ArticleThe Journal of antimicrobial chemotherapy2022
Clinical exposure-response relationship of cefepime/taniborbactam against Gram-negative organisms in the murine complicated urinary tract infection model.
Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Bronchopulmonary disposition of IV cefepime/taniborbactam (2-0.5 g) administered over 2 h in healthy adult subjects.The Journal of antimicrobial chemotherapy · 2023Trial
- 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
- Real-World Evidence and Multidrug Resistant Infections: How Can We Leverage RWE to Improve Patient Outcome with the Novel Beta-Lactam and Beta-Lactam/Beta-Lactamase Inhibitor Combinations.Infection and drug resistance · 2026Review
- Article
- Article
- Assessment of human exposures of cefepime-taniborbactam against cefepime-resistant Enterobacterales andAntimicrobial agents and chemotherapy · 2025Article
- β-Lactam/β-Lactamase Inhibitor Combination Antibiotics Under Development.Pathogens (Basel, Switzerland) · 2025Review
- Revitalizing cephalosporins: The promise of β-lactamase inhibitor combinations.GMS hygiene and infection control · 2025Article
- ARGONAUT-IV: susceptibility of carbapenemase-producingAntimicrobial agents and chemotherapy · 2024Article
- Review
- ARGONAUT-III and -V: susceptibility of carbapenem-resistantAntimicrobial agents and chemotherapy · 2024Article
- Antibiotic Therapy Strategies for Treating Gram-Negative Severe Infections in the Critically Ill: A Narrative Review.Antibiotics (Basel, Switzerland) · 2023Review
- Novel Antimicrobial Agents for Gram-Negative Pathogens.Antibiotics (Basel, Switzerland) · 2023Review
- In vivo pharmacokinetic/pharmacodynamic evaluation of cefepime/taniborbactam combination against cefepime-non-susceptible Enterobacterales and Pseudomonas aeruginosa in a murine pneumonia model.The Journal of antimicrobial chemotherapy · 2023Article
- Article
- Vancomycin-arginine (STM-001) abrogates ESBL carrier and carbapenem-resistant Escherichia coli burden in a murine complicated urinary tract infection model.The Journal of antimicrobial chemotherapy · 2022Article
- New Drugs for the Treatment ofAntibiotics (Basel, Switzerland) · 2022Review
- Microbiological, Clinical, and PK/PD Features of the New Anti-Gram-Negative Antibiotics: β-Lactam/β-Lactamase Inhibitors in Combination and Cefiderocol-An All-Inclusive Guide for Clinicians.Pharmaceuticals (Basel, Switzerland) · 2022Review
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Authors and funding
3 authors.
Funding
Abstract
objectivesComplicated urinary tract infections (cUTIs) are frequently encountered in hospitals and ICUs. Increasingly, the causative pathogens harbour enzymatic resistance mechanisms. Taniborbactam is a novel β-lactamase inhibitor with activity against Ambler class A, B, C and D β-lactamases. Herein, we assessed the efficacy of cefepime alone and the combination cefepime/taniborbactam in a neutropenic murine cUTI model.
methodsEighteen cefepime-resistant clinical isolates (9 Enterobacterales, 3 Pseudomonas aeruginosa and 6 Stenotrophomonas maltophilia; cefepime MIC = 32 to >512 mg/L) were assessed. Cefepime/taniborbactam MICs ranged from 0.06 to 128 mg/L. Human-simulated plasma regimens (HSRs) of cefepime alone and in combination with taniborbactam were developed in the murine cUTI model. The efficacy of cefepime HSR and cefepime/taniborbactam HSR was determined as the change in log10 cfu/kidney at 48 h compared with 48 h controls.
resultsMean ± SD initial bacterial burden was 5.66 ± 0.56 log10 cfu/kidney, which increased to 9.05 ± 0.39 log10 cfu/kidney at 48 h. The cefepime HSR was ineffective, as bacterial burden was similar to untreated controls (-0.14 ± 0.40 change in log10 cfu/kidney). In contrast, cefepime/taniborbactam exhibited substantial killing, with log10 cfu/kidney changes of -5.48 ± 1.3, -4.79 ± 0.3 and -5.04 ± 0.7 for ESBL/AmpC-, KPC- and OXA-48-harbouring Enterobacterales, respectively. Cefepime/taniborbactam also exhibited robust killing of P. aeruginosa (-6.5 ± 0.26) and S. maltophilia (-5.66 ± 0.71).
conclusionsHumanized exposures of cefepime/taniborbactam achieved robust killing of Enterobacterales, P. aeruginosa and S. maltophilia harbouring ESBL, AmpC, KPC and/or OXA-48. These data support the role of cefepime/taniborbactam for cUTI treatment for cefepime/taniborbactam MICs up to 32 mg/L.
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