Abstract
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 Escherichia coli (E. coli) 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 E. coli 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 E. coli. During parenteral therapy with ceftiofur, resistant enteric E. coli expanded in absolute number and relative frequency. This expansion was most influenced by parameters of antimicrobial action of ceftiofur against E. coli. After treatment (>5 weeks from start of therapy) the fraction of ceftiofur-resistant cells among enteric E. coli, similar to that in the absence of treatment, was most influenced by the parameters of ecology of enteric E. coli, such as the frequency of transfer of plasmids carrying resistance-genes, the rate of replacement of enteric E. coli by ingested E. coli, and the frequency of ceftiofur resistance in the latter.
Highlights
The emergence and spread of antimicrobial resistance (AMR) is progressively demarcating the epochal success of antimicrobial therapies of bacterial infections
Nmax corresponded to the scenario, and had no influence on the dynamics observed. pAMR was most sensitive to b and u. b.0.01 allowed reproducing the reported pAMR if there was no ceftiofur resistance among ingested E. coli, u = 0
The values reported by field studies of the fraction of ceftiofurresistant cells among fecal E. coli in the absence of immediate ceftiofur pressure were reproduced in the deterministic analysis with a transfer rate for blaCMY-2-carrying plasmids of 423
Summary
The emergence and spread of antimicrobial resistance (AMR) is progressively demarcating the epochal success of antimicrobial therapies of bacterial infections. Humans may be exposed to AMRbacteria from food animals via occupational exposure or contaminated food products. Human food-borne infections with AMR-bacteria are clinically challenging [1,3]. Ingested strains can become a part of the human enteric microflora [4], and transmit AMR-genetic determinants to other human bacteria [5]. The principal mechanism via which resistance disseminates is horizontal transfer of AMR-genes encoded on conjugative plasmids [6,7,8]. Cattle meat products can be contaminated by animals’ feces, and so the enteric microflora [10]. Minimizing the frequency of AMR in cattle enteric bacteria en masse can aid in decreasing human exposure to AMR-strains
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