Cefepime–taniborbactam activity against antimicrobial-resistant clinical isolates of Enterobacterales and Pseudomonas aeruginosa: GEARS global surveillance programme 2018–22

Abstract Objectives Taniborbactam is a boronate-based β-lactamase inhibitor in clinical development in combination with cefepime. Methods Cefepime–taniborbactam and comparator broth microdilution MICs were determined for patient isolates of Enterobacterales (n = 20 725) and Pseudomonas aeruginosa (n = 7919) collected in 59 countries from 2018 to 2022. Taniborbactam was tested at a fixed concentration of 4 mg/L. Isolates with cefepime–taniborbactam MICs ≥ 16 mg/L underwent WGS. β-Lactamase genes were identified in additional meropenem-resistant isolates by PCR/Sanger sequencing. Results Taniborbactam reduced the cefepime MIC90 value for all Enterobacterales from 16 to 0.25 mg/L (64-fold). At ≤16 mg/L, cefepime–taniborbactam inhibited 99.5% of all Enterobacterales isolates; 95% of isolates with MDR and ceftolozane–tazobactam-resistant phenotypes; ≥ 89% of isolates with meropenem-resistant and difficult-to-treat-resistant (DTR) phenotypes; 80% of isolates with meropenem–vaborbactam-resistant and ceftazidime–avibactam-resistant phenotypes; 100% of KPC-positive, 99% of OXA-48-like-positive, 99% of ESBL-positive, 97% of acquired AmpC-positive, 95% of VIM-positive and 76% of NDM-positive isolates. Against P. aeruginosa, taniborbactam reduced the cefepime MIC90 value from 32 to 8 mg/L (4-fold). At ≤16 mg/L, cefepime–taniborbactam inhibited 96.5% of all P. aeruginosa isolates; 85% of meropenem-resistant phenotype isolates; 80% of isolates with MDR and meropenem–vaborbactam-resistant phenotypes; 70% of isolates with DTR, ceftazidime–avibactam-resistant and ceftolozane–tazobactam-resistant phenotypes; and 82% of VIM-positive isolates. Multiple potential mechanisms of resistance, including carriage of IMP, or alterations in PBP3 (ftsI), porins (decreased permeability) and efflux (up-regulation) were present in most isolates with cefepime–taniborbactam MICs ≥ 16 mg/L. Conclusions Cefepime–taniborbactam exhibited potent in vitro activity against Enterobacterales and P. aeruginosa, and inhibited most carbapenem-resistant isolates, including those carrying serine carbapenemases or NDM/VIM MBLs.