Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Mathematical modeling links benefits of short and long antibiotic treatment to details of infection

Francisco F. S. Paupério, View ORCID ProfileVitaly V. Ganusov, View ORCID ProfileErida Gjini
doi: https://doi.org/10.1101/555334
Francisco F. S. Paupério
aInstituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal
cDepartamento de Informática, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016, Lisbon, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vitaly V. Ganusov
bDepartment of Microbiology, University of Tennessee, Knoxville, TN 37996, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Vitaly V. Ganusov
Erida Gjini
aInstituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Erida Gjini
  • For correspondence: egjini@igc.gulbenkian.pt
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Antibiotics are the major tool for treating bacterial infections. With rising antibiotic resistance in microbes, strategies that limit further evolution and spread of drug resistance are urgently needed, in individuals and populations. While classical recommendations favor longer and aggressive treatments, more recent studies and clinical trials advocate for moderate regimens. In this debate, two axes of aggressive treatment have typically been conflated: treatment intensity and treatment duration, the latter being rarely addressed by mathematical models. Here, by using a simple mathematical model of a generic bacterial infection, controlled by host’s immune response, we investigate the role of treatment timing and antibiotic efficacy in determining optimal duration of treatment. We show that even in such simple mathematical model, it is impossible to select for universally optimal treatment duration. In particular, short (3 day) or long (7 day) treatments may be both beneficial depending on treatment onset, on the criterion used, and on the antibiotic efficacy. This results from the dynamic trade-off between immunity and resistance in acute, self-limiting infections, and uncertainty relating symptoms to the start of infection. We find that treatment timing can shift the trend between resistance selection and length of antibiotic exposure in individual hosts. We propose that major advances in predicting impact of antibiotics on bacterial infections must come from deeper experimental understanding of bacterial infection dynamics in humans. To guide rational therapy, mathematical models need to be constrained by data, including details of pathology and symptom thresholds in patients, and of host immune control of infection.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted August 14, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Mathematical modeling links benefits of short and long antibiotic treatment to details of infection
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Mathematical modeling links benefits of short and long antibiotic treatment to details of infection
Francisco F. S. Paupério, Vitaly V. Ganusov, Erida Gjini
bioRxiv 555334; doi: https://doi.org/10.1101/555334
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Mathematical modeling links benefits of short and long antibiotic treatment to details of infection
Francisco F. S. Paupério, Vitaly V. Ganusov, Erida Gjini
bioRxiv 555334; doi: https://doi.org/10.1101/555334

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Systems Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4115)
  • Biochemistry (8818)
  • Bioengineering (6522)
  • Bioinformatics (23466)
  • Biophysics (11792)
  • Cancer Biology (9212)
  • Cell Biology (13326)
  • Clinical Trials (138)
  • Developmental Biology (7439)
  • Ecology (11413)
  • Epidemiology (2066)
  • Evolutionary Biology (15155)
  • Genetics (10439)
  • Genomics (14045)
  • Immunology (9173)
  • Microbiology (22159)
  • Molecular Biology (8814)
  • Neuroscience (47581)
  • Paleontology (350)
  • Pathology (1429)
  • Pharmacology and Toxicology (2492)
  • Physiology (3731)
  • Plant Biology (8082)
  • Scientific Communication and Education (1437)
  • Synthetic Biology (2221)
  • Systems Biology (6039)
  • Zoology (1253)