ArticleThe Journal of antimicrobial chemotherapy2023
In vivo pharmacokinetic/pharmacodynamic evaluation of cefepime/taniborbactam combination against cefepime-non-susceptible Enterobacterales and Pseudomonas aeruginosa in a murine pneumonia model.
Article in The Journal of antimicrobial chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
- Cefepime 2.0: Upgrading β-Lactamase Inhibitor Use.Microorganisms · 2026Review
- Preclinical Pharmacokinetics and Pharmacodynamics of Antibiotic Adjuvants.ACS infectious diseases · 2026Review
- 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
- Article
- Establishing the reference broth microdilution MIC method for cefepime-taniborbactam.Journal of clinical microbiology · 2025Article
- Plasma and intrapulmonary pharmacokinetics of cefepime and taniborbactam in healthy adult participants.Antimicrobial agents and chemotherapy · 2025Article
- β-Lactam/β-Lactamase Inhibitor Combination Antibiotics Under Development.Pathogens (Basel, Switzerland) · 2025Review
- Pharmacokinetic/pharmacodynamic analysis of sulbactam againstJAC-antimicrobial resistance · 2024Article
- Review
- New Agents Are Coming, and So Is the Resistance.Antibiotics (Basel, Switzerland) · 2024Review
- Aerosolized delivery of ESKAPE pathogens for murine pneumonia models.Scientific reports · 2024Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCefepime/taniborbactam is a cephalosporin/bicyclic boronate β-lactamase inhibitor combination in clinical development for nosocomial pneumonia due to MDR Gram-negative bacteria. A murine pneumonia model was used to characterize cefepime/taniborbactam in vivo pharmacodynamics against Enterobacterales and Pseudomonas aeruginosa strains.
methodsClinical cefepime-non-susceptible Enterobacterales and P. aeruginosa strains expressing serine carbapenemases and/or other cefepime-hydrolysing β-lactamases with cefepime/taniborbactam combination MICs of 0.12-16 mg/L were used. Cefepime and taniborbactam human-simulated regimens equivalent to clinical doses (i.e. 2/0.5 g q8h) were established in the pneumonia model. The in vivo activity of the cefepime human-simulated regimen given alone or concomitantly with escalating taniborbactam exposures against eight Enterobacterales and four P. aeruginosa strains was assessed. Taniborbactam pharmacokinetics were evaluated to determine systemic exposures of regimens used; taniborbactam fAUC0-24/MIC values required for efficacy were estimated using the Hill equation. In addition, the in vivo activity of the cefepime/taniborbactam combination human-simulated regimen was assessed against 18 strains.
resultsAmong Enterobacterales, median taniborbactam fAUC0-24/MIC values associated with stasis and 1 log kill were 0.96 and 4.03, respectively, while for P. aeruginosa, requirements were 1.35 and 3.02 for stasis and 1 log kill, respectively. The cefepime/taniborbactam human-simulated regimen produced >2 log kill in 14/18 strains and >1 log kill in 18/18 strains.
conclusionsCefepime/taniborbactam produced marked in vivo bactericidal activity against cefepime-non-susceptible Enterobacterales and P. aeruginosa isolates with cefepime/taniborbactam MICs up to and including 16 mg/L in the pneumonia model. Assessments of the probability of clinical attainment of the identified targets should be undertaken to support the selected cefepime/taniborbactam dose for treatment of nosocomial pneumonia.
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