ArticleAntimicrobial agents and chemotherapy2016
Paradoxical Effect of Polymyxin B: High Drug Exposure Amplifies Resistance in Acinetobacter baumannii.
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 32 papers, 1 of them a synthesis that pooled it.
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- Guideline
- Resensitizing the Untreatable: Zidovudine and Polymyxin Combinations to Combat Pan-Drug-ResistantPharmaceuticals (Basel, Switzerland) · 2025Article
- Combatting mobile colistin-resistant (MCR), metallo-β-lactamase (MBL)-producingJAC-antimicrobial resistance · 2025Article
- Maximally precise combinations to overcome metallo-β-lactamase-producingAntimicrobial agents and chemotherapy · 2024Article
- Flavomycin restores colistin susceptibility in multidrug-resistant Gram-negative bacteria.mSystems · 2024Article
- Next generation antibiotic combinations to combat pan-drug resistant Klebsiella pneumoniae.Scientific reports · 2024Article
- Comprehensive analysis and novel insights into the efficacy of polymyxin B sulfate in the treatment of sepsis caused by carbapenem-resistant gram-negative bacteria.American journal of translational research · 2024Article
- Antimicrobial Pharmacokinetics and Pharmacodynamics in Critical Care: Adjusting the Dose in Extracorporeal Circulation and to Prevent the Genesis of Multiresistant Bacteria.Antibiotics (Basel, Switzerland) · 2023Review
- Mechanistic Insights to Combating NDM- and CTX-M-Coproducing Klebsiella pneumoniae by Targeting Cell Wall Synthesis and Outer Membrane Integrity.Antimicrobial agents and chemotherapy · 2022Article
- Bacterial Mixology: Combining Pharmacodynamic Models to Predict In Vitro Competition of MCR-1-HarboringAntibiotics (Basel, Switzerland) · 2021Article
- Assessing the predictive performance of population pharmacokinetic models for intravenous polymyxin B in critically ill patients.CPT: pharmacometrics & systems pharmacology · 2021Article
- Pharmacodynamic evaluation of suppression of in vitro resistance in Acinetobacter baumannii strains using polymyxin B-based combination therapy.Scientific reports · 2021Article
- Minocycline Alone and in Combination with Polymyxin B, Meropenem, and Sulbactam against Carbapenem-Susceptible and -Resistant Acinetobacter baumannii in anAntimicrobial agents and chemotherapy · 2021Article
- Colistin Update on Its Mechanism of Action and Resistance, Present and Future Challenges.Microorganisms · 2020Review
- 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
- Population Pharmacokinetics and Limited Sampling Strategy for Therapeutic Drug Monitoring of Polymyxin B in Chinese Patients With Multidrug-Resistant Gram-Negative Bacterial Infections.Frontiers in pharmacology · 2020Article
- Dose-Dependent Synergistic Interactions of Colistin with Rifampin, Meropenem, and Tigecycline against Carbapenem-Resistant Klebsiella pneumoniae Biofilms.Antimicrobial agents and chemotherapy · 2019Article
- Article
- Interplay of Klebsiella pneumoniaemSphere · 2018Article
- Polymyxin B and fosfomycin thwart KPC-producing Klebsiella pneumoniae in the hollow-fibre infection model.International journal of antimicrobial agents · 2018Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Administering polymyxin antibiotics in a traditional fashion may be ineffective against Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Here, we explored increasing the dose intensity of polymyxin B against two strains of Acinetobacter baumannii in the hollow-fiber infection model. The following dosage regimens were simulated for polymyxin B (t1/2 = 8 h): non-loading dose (1.43 mg/kg of body weight every 12 h [q12h]), loading dose (2.22 mg/kg q12h for 1 dose and then 1.43 mg/kg q12h), front-loading dose (3.33 mg/kg q12h for 1 dose followed by 1.43 mg/kg q12h), burst (5.53 mg/kg for 1 dose), and supraburst (18.4 mg/kg for 1 dose). Against both A. baumannii isolates, a rapid initial decline in the total population was observed within the first 6 h of polymyxin exposure, whereby greater polymyxin B exposure resulted in greater maximal killing of -1.25, -1.43, -2.84, -2.84, and -3.40 log10 CFU/ml within the first 6 h. Unexpectedly, we observed a paradoxical effect whereby higher polymyxin B exposures dramatically increased resistant subpopulations that grew on agar containing up to 10 mg/liter of polymyxin B over 336 h. High drug exposure also proliferated polymyxin-dependent growth. A cost-benefit pharmacokinetic/pharmacodynamic relationship between 24-h killing and 336-h resistance was explored. The intersecting point, where the benefit of bacterial killing was equal to the cost of resistance, was an fAUC0-24 (area under the concentration-time curve from 0 to 24 h for the free, unbound fraction of drug) of 38.5 mg · h/liter for polymyxin B. Increasing the dose intensity of polymyxin B resulted in amplification of resistance, highlighting the need to utilize polymyxins as part of a combination against high-bacterial-density A. baumannii infections.
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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.