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

Ahmad, A., Zachariasen, C., Christiansen, L. E., Græsbøll, K., Toft, N., Matthews, L. , Olsen, J. E. and Nielsen, S. S. (2016) Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment. BMC Microbiology, 16, 118. (doi:10.1186/s12866-016-0724-5) (PMID:27338861) (PMCID:PMC4917987)

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Abstract

Background Combination 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. Results Simulation 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. Conclusion Sequential 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.

Item Type:Articles
Additional Information:Strategiske Forskningsråd (DK) (10-093490).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Matthews, Professor Louise
Authors: Ahmad, A., Zachariasen, C., Christiansen, L. E., Græsbøll, K., Toft, N., Matthews, L., Olsen, J. E., and Nielsen, S. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:BMC Microbiology
Publisher:BioMed Central Ltd.
ISSN:1471-2180
ISSN (Online):1471-2180
Published Online:23 June 2016
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in BMC Microbiology 16:118
Publisher Policy:Reproduced under a Creative Commons License

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