ArticleThe Journal of antimicrobial chemotherapy2026
Pharmacodynamic studies of taniborbactam (VNRX-5133) combined with cefepime against β-lactamase-producing Gram-negative bacteria in a neutropenic murine thigh infection model.
Article in The Journal of antimicrobial chemotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Pharmacokinetics/pharmacodynamics of KSP-1007 in combination with meropenem against carbapenemase-producing gram-negative bacteria in a neutropenic murine thigh infection model.Antimicrobial agents and chemotherapy · 2026Article
- Cefepime Combined with Late-Generation β-Lactamase Inhibitors: Mechanisms of Action, In Vitro Activity, PK/PD Characteristics, Clinical Evidence and Resistance Mechanisms.Antibiotics (Basel, Switzerland) · 2026Review
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7 authors.
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Abstract
backgroundTaniborbactam (VNRX-5133) is a novel boronate-based β-lactamase inhibitor that directly inhibits all four classes of β-lactamases. We studied the pharmacodynamics of taniborbactam in combination with cefepime against β-lactamase-producing Enterobacterales and Pseudomonas aeruginosa.
methodsIn vitro, cefepime/taniborbactam combination was assessed with a checkerboard broth microdilution method against two ESBL-producing Enterobacterales and one AmpC- and one VIM-producing P. aeruginosa isolates (cefepime MIC 16-256 mg/L). In vivo, neutropenic infected mice were treated with cefepime, every 2 h for 24 h, alone or in combination with taniborbactam at q2h, q4h and q8h dosing intervals. Single dose escalation and dose-fractionation experiments were conducted in order to describe plasma pharmacokinetics and pharmacodynamics of taniborbactam, respectively.
resultsIn vitro, reversal of phenotypic resistance to cefepime was found at taniborbactam ≤0.03 and 0.25 mg/L for ESBL-producing E. coli and K. pneumoniae, and at 0.125 and 2 mg/L for VIM- and AmpC constitutively-producing P. aeruginosa, respectively. In vivo, cefepime alone marginally reached stasis against Enterobacterales and AmpC-producing P. aeruginosa. Taniborbactam restored cefepime's static effect against all isolates and its 1 log10 kill effect against all strains except the K. pneumoniae isolate. The percentage of time above free concentration threshold (%fT > Ct) best described taniborbactam efficacy (R2 = 0.50-0.80). At high cefepime exposures, area under the free concentration-time curve (fAUC) performed equally well (R2 0.49-0.70). A 40%-50% and 60%-100% fT > Ct of taniborbactam was associated with stasis and 1 log10 kill, respectively, at taniborbactam concentrations where reversal of cefepime resistance was found in vitro.
conclusionsTaniborbactam restored cefepime's activity against resistant Gram-negative bacteria in a time- and concentration-dependent manner at low and higher cefepime exposures, respectively.
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