期刊
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
卷 78, 期 17, 页码 6137-6142出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AEM.01078-12
关键词
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资金
- European Research Council (ERC)
- Leverhulme Trust
- Clarendon Funds of the University of Oxford
- National Science Engineering and Research Council of Canada (NSERC)
- Fond Quebecois pour la Recherche sur la Nature et les Technologies (FQRNT)
The evolution of drug resistance among pathogenic bacteria has led public health workers to rely increasingly on multidrug therapy to treat infections. Here, we compare the efficacy of combination therapy (i.e., using two antibiotics simultaneously) and sequential therapy (i.e., switching two antibiotics) in minimizing the evolution of multidrug resistance. Using in vitro experiments, we show that the sequential use of two antibiotics against Pseudomonas aeruginosa can slow down the evolution of multiple-drug resistance when the two antibiotics are used in a specific order. A simple population dynamics model reveals that using an antibiotic associated with high costs of resistance first minimizes the chance of multidrug resistance evolution during sequential therapy under limited mutation supply rate. As well as presenting a novel approach to multidrug therapy, this work shows that costs of resistance not only influences the persistence of antibiotic-resistant bacteria but also plays an important role in the emergence of resistance.
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