Inference of ceftobiprole susceptibility through surrogate testing of ceftaroline

Area of Science:

• Clinical microbiology
• Infectious diseases
• Antimicrobial resistance

Background:

• Ceftobiprole, an advanced-generation cephalosporin, is active against challenging pathogens like methicillin-resistant Staphylococcus aureus (MRSA).
• Ceftobiprole received US approval in April 2024, but commercial susceptibility testing systems are not yet available.
• There is an interim need for a reliable method to assess ceftobiprole susceptibility in clinical settings.

Purpose of the Study:

• To evaluate the accuracy of using ceftaroline susceptibility as a surrogate marker for predicting ceftobiprole susceptibility.
• To determine the error rates (minor and very major) associated with this surrogate testing strategy.
• To facilitate the rapid clinical adoption of ceftobiprole pending the availability of dedicated susceptibility testing.

Main Methods:

• Analysis of 42,363 clinical bacterial isolates collected from 34 US medical centers (2016-2020) via the SENTRY Antimicrobial Surveillance Program.
• Determination of minimum inhibitory concentrations (MICs) for ceftobiprole and ceftaroline using broth microdilution.
• Calculation of accuracy, minor error rate, and very major error rate for ceftaroline as a surrogate for ceftobiprole susceptibility.

Main Results:

• The accuracy of predicting ceftobiprole susceptibility using ceftaroline susceptibility exceeded 99% for key pathogens, including S. aureus (99.98%), MRSA (99.95%), E. coli (99.97%), and K. pneumoniae (99.91%).
• Accuracy was also high for Streptococcus pneumoniae (99.48%), beta-hemolytic streptococci (100.00%), Haemophilus spp. (98.86%), and Enterobacterales (98.73%).
• Minor error rates were consistently below 1%, and very major errors were infrequent, observed primarily in S. pneumoniae and Haemophilus spp.

Conclusions:

• Susceptibility to ceftobiprole can be reliably inferred from ceftaroline susceptibility testing with very high accuracy across a broad range of clinically significant bacteria.
• The use of ceftaroline susceptibility as a surrogate marker is a viable strategy to guide ceftobiprole therapy in the interim period before commercial ceftobiprole susceptibility tests become available.
• This approach supports the effective clinical utilization of newly approved ceftobiprole.