ArticleThe Journal of antimicrobial chemotherapy2017
Pharmacodynamics of dose-escalated 'front-loading' polymyxin B regimens against polymyxin-resistant mcr-1-harbouring Escherichia coli.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Guideline
- Combatting mobile colistin-resistant (MCR), metallo-β-lactamase (MBL)-producingJAC-antimicrobial resistance · 2025Article
- Biomarker-Driven Pharmacokinetics and Efficacy of Polymyxin B in Critically Ill Patients with XDR-GN Pneumonia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Maximally precise combinations to overcome metallo-β-lactamase-producingAntimicrobial agents and chemotherapy · 2024Article
- 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
- Polymyxin B Pharmacodynamics in the Hollow-Fiber Infection Model: What You See May Not Be What You Get.Antimicrobial agents and chemotherapy · 2021Article
- Acquisition of theInfection and drug resistance · 2021Article
- In pursuit of the triple crown: mechanism-based pharmacodynamic modelling for the optimization of three-drug combinations against KPC-producing Klebsiella pneumoniae.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2020Article
- Using machine learning to optimize antibiotic combinations: dosing strategies for meropenem and polymyxin B against carbapenem-resistant Acinetobacter baumannii.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2020Article
- Polymyxin Combinations CombatmBio · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Objectives: Gram-negative bacteria harbouring the mcr-1 plasmid are resistant to the 'last-line' polymyxins and have been reported worldwide. Our objective was to define the impact of increasing the initial polymyxin B dose intensity against an mcr-1 -harbouring strain to delineate the impact of plasmid-mediated polymyxin resistance on the dynamics of bacterial killing and resistance. Methods: A hollow fibre infection model (HFIM) was used to simulate polymyxin B regimens against an mcr-1 -harbouring Escherichia coli (MIC 8 mg/L) over 10 days. Four escalating polymyxin B 'front-loading' regimens (3.33, 6.66, 13.3 or 26.6 mg/kg for one dose followed by 1.43 mg/kg every 12 h starting 12 h later) simulating human pharmacokinetics were utilized in the HFIM. A mechanism-based, mathematical model was developed using S-ADAPT to characterize bacterial killing. Results: The 3.33 mg/kg 'front-loading' regimen resulted in regrowth mirroring the growth control. The 6.66, 13.3 and 26.6 mg/kg 'front-loading' regimens resulted in maximal bacterial reductions of 1.91, 3.79 and 6.14 log 10 cfu/mL, respectively. Irrespective of the early polymyxin B exposure (24 h AUC), population analysis profiles showed similar growth of polymyxin B-resistant subpopulations. The HFIM data were well described by the mechanism-based model integrating three subpopulations (susceptible, intermediate and resistant). Compared with the susceptible subpopulation of mcr-1 -harbouring E. coli , the resistant subpopulation had an approximately 10-fold lower rate of killing due to polymyxin B treatment. Conclusions: Manipulating initial dose intensity of polymyxin B was not able to overcome plasmid-mediated resistance due to mcr-1 in E. coli . This reinforces the need to develop new combinatorial strategies to combat these highly resistant Gram-negative bacteria.
Indexed as
Identifiers
What OpenQuestion holds
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.