1710. In Vitro Activity of Cefepime-Taniborbactam and Comparators Against a Global Collection of Carbapenem-Resistant Enterobacterales and Carbapenem-Resistant Pseudomonas aeruginosa With and Without Carbapenemases

Abstract

Abstract Background Carbapenem-resistant Enterobacterales (CRE) and P. aeruginosa (CRPA) present treatment difficulties owing to numerous possible resistance mechanisms, including the carriage of carbapenemases. Taniborbactam is a novel cyclic boronate-based broad-spectrum β-lactamase inhibitor with activity against serine-, and NDM & VIM metallo-β-lactamases (Ambler Classes A, B, C and D). The activity of the investigational combination cefepime-taniborbactam (FTB) and comparator agents was evaluated against a recent global collection of carbapenemase and non-carbapenemase producing CRE and CRPA. Methods 13,731 Enterobacterales and 4,619 P. aeruginosa isolates collected from 56 countries in 2018-2020 were a part of this study. MICs of cefepime with taniborbactam fixed at 4 µg/mL and comparators were determined according to CLSI guidelines and interpreted using 2022 CLSI breakpoints. CRE and CRPA were defined by resistance to meropenem. Organisms with FTB MIC ≥16 µg/mL were characterized by whole genome sequencing, while those resistant to meropenem were screened for acquired β-lactamase carriage by multiplex PCR followed by Sanger sequencing. Results Among the 637 CRE identified, 596 were found to carry a carbapenemase while the remaining 41 did not. For the carbapenemase-positive CRE, 89.8% and 94.5% of isolates were inhibited at ≤8 µg/mL and ≤16 µg/mL FTB, respectively, both values significantly greater than comparators (Table). For carbapenemase-negative CRE, 92.7% of isolates were inhibited at ≤8 µg/mL FTB, and 95.1% were inhibited at ≤16 µg/mL, again higher %s than comparators. Against carbapenemase-negative CRPA (n=703), FTB was the most active agent among the comparators, with 82.6% inhibited at ≤8 µg/mL and 94.9% inhibited at ≤16 µg/mL. Versus CRPA carrying carbapenemases (n=245), 61.9% were inhibited at ≤8 µg/mL FTB and 72.5% were inhibited at ≤16 µg/mL FTB. Conclusion FTB displayed substantial in vitro activity against CRE and CRPA regardless of whether they harbored carbapenemases. More isolates of each group were inhibited by FTB at ≤8 µg/mL than were susceptible to all tested β-lactam/β-lactamase inhibitor combinations. These data support the continued development of FTB as a potential new therapeutic antibacterial agent. Disclosures All Authors: No reported disclosures.