ArticleThe Journal of antimicrobial chemotherapy2023
Pharmacokinetic and pharmacodynamic properties of polymyxin B in Escherichia coli and Klebsiella pneumoniae murine infection models.
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, 9 citations in OpenAlex.
- Designing the Next Generation of Antibiotics: Structure, SAR, and Strategy in Medicinal Chemistry (2000-2025).Medicinal research reviews · 2026Review
- Polymyxin B Intravenous Administration Strategy Guided by Minimum Inhibitory Concentration in Critically Ill Patients With Pulmonary Infection: Insights From PBPK Modeling.CPT: pharmacometrics & systems pharmacology · 2026Article
- OPTIMIS: Optimizing Personalized Therapies through Integrated Multiscale Intelligent Simulation.bioRxiv : the preprint server for biology · 2026Article
- The pharmacodynamics of polymyxin B in Acinetobacter baumannii in murine thigh and lung infection models.The Journal of antimicrobial chemotherapy · 2026Article
- From Laboratory to Clinic: Translational Medicine Paradigm of Polymyxin B Nanopreparations for Overcoming Drug-Resistant Bacterial Infections.International journal of nanomedicine · 2026Review
- Can the two-point method based on peak and trough concentrations accurately estimate the area under the curve of polymyxin B? A Monte Carlo simulation study.Frontiers in pharmacology · 2026Article
- Comparative study on the wound healing effects of local versus systemic application of Polymyxin B in mice infected with multidrug-resistantFrontiers in microbiology · 2026Article
- Polymyxin resistance in Gram-negative bacteria: a comprehensive review with a focus on the role of 4-amino-4-doexy-L-arabinose.Molecular biology reports · 2025Review
- The synergistic effect of the combination of polymyxin B and rifampicin in a murine neutropenic thigh infection model with E. coli and K. pneumoniae.The Journal of antimicrobial chemotherapy · 2025Article
- Simulation-based evaluation of the impact of dose fractionation study design on antibiotic PKPD analyses.JAC-antimicrobial resistance · 2025Article
- Article
- Assessing Clinical Potential of Old Antibiotics against Severe Infections by Multi-Drug-Resistant Gram-Negative Bacteria Using In Silico Modelling.Pharmaceuticals (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough polymyxin B has been in use since the late 1950s, there have been limited studies done to unravel its pharmacokinetics (PK) and pharmacodynamics (PD) index.
methodsWe determined, in neutropenic infected mice, the PK, plasma protein binding and PK/PD index best correlating with efficacy for Escherichia coli and Klebsiella pneumoniae strains.
resultsThe pharmacokinetic profile showed non-linear PK; dose was significantly correlated with absorption rate and clearance. The inhibitory sigmoid dose-effect model for the fCmax/MIC index of E. coli fitted best, but was only modestly higher than the R2 of %fT>MIC and fAUC/MIC (R2 0.91-0.93). For K. pneumoniae the fAUC/MIC index had the best fit, which was slightly higher than the R2 of %fT>MIC and fCmax/MIC (R2 0.85-0.91). Static targets of polymyxin B fAUC/MIC were 27.5-102.6 (median 63.5) and 5.9-60.5 (median 11.6) in E. coli and in K. pneumoniae isolates, respectively. A 1 log kill effect was only reached in two E. coli isolates and one K. pneumoniae. The PTA with the standard dosing was low for isolates with MIC >0.25 mg/L.
conclusionsThis study confirms that fAUC/MIC can describe the exposure-response relationship for polymyxin B. The 1 log kill effect was achieved in the minority of the isolates whereas polymyxin B PK/PD targets cannot be attained for the majority of clinical isolates with the standard dosing regimen, indicating that polymyxin B may be not effective against serious infections as monotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.