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High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Statistical metamodeling for revealing synergistic antimicrobial interactions
Hsiang Chia Chen1, Chia Hsiang Chen, Vincent Gau
1Department of Aerospace and Mechanical Engineering, University of Arizona, Tucson, Arizona, USA.
Plos One
|December 3, 2010
Summary
A new method rapidly screens antibiotic combinations, identifying a potent trimethoprim-gentamicin cocktail effective against drug-resistant bacteria. This approach accelerates the discovery of synergistic antimicrobial treatments for public health.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Rising antimicrobial resistance poses a significant public health threat.
- The development of new antibiotics lags behind the emergence of resistant bacterial strains.
- Efficient screening methods are needed to identify effective antimicrobial combinations.
Purpose of the Study:
- To demonstrate a metamodel antimicrobial cocktail optimization (MACO) scheme for rapid screening of antibiotic cocktails.
- To identify synergistic antimicrobial combinations against uropathogenic clinical isolates.
- To establish a generic platform for discovering novel antimicrobial therapies.
Main Methods:
- Utilized a metamodel antimicrobial cocktail optimization (MACO) scheme.
- Screened hundreds of possible antibiotic combinations using uropathogenic clinical isolates.
- Performed sensitivity analysis and validation studies.
Main Results:
- Identified a synergistic interaction between trimethoprim and gentamicin.
- The MACO scheme required only 18 parallel trials to find an effective cocktail.
- Gentamicin acted as a synergist, reducing trimethoprim's minimum inhibitory concentration 40-fold.
- The trimethoprim-gentamicin cocktail demonstrated efficacy against multiple uropathogenic strains.
Conclusions:
- The MACO scheme offers an effective and simple method for identifying synergistic antimicrobial cocktails.
- This approach has the potential to accelerate the management of bacterial infections.
- The identified trimethoprim-gentamicin combination shows promise for clinical application.
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