title: How fitness reduced, antimicrobial resistant bacteria survive and spread: a multiple pig-multiple bacterial strain model.
abstract: More than 30% of E. coli strains sampled from pig farms in Denmark over the last five years were resistant to the commonly used antimicrobial tetracycline. This raises a number of questions: How is this high level sustained if resistant bacteria have reduced growth rates? Given that there are multiple susceptible and resistant bacterial strains in the pig intestines, how can we describe their coexistence? To what extent does the composition of these multiple strains in individual pigs influence the total bacterial population of the pig pen? What happens to a complex population when antimicrobials are used? To investigate these questions, we created a model where multiple strains of bacteria coexist in the intestines of pigs sharing a pen, and explored the parameter limits of a stable system; both with and without an antimicrobial treatment. The approach taken is a deterministic bacterial population model with stochastic elements of bacterial distributions and transmission. The rates that govern the model are process-oriented to represent growth, excretion, and uptake from environment, independent of herd and meta-population structures. Furthermore, an entry barrier and elimination process for the individual strains in each pig were implemented. We demonstrate how competitive growth between multiple bacterial strains in individual pigs, and the transmission between pigs in a pen allow for strains of antimicrobial resistant bacteria to persist in a pig population to different extents, and how quickly they can become dominant if antimicrobial treatment is initiated. The level of spread depends in a non-linear way of the parameters that govern excretion and uptake. Furthermore, the sampling of initial distributions of strains and stochastic transmission events give rise to large variation in how homogenous and how resistant the bacterial population becomes. Most important: resistant bacteria are demonstrated to survive with a disadvantage in growth rate of well over 10%.
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 Large Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Søren Saxmose
authors.initials: SS
authors.lastname: Nielsen
authors.affiliation: Department of Large Animal Sciences, University of Copenhagen, Frederiksberg, Denmark; National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Toft
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
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D034421:Sus scrofa / Q000382:microbiology*; D013752:Tetracycline / Q000494:pharmacology*; D013753:Tetracycline Resistance
chemical_list: D000900:Anti-Bacterial Agents; D013752:Tetracycline