Mathematical Model of Plasmid-Mediated Resistance to Ceftiofur in Commensal Enteric <em>Escherichia coli</em> of Cattle

<div><p>Antimicrobial use in food animals may contribute to antimicrobial resistance in bacteria of animals and humans. Commensal bacteria of animal intestine may serve as a reservoir of resistance-genes. To understand the dynamics of plasmid-mediated resistance to cephalosporin ceftiofur in enteric commensals of cattle, we developed a deterministic mathematical model of the dynamics of ceftiofur-sensitive and resistant commensal enteric <em>Escherichia coli</em> (<em>E. coli</em>) in the absence of and during parenteral therapy with ceftiofur. The most common treatment scenarios including those using a sustained-release drug formulation were simulated; the model outputs were in agreement with the available experimental data. The model indicated that a low but stable fraction of resistant enteric <em>E. coli</em> could persist in the absence of immediate ceftiofur pressure, being sustained by horizontal and vertical transfers of plasmids carrying resistance-genes, and ingestion of resistant <em>E. coli</em>. During parenteral therapy with ceftiofur, resistant enteric <em>E. coli</em> expanded in absolute number and relative frequency. This expansion was most influenced by parameters of antimicrobial action of ceftiofur against <em>E. coli</em>. After treatment (>5 weeks from start of therapy) the fraction of ceftiofur-resistant cells among enteric <em>E. coli</em>, similar to that in the absence of treatment, was most influenced by the parameters of ecology of enteric <em>E. coli</em>, such as the frequency of transfer of plasmids carrying resistance-genes, the rate of replacement of enteric <em>E. coli</em> by ingested <em>E. coli</em>, and the frequency of ceftiofur resistance in the latter.</p>