Activity of Cefepime in Combination with the Novel β-Lactamase Inhibitor Taniborbactam (VNRX-5133) against Extended-Spectrum-β-Lactamase-Producing Isolates in Checkerboard Assays.

Extended-spectrum-β-lactamase (ESBL)-producing strains are increasing worldwide, limiting therapeutic options. Taniborbactam (VNRX-5133) is a newly developed β-lactamase inhibitor with a wide spectrum of activity covering both serine and metallo enzymes. We therefore evaluated cefepime-taniborbactam activity against ESBL-producing isolates and determined the concentrations to be used in MIC determinations in the clinical laboratory. The activity of cefepime (0.06 to 256 mg liter) combined with taniborbactam (0.03 to 32 mg liter) against 129 clinically and molecularly well-documented ESBL-producing isolates (42 , 39 , 28 , 16 , 2 , and 2 ) was tested with a broth microdilution checkerboard method based on the ISO standard. The MICs of cefepime alone and in combination, together with percentage resistance at different concentrations of taniborbactam, were calculated for each species and resistance mechanism. The median (range)/MIC of cefepime was 32 (0.125 to 256)/256 mg liter for all isolates ( = 101), with 72% being resistant, and 32 (8 to 256)/128 mg liter for the 28 isolates, with 86% being resistant. The median (range)/90th percentile concentration of taniborbactam required to restore susceptibility to cefepime (MIC ≤1 mg liter) was 0.06 (≤0.03 to 32)/4 mg liter and susceptibility to increased exposure to cefepime (MIC ≤8 mg liter) 1 (≤0.032 to 32)/32 mg liter At a fixed concentration of 4 mg liter of taniborbactam, cefepime median (range)/MIC were reduced to 0.125 (0.06 to 4)/1 mg liter for with no resistant isolates found, and to 8 (2 to 64)/16 mg liter for isolates, where 36% remained resistant. The combination cefepime-taniborbactam demonstrated a potent activity against ESBL isolates, restoring susceptibility of all and two-thirds of isolates.