Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment

BMC Microbiology

Research Article

Louise Matthews¹  Kaare Græsbøll²  Lasse Engbo Christiansen²  Søren Saxmose Nielsen³  Amais Ahmad³  John Elmerdahl Olsen⁴  Camilla Zachariasen⁴  Nils Toft⁵ 

[1] Boyd Orr Centre for Population and Ecosystem Health, Institute for Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK;Department of Applied Mathematics and Computer Science, Technical University of Denmark, Richard Petersens Plads, 2800, Lyngby, Denmark;Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Grønnegårdsvej 8, DK-1870, Frederiksberg C, Denmark;Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark;National Veterinary Institute, Section of Epidemiology, Technical University of Denmark, Bulowsvej 27, DK-1870, Frederiksberg C, Denmark;

关键词: Antimicrobial resistance;    Ampicillin;    Tetracycline;    Pharmacodynamic;    Dosing strategies;    Pig;    Bacterial growth;   

DOI  :  10.1186/s12866-016-0724-5

 received in 2015-12-26, accepted in 2016-06-02,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCombination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have considered combination treatments. The current study modeled bacterial growth in the intestine of pigs after intramuscular combination treatment (i.e. using two antibiotics simultaneously) and sequential treatments (i.e. alternating between two antibiotics) in order to identify the factors that favor the sensitive fraction of the commensal flora.Growth parameters for competing bacterial strains were estimated from the combined in vitro pharmacodynamic effect of two antimicrobials using the relationship between concentration and net bacterial growth rate. Predictions of in vivo bacterial growth were generated by a mathematical model of the competitive growth of multiple strains of Escherichia coli.ResultsSimulation studies showed that sequential use of tetracycline and ampicillin reduced the level of double resistance, when compared to the combination treatment. The effect of the cycling frequency (how frequently antibiotics are alternated in a sequential treatment) of the two drugs was dependent upon the order in which the two drugs were used.ConclusionSequential treatment was more effective in preventing the growth of resistant strains when compared to the combination treatment. The cycling frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes.

【 授权许可】

CC BY   
© The Author(s). 2016

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