Activity of ceftobiprole against methicillin-resistant Staphylococcus aureus of diverse genetic types

Ceftobiprole was approved by the United States (US) Food and Drug Administration (FDA) in 2024 and by the European Medicines Agency in 2013 for the treatment of pneumonia, bacterial skin and skin structure infections, and Staphylococcus aureus bloodstream infections. Numerous methicillin-resistant S. aureus (MRSA) lineages have been identified with unique assemblages of resistance determinants and virulence factors.

MRSA isolates (n = 150) were collected from bloodstream infections in 2018-2019. Broth microdilution antimicrobial susceptibility testing was performed, and results were interpreted by US FDA, Clinical and Laboratory Standards Institute, and European Committee on Antimicrobial Susceptibility Testing guidelines. Genome sequencing was performed to determine multi-locus sequence, clonal complex (CC), spa, and SCCmec types; typing results were used to determine clonal group.

Overall, 97.3% of isolates were ceftobiprole susceptible by FDA and European Committee on Antimicrobial Susceptibility Testing criteria compared to 85.3% for ceftaroline, 73.3%-74.0% for clindamycin, 94.7% for trimethoprim-sulfamethoxazole, and 100.0% for linezolid, vancomycin, and daptomycin. More than 90% of isolates were CC5, CC8, or CC22, and ceftobiprole inhibited 97.7%, 98.3%, and 94.1% of these isolates, respectively, compared to 84.1%, 91.5%, and 70.6% activity of ceftaroline. Only 4 (2.7%) ceftobiprole non-susceptible isolates were identified compared to 22 (14.7%) non-susceptible to ceftaroline; all non-susceptible isolates were from clonal groups within CC8 (USA500 (Lyon) and Hungarian/Brazilian), CC5 (USA100 (Swiss) and USA100), or CC22 (UK-EMRSA-15).

Ceftobiprole demonstrated higher activity than ceftaroline against a phylogenetically diverse set of MRSA isolates and may represent a preferred broad-spectrum antimicrobial choice for the treatment of MRSA infections.