ArticlePLoS computational biology2016
Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?
Article in PLoS computational biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis 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.
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.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Prophylactic Cefazolin Dosing in Obesity-a Systematic Review.Obesity surgery · 2022Pooled it
- Evolutionary Double-Bind Treatment Using Radiation Therapy and Natural Killer Cell-Based Immunotherapy in Prostate Cancer.International journal of radiation oncology, biology, physics · 2026Article
- Optimizing insecticide deployment strategies to delay quantitative resistance in mosquito populations.Journal of mathematical biology · 2026Article
- Article
- The speed of vaccination rollout and the risk of pathogen adaptation.Journal of the Royal Society, Interface · 2025Article
- Observational study of antibiotic prescribing patterns by age and sex in primary care in England: why we need to take this variation into account to evaluate antibiotic stewardship and predict AMR variation.JAC-antimicrobial resistance · 2025Article
- Developmental synchrony and extraordinary multiplication rates in pathogenic organisms.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- Impacts of limits to adaptation on population and community persistence in a changing environment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance.The Journal of infectious diseases · 2024Article
- Evaluation of Pharmacy Intern Interventions on Antimicrobial Use in University-Affiliated Hospitals: A Retrospective Analysis.Journal of clinical medicine · 2024Article
- When does antimicrobial resistance increase bacterial fitness? Effects of dosing, social interactions, and frequency dependence on the benefits of AmpCEvolution letters · 2024Article
- Linking within- and between-host scales for understanding the evolutionary dynamics of quantitative antimicrobial resistance.Journal of mathematical biology · 2023Article
- A stochastic analysis of the interplay between antibiotic dose, mode of action, and bacterial competition in the evolution of antibiotic resistance.PLoS computational biology · 2023Article
- Review
- Hygiene may attenuate selection for antibiotic resistance by changing microbial community structure.Evolution, medicine, and public health · 2023Article
- The future of evolutionary medicine: sparking innovation in biomedicine and public health.Frontiers in science · 2023Article
- β-Lactam Dosing in Critical Patients: A Narrative Review of Optimal Efficacy and the Prevention of Resistance and Toxicity.Antibiotics (Basel, Switzerland) · 2022Review
- The risk of drug resistance during long-acting antimicrobial therapy.Proceedings. Biological sciences · 2022Article
- Bacteriomimetic Liposomes Improve Antibiotic Activity of a Novel Energy-Coupling Factor Transporter Inhibitor.Pharmaceutics · 2021Article
- Enrofloxacin Alters Fecal Microbiota and Resistome Irrespective of Its Dose in Calves.Microorganisms · 2021Article
9 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
2 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients.
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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.