ceftaroline.

Editor’s Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.

References

1. Mendes RE, Winkler M, Moussa SH, et al. In vitro activity of ceftobiprole and comparator agents against contemporary US clinical isolates collected in 2025 following FDA approval. Poster P-142. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC.

2. Innoviva Specialty Therapeutics. ZEVTERA (ceftobiprole), an advanced-generation cephalosporin antibiotic now commercially available in the U.S. to treat three types of bacterial infections. Published May 20, 2025. Accessed November 2, 2026. https://www.businesswire.com/news/home/20250520570730/en

3. Holland TL, Cosgrove SE, Doernberg SB, et al. Ceftobiprole for treatment of complicated Staphylococcus aureus bacteremia. N Engl J Med. 2023;389(15):1390-1401. doi:10.1056/NEJMoa2300220