Ceftobiprole Activity When Tested Against Contemporary Bacteria Causing Bloodstream Infections in the US (2016)

BACKGROUND: Ceftobiprole medocaril (prodrug of ceftobiprole) is an advanced cephalosporin, approved for adults in multiple European countries for the treatment of hospital-acquired pneumonia (excluding ventilator-associated pneumonia) or community-acquired pneumonia. It is not approved in the US; however, it has achieved qualified infectious disease product status and two phase 3 studies supported by BARDA are planned to begin in the US in 2017. METHODS: A total of 2,787 Gram-positive (GP) and -negative (GN) isolates from bloodstream infections (BSI) from 30 medical centers in the SENTRY Antimicrobial Surveillance Program were evaluated. Isolates were collected in the US during 2016. Susceptibility (S) testing was performed by reference broth microdilution method against ceftobiprole and comparators. Isolates included 693 Staphylococcus aureus (SA), 216 coagulase-negative staphylococci (CoNS), 244 enterococci, 63 Streptococcus pneumoniae (SPN), 74 viridans group streptococci (VGS), 138 β-haemolytic streptococci (BHS), 1,105 Enterobacteriaceae (ENT), 129 Pseudomonas aeruginosa (PSA), 41 Acinetobacter spp. (ASP), 30 Stenotrophomonas maltophila, 19 Haemophilus spp. and 35 miscellaneous bacteria. RESULTS: Methicillin-resistant S. aureus (MRSA) S rates were lower than for methicillin-susceptible S. aureus (MSSA) for most agents. For levofloxacin (LEV) and erythromycin (ERY), the S rates were LEV: MRSA, 23.2%; MSSA, 86.1%; ERY: MRSA, 9.0%; MSSA, 69.3%. All MSSA and 99.0% of MRSA were S to ceftobiprole, while all MSSA and 96.5% of MRSA were S to ceftaroline (CPT). For CoNS, 98.1% of ceftobiprole MIC values were ≤2mg/L. Ceftobiprole was active against Enterococcus faecalis (96.1% ≤2mg/L) and not against E. faecium (18.9% ≤2mg/L). Against ENT, ceftobiprole (85.0%S) was similar in activity to ceftazidime (CAZ, 87.2%S) and cefepime (FEP, 88.9%S). The MIC(50/90) values for ceftobiprole, FEP, and CAZ against PSA were identical at 2/16 mg/L. CONCLUSION: Ceftobiprole exhibited potent in vitro activity against GP and GN isolates from contemporary BSI in the US. These results support further clinical evaluation of ceftobiprole for the treatment of BSI. DISCLOSURES: R. K. Flamm, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; L. R. Duncan, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; D. Shortridge, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; J. I. Smart, Basilea Pharmaceutica International Ltd.: Employee, Salary; K. Hamed, Basilea Pharmaceutica International Ltd.: Employee, Salary; R. E. Mendes, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; H. S. Sader, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant