Cefepime-taniborbactam demonstrates potent in vitro activity vs Enterobacterales with bla OXA-48

ABSTRACT Taniborbactam (formerly VNRX-5133) is a novel, investigational boronic acid β-lactamase inhibitor. The combination of cefepime (FEP) with taniborbactam is active against Enterobacterales carrying class A, B, C, and/or D enzymes. We assessed the activity of FEP-taniborbactam against Enterobacterales clinical strains carrying bla OXA-48 ( N = 50, 100%), of which 78% harbored at least one extended-spectrum β-lactamase (ESBL). CLSI-based agar dilution susceptibility testing was conducted using FEP-taniborbactam and comparators FEP, meropenem-vaborbactam (MVB), and ceftazidime-avibactam (CZA). The addition of taniborbactam lowered FEP MICs to the provisionally susceptible range of ≤16 µg/mL; the MIC 90 value decreased from ≥64 µg/mL for FEP to 4 µg/mL for FEP-taniborbactam. Notably, FEP-taniborbactam MIC 50 /MIC 90 values (0.5/4 µg/mL) were lower than those for MVB (1/16 µg/mL) and comparable to those for CZA (0.5/1 µg/mL). Time-kill assays with E. coli clinical strains DOV ( bla OXA-48 , bla CTX-M-15 , bla TEM-1 , and bla OXA-1 ) and MLI ( bla OXA-48 , bla VEB , bla TEM-1 , and bla CMY-2 ) revealed that FEP-taniborbactam at concentrations 1×, 2×, and 4× MIC displayed time-dependent reductions in the number of CFU/mL from 0 to 6 h, and at 4× MIC demonstrated bactericidal activity (3 log 10 reduction in CFU/mL at 24 h). Therefore, taniborbactam in combination with FEP was highly active against this diverse panel of Enterobacterales with bla OXA-48 and represents a potential addition to our antibiotic arsenal. IMPORTANCE OXA-48-like β-lactamases are class D carbapenemases widespread in Klebsiella pneumoniae and other Enterobacterales and are associated with carbapenem treatment failures. As up to 80% of OXA-48-like positive isolates coproduce extended-spectrum β-lactamases, a combination of β-lactams with broad-spectrum β-lactamase inhibitors is required to counteract all OXA-48-producing strains effectively. Herein, we evaluated the activity of cefepime-taniborbactam against 50 clinical strains producing OXA-48. We report that adding taniborbactam shifted the minimum inhibitory concentration (MIC) toward cefepime’s susceptible range, restoring its antimicrobial activity. Notably, cefepime-taniborbactam MIC 50 /MIC 90 values (0.5/4 µg/mL) were comparable to ceftazidime-avibactam (0.5/1 µg/mL). Finally, time-kill assays revealed sustained bactericidal activity of cefepime-taniborbactam for up to 24 h. In conclusion, cefepime-taniborbactam will be a welcome addition to the antibiotic arsenal to combat Enterobacterales producing OXA-48.