Combination Cefepime-Taniborbactam (FTB) May Be a New Treatment Option for Resistant Infections

Formerly VNRX-5133, taniborbactam is a novel cyclic boronate-based broad-spectrum β-lactamase inhibitor with effective and selective direct inhibitory activity against both serine- and metallo-β-lactamases (Ambler Class A, B, C, and D).

When combined taniborbactam restores the activity of cefepime against difficult-to-treat infections, such as cephalosporin- and carbapenem-resistant Enterobacterales and Pseudomonas aeruginosa. In a recent study presented virtually at the annual IDWeek conference, investigators analyzed the activity of the investigational combination cefepime-taniborbactam (FTB) and comparator agents against clinical isolates of Enterobacterales.

Investigators combined MICs of cefepime and taniborbactam fixed at 4 µg/mL. They determined the comparator agents using CLSI M07-A11 guidelines against 10,543 Enterobacterales. The Enterobacterales isolates were collected from 259 sites in 56 countries during a 2018-2020 global surveillance study.

Investigators used PCR and sequencing to examine 827 isolates with meropenem MIC ≥4 µg/mL (n=421) or with cefepime and/or ceftazidime MIC ≥2 µg/mL (n=406) to detect for MBLs, KPC, ESBLs, and OXA-48 group genes. A total of 48 isolates with FTB MIC values ≥16 µg/mL were analyzed by WGS.

The investigators found a total of 23% isolates to be nonsusceptible (NS) to cefepime, and 15.9% to be NS to piperacillin-tazobactam (TZP). FTB had potent activity against all Enterobacterales, with MIC50/90 values of 0.06/0.25 µg/mL and 99.5% inhibited at ≤8 µg/mL. Among isolates with elevated FTB MICs, there were IMP-type enzymes, variations in the cefepime target (penicillin binding protein three), permeability defects combined with acquired β-lactamases, and/or potential up-regulated efflux.

The study results showed taniborbactam significantly restored in vitro activity of cefepime against Enterobacterales. Notably, this included isolates NS to recently approved BL/BLI combinations and expressing serine and metallo-β-lactamases. The investigators concluded by advocating for continued development of FTB to treat infections with resistant Gram-negative infections.