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
blaOXA-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 (
blaOXA-48
,
blaCTX-M-15
,
blaTEM-1
, and
blaOXA-1
) and MLI (
blaOXA-48
,
blaVEB
,
blaTEM-1
, and
blaCMY-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
blaOXA-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.