In vitro comparative activity of the new beta-lactamase inhibitor taniborbactam with cefepime and meropenem against Klebsiella pneumoniae and cefepime against Pseudomonas aeruginosa metallo-beta-lactamase producing clinical isolates.

Metallo-beta-lactamase (MBL)-producing gram-negative bacteria are increasing worldwide with very few agents being active against these pathogens. Taniborbactam (formerly VNRX-5133) is a newly developed bicyclic boronate beta-lactamase inhibitor which directly inhibits all four Ambler classes of beta-lactamases. In the present study the in vitro activity of cefepime and meropenem combined with taniborbactam against 100 Klebsiella pneumoniae and cefepime combined with taniborbactam against 100 Pseudomonas aeruginosa molecularly characterized MBL-producing strains were investigated using ISO standard broth microdilution assays in comparison with a panel of antimicrobial agents that are used in clinical practice (amikacin, aztreonam, ciprofloxacin, levofloxacin, gentamicin, piperacillin/tazobactam, imipenem, tigecycline, ceftolozane-tazobactam, cefepime-tazobactam, meropenem-vaborbactam, ceftazidime-avibactam). For K. pneumoniae isolates, the MIC90s were ≥64 mg/l for all drugs except cefepime-taniborbactam (16 mg/l; 87% inhibited at ≤8/4 mg/l), meropenem-taniborbactam (4 mg/l; 94% inhibited at ≤8/4 mg/l) and tigecycline (8 mg/l) with high levels of resistance (≥65%) found for all approved comparator antimicrobials tested. For P. aeruginosa, the MIC90s were ≥64 mg/l for all drugs except aztreonam (32 mg/l), cefepime-taniborbactam (32 mg/l; 88% inhibited at ≤16/4 mg/l) and ciprofloxacin (32 mg/l) with high levels of resistance (≥73%) for all approved drugs except aztreonam (27%). Taniborbactam reduced cefepime and meropenem MICs by a median 5 and 7 two-fold dilutions to ≤8 mg/l in 87% and 94% of MBL-producing K. pneumoniae isolates, and cefepime MICs by a median 5 two-fold dilutions to ≤16 mg/l in 86% of MBL-producing P. aeruginosa, respectively. The combinations cefepime-taniborbactam and meropenem-taniborbactam could be promising alternatives for treatment options for infections by MBL producing isolates.