In vitro
activity of cefepime-taniborbactam against carbapenemase producing
Enterobacterales
and
Pseudomonas aeruginosa
isolates recovered in Spain
Novel β-lactam-β-lactamase inhibitor combinations currently approved for clinical use are poorly active against metallo-β-lactamase (MBL)-producing strains. We evaluated the in vitro activity of cefepime-taniborbactam (FTB, formerly cefepime/VNRX-5133) and comparator agents against carbapenemase-producing Enterobacterales (n=247) and carbapenem-resistant Pseudomonas spp. (n=170) clinical isolates prospectively collected from different clinical origin in patients admitted to 8 Spanish hospitals. FTB was the most active agent in both Enterobacterales (97.6% MIC FTB ≤8/4 mg/L) and Pseudomonas populations (67.1% MIC FTB ≤8/4 mg/L). MIC FTB was >8 mg/L in 6/247 (2.4%) Enterobacterales isolates (3 KPC- Klebsiella pneumoniae , 1 VIM- Enterobacter cloacae , 1 IMP- E. cloacae and 1 NDM- Escherichia coli ) and in 56/170 (32.9%) Pseudomonas spp., 19 of them carbapenemase producers (15 VIM, 2 GES, 1 GES+VIM, 1 GES+KPC). Against the Enterobacterales isolates with meropenem MIC>2 mg/L (138/247), FTB was the most active agent against both serine-β-lactamases (107/138) and MBL producers (31/138) (97.2% and 93.5% MIC FTB ≤8/4 mg/L, respectively) whereas the activity of comparators was reduced, particularly against the MBL producers (ceftazidime-avibactam, 94.4% and 12.9%; meropenem-vaborbactam, 85.0% and 64.5%; imipenem-relebactam, 76.6% and 9.7%; ceftolozane-tazobactam, 1.9% and 0%; piperacillin-tazobactam, 0% and 0%, respectively). Among the meropenem-resistant Pseudomonas spp. isolates (163/170, MIC>2 mg/L), activity of FTB against serine-β-lactamase (35/163) and MBL producers (43/163) was 88.6% and 65.1%, respectively, whereas the susceptibility of comparators was: ceftazidime-avibactam, 88.5% and 16.0%; meropenem-vaborbactam, 8.5% and 7.0%; imipenem-relebactam, 2.9% and 2.3%; ceftolozane-tazobactam, 0% and 2.3%; and piperacillin-tazobactam, 0% and 0%, respectively. Microbiological results suggest FTB as a potential therapeutic option in patients infected with carbapenemase-producing Enterobacterales and carbapenem-resistant Pseudomonas isolates, including MBL producers.