Inference of ceftobiprole susceptibility through surrogate testing of ceftaroline

Ceftobiprole is an advanced-generation cephalosporin active against methicillin-resistant Staphylococcus aureus and other clinically relevant bacteria. Ceftobiprole was recently (April 2024) approved for clinical use in the United States, but susceptibility testing is still not available on commercial automated susceptibility testing systems. We evaluated the accuracy and error rates when using susceptibility to ceftaroline to predict susceptibility to ceftobiprole. A total of 42,363 clinical isolates were collected through the SENTRY Antimicrobial Surveillance Program from 34 US medical centers in 2016-2020 and tested against ceftobiprole and ceftaroline by broth microdilution method. The accuracy of the surrogate test (susceptibility to ceftaroline) was defined as the percentage of isolates susceptible to ceftobiprole among ceftaroline-susceptible isolates. Minor error rate was then defined as the percentage of ceftobiprole-intermediate among ceftaroline-susceptible isolates, and very major error was defined as the percentage of ceftobiprole-resistant isolates among ceftaroline-susceptible isolates. The accuracy of the surrogate test to predict susceptibility to ceftobiprole was >99% for S. aureus (99.98%), including methicillin-resistant S. aureus (99.95%), Streptococcus pneumoniae (99.48%), β-hemolytic streptococci (100.00%), Escherichia coli (99.97%), and Klebsiella pneumoniae (99.91%). Accuracy was also extremely high for Haemophilus spp. (98.86%) and Enterobacterales (98.73%). Minor error rates were <1% for all organism groups evaluated, and very major errors were only observed with S. pneumoniae (0.06%), Haemophilus spp. (0.31%), Enterobacterales (0.40%), and K. pneumoniae (0.03%). In conclusion, the results of the comparative analyses of ceftobiprole and ceftaroline MIC values show that susceptibility to ceftobiprole can be inferred by susceptibility to ceftaroline with very high accuracy.

Ceftobiprole was recently (April 2024) approved for clinical use in the United States but susceptibility testing is still not available on commercial automated susceptibility testing systems and may not be available for some time. In the interim, one possible strategy to assess ceftobiprole susceptibility would be to apply the susceptibility results of ceftaroline as a surrogate marker of susceptibility. This strategy could facilitate rapid clinical use of ceftobiprole in the United States pending the more necessary availability of commercial susceptibility testing devices to direct testing ceftobiprole.