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Updated: Jan 16, 2026
11:17
Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
13.4K
A General Analytic Approach to Predicting the Best Antibiotic Dosing Regimen
Leah Childers1, Pia Abel Zur Wiesch2, Jessica M Conway1
1Department of Mathematics, Pennsylvania State University, University Park PA, U.S.A.
Biorxiv : the Preprint Server for Biology
|September 26, 2025
Summary
Optimal antibiotic dosing depends on the dose-response curve
Area of Science:
- Pharmacology
- Mathematical Biology
- Infectious Diseases
Background:
- Optimal antibiotic dosing strategies remain unclear, with varying clinical practices.
- Some antibiotics are best administered in continuous low doses, others require pulsed high doses.
- The ideal approach for specific antibiotic-bacterial infection combinations is not well-defined.
Purpose of the Study:
- To analyze bacterial population dynamics under constant concentration versus repeated dosing strategies.
- To determine the key factors influencing optimal antibiotic dosing regimens.
- To challenge the 'hit hard and hit early' paradigm.
Main Methods:
- Utilized mathematical modeling to simulate bacterial populations.
- Analyzed two dosing strategies: constant concentration and repeated dosing.
- Incorporated fixed pharmacokinetic and pharmacodynamic properties into the models.
Main Results:
- The shape of the antibiotic dose-response curve is critical in determining optimal dosing.
- Curve concavity dictates whether constant or repeated dosing is superior.
- Multiple concavities necessitate consideration of dosing range and tolerability.
Conclusions:
- Antibiotic dosing optimization is complex and depends on dose-response curve characteristics.
- The universal 'hit hard and hit early' approach may not always be optimal.
- Findings support rational antibiotic prescription to minimize use and combat resistance.
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