Abstract
The U.S. Food and Drug Administration recently issued new rules for using ceftiofur in food animals in part because of an increasing prevalence of enteric bacteria that are resistant to 3rd-generation cephalosporins. Parenteral ceftiofur treatment, however, has limited effects on enteric bacteria so we tested the hypothesis that excreted ceftiofur metabolites exert significant selection pressure for ceftiofur-resistant Escherichia coli in soil. Test matrices were prepared by mixing soil with bovine feces and adding urine containing ceftiofur metabolites (CFM) (0 ppm, ∼50 ppm and ∼100 ppm). Matrices were incubated at 23°C or 4°C for variable periods of time after which residual CFM was quantified using a bioassay. Bla CMY-2 plasmid-bearing ceftiofur resistant (cefR) E. coli and one-month old calves were used to study the selection effects of CFM and transmission of cefR bacteria from the environment back to animals. Our studies showed that urinary CFM (∼13 ppm final concentration) is biologically degraded in soil within 2.7 days at 23°C, but persists up to 23.3 days at 4°C. Even short-term persistence in soil provides a >1 log10 advantage to resistant E. coli populations, resulting in significantly prolonged persistence of these bacteria in the soil (∼two months). We further show that resistant strains readily colonize calves by contact with contaminated bedding and without antibiotic selection pressure. Ceftiofur metabolites in urine amplify resistant E. coli populations and, if applicable to field conditions, this effect is far more compelling than reported selection in vivo after parenteral administration of ceftiofur. Because ceftiofur degradation is temperature dependent, these compounds may accumulate during colder months and this could further enhance selection as seasonal temperatures increase. If cost-effective engineered solutions can be developed to limit ex vivo selection, this may limit proliferation for ceftiofur resistant enteric bacteria while preserving the ability to use this important antibiotic in food animal production.
Highlights
Antibiotic resistance is a significant public health concern and in response the U.S Food and Drug Administration has issued new rules for cephalosporin use in food animals [1]
Studies conducted by Subbiah et al [12] showed that long-term maintenance of blaCMY-2 plasmids in resistant E. coli hosts require some level of selection pressure, and ceftiofur use in livestock has been implicated in this process [13,14]
To quantify ceftiofur metabolites (CFM) residues, matrices were mixed with water (50:50 w/v) and filter-sterilized supernatant from these slurries was added to ceftiofur susceptible E. coli K-12 culture [20]
Summary
Antibiotic resistance is a significant public health concern and in response the U.S Food and Drug Administration has issued new rules for cephalosporin use in food animals [1]. The prevalence of blaCMY-2 plasmid-bearing Salmonella and Escherichia coli has increased rapidly in the U.S cattle population over the last decade [4,5,6,7,8,9]. The use of ceftiofur in food animals has increased due to its high effectiveness, convenient formulations, short withholding, and increased label indications. This increased use has been accompanied by a parallel increase in the prevalence of ceftiofur resistant (cefR) enteric bacteria in food animal populations [13,14,15,16,17]
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