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Updated: May 13, 2026
07:51
High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method
Published on: May 21, 2018
Quantifying subpopulation synergy for antibiotic combinations via mechanism-based modeling and a sequential dosing
Cornelia B Landersdorfer1, Neang S Ly, Hongmei Xu
1Centre for Medicine Use and Safety, Monash University, Parkville Campus, Parkville, Victoria, Australia.
Antimicrobial Agents and Chemotherapy
|March 13, 2013
Summary
Nisin combined with amikacin demonstrated subpopulation synergy against methicillin-resistant Staphylococcus aureus, showcasing an efficient strategy for evaluating antibiotic combinations and their mechanisms.
Area of Science:
- Microbiology
- Pharmacology
- Mathematical Modeling
Background:
- Antibiotic resistance necessitates novel combination therapies.
- Quantitative modeling aids in understanding drug interactions and optimizing treatment strategies.
Purpose of the Study:
- To develop an efficient experimental and modeling strategy for evaluating antibiotic synergy mechanisms.
- To assess the efficacy of nisin combined with amikacin or linezolid against Staphylococcus aureus subpopulations.
Main Methods:
- Time-kill experiments with serial viable counts over 48 hours.
- Sequential and simultaneous dosing designs with quantitative modeling using S-ADAPT and NONMEM.
- Development of a mechanism-based model with six bacterial populations.
Main Results:
- Nisin plus amikacin achieved subpopulation synergy, demonstrating enhanced killing of resistant strains.
- The developed model accurately described individual bacterial population responses to antibiotic combinations.
- Linezolid inhibited bacterial replication but was less effective against nisin-resistant populations.
Conclusions:
- The proposed sequential and simultaneous dosing design is an efficient approach for characterizing antibiotic synergy.
- This strategy enables quantitative assessment of antibiotic combinations and prospective evaluation of dosing strategies.
- Nisin and amikacin combination therapy shows promise for combating resistant bacterial infections.
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