2173. Activity of Ceftobiprole Against Enterococcus faecalis Clinical Isolates From the United States (2016–2020), Including Those From Difficult-to-Treat Infections
Authors: Mendes Rodrigo E , Duncan Leonard R , Sader Helio S , Smart Jennifer , Jones Mark E , Castanheira Mariana 
Published: November 2023

Abstract

Background
Ceftobiprole (BPR) is an advanced-generation cephalosporin that has in vitro and in vivo activity against clinically important Gram-positive organisms, including MRSA and Gram-negative organisms. While BPR does not have clinically relevant activity against Enterococcus faecium, BPR is active against E. faecalis, an opportunistic bacterial pathogen of increasing clinical relevance and a significant cause of infective endocarditis. This study evaluated the activity of BPR and comparator agents against E. faecalis isolated from patients hospitalized in US medical centers.

Methods
A total of 1,834 E. faecalis isolated from 34 US medical centers (2016–2020) were included. Isolates collected were responsible for bloodstream infections (40.8%), urinary tract infections (23.4%), skin and skin structure infections (22.0%), and other infection types (13.9%), including bone and joint infections (BJI; 1.6%), diabetic foot infections (DFI; 0.9%), and endocarditis (END; 0.8%). Isolates were tested for susceptibility using the CLSI broth microdilution method and MIC interpretations followed CLSI criteria. For BPR, the PK/PD non–species-related breakpoint of ≤4 mg/L was used.

Results
BPR inhibited 99.3% of all E. faecalis at ≤4 mg/L, whereas the comparator agents, ampicillin (AMP), daptomycin (DAP), linezolid (LZD), and vancomycin (VAN), inhibited between 97.0% to 100% of all isolates at their respective breakpoints. A total of 3% of all E. faecalis isolates were VAN resistant. BPR had similar MIC90 results of 2 mg/L and 4 mg/L when tested against VAN-susceptible and -resistant isolates, respectively. AMP, DAP, and LZD were also active against VAN-susceptible and -resistant E. faecalis. All (100%) isolates causing difficult-to-treat infections, such as bone/joint and diabetic foot infections and infective endocarditis, were inhibited by BPR at ≤4 mg/L in addition to AMP, DAP, and LZD at their respective breakpoints.

Conclusion
These data suggest that BPR represents a potential option for empirical and guided treatment of infections caused by E. faecalis in US hospitals, including isolates causing difficult-to-treat infections.

Disclosures
Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Leonard R. Duncan, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Helio S. Sader, MD, PhD, FIDSA, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Jennifer Smart, PhD, Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds Mark E. Jones, PhD, Astellas Pharma Global Development, Inc: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support