title: Association of veterinary third-generation cephalosporin use with the risk of emergence of extended-spectrum-cephalosporin resistance in Escherichia coli from dairy cattle in Japan.
abstract: The use of extended-spectrum cephalosporins in food animals has been suggested to increase the risk of spread of Enterobacteriaceae carrying extended-spectrum β-lactamases to humans. However, evidence that selection of extended-spectrum cephalosporin-resistant bacteria owing to the actual veterinary use of these drugs according to criteria established in cattle has not been demonstrated. In this study, we investigated the natural occurrence of cephalosporin-resistant Escherichia coli in dairy cattle following clinical application of ceftiofur. E. coli isolates were obtained from rectal samples of treated and untreated cattle (n = 20/group) cultured on deoxycholate-hydrogen sulfide-lactose agar in the presence or absence of ceftiofur. Eleven cefazoline-resistant isolates were obtained from two of the ceftiofur-treated cattle; no cefazoline-resistant isolates were found in untreated cattle. The cefazoline-resistant isolates had mutations in the chromosomal ampC promoter region and remained susceptible to ceftiofur. Eighteen extended-spectrum cephalosporin-resistant isolates from two ceftiofur-treated cows were obtained on ceftiofur-supplemented agar; no extended-spectrum cephalosporin-resistant isolates were obtained from untreated cattle. These extended-spectrum cephalosporin-resistant isolates possessed plasmid-mediated β-lactamase genes, including bla(CTX-M-2) (9 isolates), bla(CTX-M-14) (8 isolates), or bla(CMY-2) (1 isolate); isolates possessing bla(CTX-M-2) and bla(CTX-M-14) were clonally related. These genes were located on self-transmissible plasmids. Our results suggest that appropriate veterinary use of ceftiofur did not trigger growth extended-spectrum cephalosporin-resistant E. coli in the bovine rectal flora; however, ceftiofur selection in vitro suggested that additional ceftiofur exposure enhanced selection for specific extended-spectrum cephalosporin-resistant β-lactamase-expressing E. coli clones.
authors.affiliation: Laboratory of Food Microbiology and Food Safety, Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Toyotaka
authors.initials: T
authors.lastname: Sato
authors.affiliation: Laboratory of Food Microbiology and Food Safety, Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Torahiko
authors.initials: T
authors.lastname: Okubo
authors.affiliation: Laboratory of Food Microbiology and Food Safety, Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Usui
authors.affiliation: Department of Microbiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yokota
authors.affiliation: Nemuro District Agriculture Mutual Aid Association, Nakashibetsu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Izumiyama
authors.affiliation: Laboratory of Food Microbiology and Food Safety, Department of Health and Environmental Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tamura
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000382:microbiology*; D015296:Ceftizoxime / Q000031:analogs & derivatives* / Q000494:pharmacology; D018550:Cephalosporin Resistance / Q000235:genetics; D002511:Cephalosporins / Q000494:pharmacology*; D052978:Disk Diffusion Antimicrobial Tests; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D029968:Escherichia coli Proteins / Q000235:genetics; D007564:Japan; D012306:Risk; D001618:beta-Lactamases / Q000235:genetics; D000097623:Cefpodoxime
chemical_list: D000900:Anti-Bacterial Agents; D015296:Ceftizoxime; D002511:Cephalosporins; D029968:Escherichia coli Proteins; D001618:beta-Lactamases; D000097623:Cefpodoxime; C053503:ceftiofur
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