ArticleThe Journal of antimicrobial chemotherapy2023
Imipenem/funobactam (formerly XNW4107) in vivo pharmacodynamics against serine carbapenemase-producing Gram-negative bacteria: a novel modelling approach for time-dependent killing.
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 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Population pharmacokinetics of imipenem in different populations for individualized dosing: a systematic review.Frontiers in pharmacology · 2025Pooled it
- Impact of renal impairment on pharmacokinetics, safety, and tolerability of funobactam, combined with imipenem and cilastatin.Antimicrobial agents and chemotherapy · 2026Article
- Plasma and intrapulmonary pharmacokinetics of funobactam, a novel diazabicyclooctane β-lactamase inhibitor, administered in combination with imipenem/cilastatin in healthy subjects.Antimicrobial agents and chemotherapy · 2026Article
- In Vitro Activity of Imipenem-Funobactam Against Clinical Isolates of Gram-Negative Bacilli.Antibiotics (Basel, Switzerland) · 2026Article
- Preclinical Pharmacokinetics and Pharmacodynamics of Antibiotic Adjuvants.ACS infectious diseases · 2026Review
- Clinically Significant Carbapenemases in Gram-Negative Pathogens: Molecular Diversity and Advances in β-Lactamase Inhibitor Therapy.Antibiotics (Basel, Switzerland) · 2026Review
- Membrane-Focused Strategies AgainstAntibiotics (Basel, Switzerland) · 2026Review
- Epidemiology of ESBL-Producing, Carbapenem-Resistant, and Carbapenemase-Producing Enterobacterales in Southern Africa.Antibiotics (Basel, Switzerland) · 2026Review
- Current and future options for the treatment of serious infections due to carbapenem-resistantClinical microbiology reviews · 2025Review
- Challenges of Carbapenem-ResistantAntibiotics (Basel, Switzerland) · 2025Review
- Article
- Review
- Unveiling the Secrets ofInternational journal of molecular sciences · 2024Review
- Role of β-Lactamase Inhibitors as Potentiators in Antimicrobial Chemotherapy Targeting Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImipenem/funobactam (formerly XNW4107) is a novel β-lactam/β-lactamase inhibitor with activity against MDR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales strains. Using a neutropenic murine thigh infection model, we aimed to determine the pharmacokinetic/pharmacodynamic (PK/PD) index, relative to funobactam exposure, that correlated most closely with the in vivo efficacy of imipenem/funobactam combination and the magnitude of index required for efficacy against serine carbapenemase-producing clinical strains.
methodsDose-fractionation was conducted against three strains. Imipenem human-simulated regimen (HSR, 500 mg q6h 1 h infusion) efficacy in combination with escalating funobactam exposures against seven A. baumannii, four P. aeruginosa and four Klebsiella pneumoniae (imipenem/funobactam MICs 0.25-16 mg/L) was assessed as 24 h change in log10cfu/thigh.
resultsIncreased funobactam fractionation enhanced efficacy, indicating time-dependent killing. Changes in log10cfu/thigh versus %fT > MIC were poorly predictive of efficacy; bactericidal activity was observed at %fT > MIC = 0%. Across different threshold plasma funobactam concentrations (CTs), %fT > CT(1 mg/L) had the highest correlation with efficacy. Normalizing the %fT > CT = 1 mg/L index to the respective isolate imipenem/funobactam MIC ([%fT > CT]/MIC) allowed integration of the isolate's susceptibility, which further enhanced the correlation. Median (%fT > CT[1 mg/L])/MIC values associated with 1-log reductions were 9.82 and 9.90 for A. baumannii and P. aeruginosa, respectively. Median (%fT > CT[1 mg/L])/MIC associated with stasis was 55.73 for K. pneumoniae. Imipenem/funobactam 500/250 mg q6h 1 h infusion HSR produced >1-log kill against 6/7 A. baumannii, 4/4 P. aeruginosa and stasis against 4/4 K. pneumoniae.
conclusionsImipenem/funobactam showed potent in vivo efficacy against serine carbapenemase-producers. The novel PK/PD index (%fT > CT)/MIC appeared to best describe in vivo activity.
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