ArticleThe Journal of antimicrobial chemotherapy2018
Pharmacokinetics/pharmacodynamics of systemically administered polymyxin B against Klebsiella pneumoniae in mouse thigh and lung infection models.
Article in The Journal of antimicrobial chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.
- Guideline
- Personalizing Polymyxin B Dosing Using an Adaptive Feedback Control Algorithm.Antimicrobial agents and chemotherapy · 2018Pooled it
- Physiologically Based Pharmacokinetic Modeling of Inhaled Polymyxin B: From Rabbit Optimization to Human Predictions.Pharmaceutical research · 2026Article
- 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
- Pharmacodynamic evaluation of BRII-693, a next-generation synthetic macrocyclic peptide antibiotic, in the neutropenic mouse thigh and lung infection models against gram-negative pathogens.Antimicrobial agents and chemotherapy · 2026Article
- The pharmacodynamics of polymyxin B in Acinetobacter baumannii in murine thigh and lung infection models.The Journal of antimicrobial chemotherapy · 2026Article
- 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
- Physiologically-based pharmacokinetic model to predict loading dose polymyxin B exposure in critically ill patients with sepsis.Frontiers in pharmacology · 2026Article
- Safety and Efficacy of Nebulized Inhalation of Polymyxin B Sulfate for Carbapenem-Resistant Gram-Negative Bacterial Pneumonia: A Multi-Center, Prospective, Observational Study.Infection and drug resistance · 2026Article
- In Vitro and In Silico Evaluation of Polymyxin B Aerosol Delivery in Adult Mechanical Ventilation.Pharmaceutics · 2025Article
- Neutrophil-mediated delivery of hybrid cross-species nanovesicles for treatment of bacterial infections.Nature communications · 2025Article
- Chronic behavioral and seizure outcomes following experimental traumatic brain injury and comorbid Klebsiella pneumoniae lung infection in mice.Epilepsia · 2025Article
- Outcomes of carbapenem-resistant Acinetobacter baumannii bloodstream infections in intensive care units and prognostic effect of different antimicrobial regimens.Annals of intensive care · 2025Article
- Turning the Tide Against Carbapenem-resistantOpen forum infectious diseases · 2025Article
- Population Pharmacokinetic/Toxicodynamic Model for Polymyxin B in Critically Ill Patients to Identify the Risk of Nephrotoxicity.Clinical pharmacology and therapeutics · 2025Observational
- The relationship between the alveolar epithelial lining fluid concentration of intravenous plus inhaled polymyxin B and clinical efficacy in patients with pneumonia caused by carbapenem-resistant gram-negative bacilli: a prospective cohort study.BMC infectious diseases · 2025Article
- A Synthetic Phage-Peptide Conjugate as a Potent Antibacterial Agent forACS central science · 2025Article
- Review
- Harnessing endogenous anti-glycan antibodies using a novel, bifunctional immunotherapy to treat gram-negative bacterial infections.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Population pharmacokinetics of colistin sulfate in critically ill patients based on NONMEM.Scientific reports · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Background: The pharmacokinetic/pharmacodynamic (PK/PD) relationship for polymyxin B against Klebsiella pneumoniae infections is not known. Methods: Dose-fractionation studies with subcutaneous polymyxin B were conducted in neutropenic mice in which infection with three strains of K. pneumoniae had been produced in thighs or lungs. Dosing (thigh infection 0.5-120 mg/kg/day; lung infection 5-120 mg/kg/day) commenced 2 h after inoculation, and bacterial burden was measured 24 h later. Plasma exposure measures for unbound polymyxin B were from population pharmacokinetic analysis of single doses and plasma protein binding by ultracentrifugation. The inhibitory sigmoid dose-effect model was employed to determine the relationship between exposure and efficacy. Antibacterial activities of polymyxin B and colistin against thigh infection were compared at equimolar doses generating exposures resulting in maximal antibacterial activity. Results: The pharmacokinetics of polymyxin B were well described by a model comprising parallel linear and saturable pathways for absorption and elimination. Plasma binding of polymyxin B was constant (P > 0.05) over the range ∼0.9-37 mg/L; average (±SD) percentage bound was 91.4 ± 1.65. In thigh infection, antibacterial effect was well correlated with fAUC/MIC (R2 = 0.89). Target values of fAUC/MIC for stasis and 1 log10 kill were 1.22-13.5 and 3.72-28.0, respectively; 2 log10 kill was not achieved for any strain, even at the highest tolerated dose. There was no difference (P > 0.05) in antibacterial activity between polymyxin B and colistin with equimolar doses. It was not possible to achieve stasis in lung infection, even at the highest dose tolerated by mice. Conclusions: The results will assist in the design of optimized dosage regimens of polymyxin B.
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Registered trials
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.