ArticleAntimicrobial agents and chemotherapy2011
Use of an in vitro pharmacodynamic model to derive a moxifloxacin regimen that optimizes kill of Yersinia pestis and prevents emergence of resistance.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- What Antibiotic Exposures Are Required to Suppress the Emergence of Resistance for Gram-Negative Bacteria? A Systematic Review.Clinical pharmacokinetics · 2019Pooled it
- The emergence of linezolid resistance among Enterococci in intestinal microbiota of treated patients is unrelated to individual pharmacokinetic characteristics.Antimicrobial agents and chemotherapy · 2014Trial
- Comparative In Vitro Killing of Key Bovine Respiratory Bacterial Pathogens by Pradofloxacin and Eight Other Veterinary Antimicrobial Agents.Microorganisms · 2025Article
- Beating the Bio-Terror Threat with Rapid Antimicrobial Susceptibility Testing.Microorganisms · 2021Review
- Antibiotic Therapy of Plague: A Review.Biomolecules · 2021Review
- Dose Fractionation of Moxifloxacin for Treatment of Tuberculosis: Impact of Dosing Interval and Elimination Half-Life on Microbial Kill and Resistance Suppression.Antimicrobial agents and chemotherapy · 2021Article
- A Rapid Antimicrobial Susceptibility Test for DeterminingFrontiers in microbiology · 2019Article
- Reducing Antibacterial Development Risk for GSK1322322 by Exploring Potential Human Dose Regimens in Nonclinical Efficacy Studies Using Immunocompetent Rats.Antimicrobial agents and chemotherapy · 2017Article
- Relationship between Fosfomycin Exposure and Amplification of Escherichia coli Subpopulations with Reduced Susceptibility in a Hollow-Fiber Infection Model.Antimicrobial agents and chemotherapy · 2016Article
- A Rapid Molecular Test for Determining Yersinia pestis Susceptibility to Ciprofloxacin by the Quantification of Differentially Expressed Marker Genes.Frontiers in microbiology · 2016Article
- Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1.Antimicrobial agents and chemotherapy · 2015Review
- Hollow-fiber pharmacodynamic studies and mathematical modeling to predict the efficacy of amoxicillin for anthrax postexposure prophylaxis in pregnant women and children.Antimicrobial agents and chemotherapy · 2013Article
- Cethromycin-mediated protection against the plague pathogen Yersinia pestis in a rat model of infection and comparison with levofloxacin.Antimicrobial agents and chemotherapy · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Yersinia pestis, the causative agent of bubonic, septicemic, and pneumonic plague, is classified as a CDC category A bioterrorism pathogen. Streptomycin and doxycycline are the "gold standards" for the treatment of plague. However, streptomycin is not available in many countries, and Y. pestis isolates resistant to streptomycin and doxycycline occur naturally and have been generated in laboratories. Moxifloxacin is a fluoroquinolone antibiotic that demonstrates potent activity against Y. pestis in in vitro and animal infection models. However, the dose and frequency of administration of moxifloxacin that would be predicted to optimize treatment efficacy in humans while preventing the emergence of resistance are unknown. Therefore, dose range and dose fractionation studies for moxifloxacin were conducted for Y. pestis in an in vitro pharmacodynamic model in which the half-lives of moxifloxacin in human serum were simulated so as to identify the lowest drug exposure and the schedule of administration that are linked with killing of Y. pestis and with the suppression of resistance. In the dose range studies, simulated moxifloxacin regimens of ≥175 mg/day killed drug-susceptible bacteria without resistance amplification. Dose fractionation studies demonstrated that the AUC (area under the concentration-time curve)/MIC ratio predicted kill of drug-susceptible Y. pestis, while the C(max) (maximum concentration of the drug in serum)/MIC ratio was linked to resistance prevention. Monte Carlo simulations predicted that moxifloxacin at 400 mg/day would successfully treat human infection due to Y. pestis in 99.8% of subjects and would prevent resistance amplification. We conclude that in an in vitro pharmacodynamic model, the clinically prescribed moxifloxacin regimen of 400 mg/day is predicted to be highly effective for the treatment of Y. pestis infections in humans. Studies of moxifloxacin in animal models of plague are warranted.
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.