title: Pharmacokinetic-pharmacodynamic model to evaluate intramuscular tetracycline treatment protocols to prevent antimicrobial resistance in pigs.
abstract: High instances of antimicrobial resistance are linked to both routine and excessive antimicrobial use, but excessive or inappropriate use represents an unnecessary risk. The competitive growth advantages of resistant bacteria may be amplified by the strain dynamics; in particular, the extent to which resistant strains outcompete susceptible strains under antimicrobial pressure may depend not only on the antimicrobial treatment strategies but also on the epidemiological parameters, such as the composition of the bacterial strains in a pig. This study evaluated how variation in the dosing protocol for intramuscular administration of tetracycline and the composition of bacterial strains in a pig affect the level of resistance in the intestine of a pig. Predictions were generated by a mathematical model of competitive growth of Escherichia coli strains in pigs under specified plasma concentration profiles of tetracycline. All dosing regimens result in a clear growth advantage for resistant strains. Short treatment duration was found to be preferable, since it allowed less time for resistant strains to outcompete the susceptible ones. Dosing frequency appeared to be ineffective at reducing the resistance levels. The number of competing strains had no apparent effect on the resistance level during treatment, but possession of fewer strains reduced the time to reach equilibrium after the end of treatment. To sum up, epidemiological parameters may have more profound influence on growth dynamics than dosing regimens and should be considered when designing improved treatment protocols.
authors.affiliation: Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Amais
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Department of Applied Mathematics and Computer Science, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Græsbøll
authors.affiliation: Department of Applied Mathematics and Computer Science, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Lasse Engbo
authors.initials: LE
authors.lastname: Christiansen
authors.affiliation: National Veterinary Institute, Section of Epidemiology, Technical University of Denmark, Frederiksberg C, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Toft
authors.affiliation: 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, United Kingdom.
authors.forename: Louise
authors.initials: L
authors.lastname: Matthews
authors.affiliation: Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark saxmose@sund.ku.dk.
authors.forename: Søren Saxmose
authors.identifier: http://orcid.org/0000-0003-2417-0787
authors.initials: SS
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002985:Clinical Protocols; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy; D007273:Injections, Intramuscular / Q000379:methods; D008826:Microbial Sensitivity Tests / Q000379:methods; D013552:Swine; D013752:Tetracycline / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D013752:Tetracycline