ArticleAntimicrobial agents and chemotherapy2016
Colistin and Polymyxin B Dosage Regimens against Acinetobacter baumannii: Differences in Activity and the Emergence of Resistance.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 78 citations in OpenAlex.
- Effects of Different Component Contents of Colistin Methanesulfonate on the Pharmacokinetics of Prodrug and Formed Colistin in Human.Pharmaceutical research · 2021Trial
- Immunoassay for Colistin Monitoring in Critically Ill Patients Receiving Colistin Methanesulfonate Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Article
- 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
- Clinical outcomes and pharmacokinetics/pharmacodynamics of intravenous polymyxin B treatment for various site carbapenem-resistant gram-negative bacterial infections: a prospective observational multicenter study.Antimicrobial agents and chemotherapy · 2025Observational
- The First Report ofMicroorganisms · 2024Article
- Inhibition of the ATP synthase increases sensitivity of Escherichia coli carrying mcr-1 to polymyxin B.The Journal of antibiotics · 2024Article
- Individual Components of Polymyxin B Modeled via Population Pharmacokinetics to Design Humanized Dosage Regimens for a Bloodstream and Lung Infection Model in Immune-Competent Mice.Antimicrobial agents and chemotherapy · 2023Article
- Investigation of Peptidoglycan-Associated Lipoprotein ofInfection and immunity · 2023Article
- Effects of amikacin, polymyxin-B, and sulbactam combination on the pharmacodynamic indices of mutant selection against multi-drug resistantFrontiers in microbiology · 2022Article
- Carbapenem-resistantFrontiers in microbiology · 2022Review
- Predicting Antimicrobial Activity at the Target Site: Pharmacokinetic/Pharmacodynamic Indices versus Time-Kill Approaches.Antibiotics (Basel, Switzerland) · 2021Review
- Article
- Population Pharmacokinetics of Colistin Methanesulfonate Sodium and Colistin in Critically Ill Patients: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- BonA frommBio · 2021Article
- Rescuing the Last-Line Polymyxins: Achievements and Challenges.Pharmacological reviews · 2021Review
- Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting-Focus on ICU Patients and Gram-Negative Strains.Antibiotics (Basel, Switzerland) · 2020Review
- Antibiotic Activity of Wickerhamomyces anomalus Mycocins on Multidrug-Resistant Acinetobacter baumannii.Microbial ecology · 2020Article
- In Vitro Evaluation of Antimicrobial Peptide Tridecaptin M in Combination with Other Antibiotics against Multidrug ResistantMolecules (Basel, Switzerland) · 2020Article
- Polymyxin resistance in Klebsiella pneumoniae: multifaceted mechanisms utilized in the presence and absence of the plasmid-encoded phosphoethanolamine transferase gene mcr-1.The Journal of antimicrobial chemotherapy · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Infections caused by multidrug-resistant Acinetobacter baumannii are a major public health problem, and polymyxins are often the last line of therapy for recalcitrant infections by such isolates. The pharmacokinetics of the two clinically used polymyxins, polymyxin B and colistin, differ considerably, since colistin is administered as an inactive prodrug that undergoes slow conversion to colistin. However, the impact of these substantial pharmacokinetic differences on bacterial killing and resistance emergence is poorly understood. We assessed clinically relevant polymyxin B and colistin dosage regimens against one reference and three clinical A. baumannii strains in a dynamic one-compartment in vitro model. A new mechanism-based pharmacodynamic model was developed to describe and predict the drug concentrations and viable counts of the total and resistant populations. Rapid attainment of target concentrations was shown to be critical for polymyxin-induced bacterial killing. All polymyxin B regimens achieved peak concentrations of at least 1 mg/liter within 1 h and caused ≥4 log10 killing at 1 h. In contrast, the slow rise of colistin concentrations to 3 mg/liter over 48 h resulted in markedly reduced bacterial killing. A significant (4 to 6 log10 CFU/ml) amplification of resistant bacterial populations was common to all dosage regimens. The developed mechanism-based model explained the observed bacterial killing, regrowth, and resistance. The model also implicated adaptive polymyxin resistance as a key driver of bacterial regrowth and predicted the amplification of preexisting, highly polymyxin-resistant bacterial populations following polymyxin treatment. Antibiotic combination therapies seem the most promising option for minimizing the emergence of polymyxin resistance.
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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.