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
Highlights
IntroductionExtended-spectrum cephalosporins (ESCs; third- and fourthgeneration cephalosporins such as cefpodoxime [CPD], ceftazidime [CAZ], and cefepime [FEP]) are broad-spectrum antimicrobials that have been listed by the World Health Organization (WHO) as critically important for human health [1]
Introduction bLactam antimicrobials are used worldwide in clinical settings
From the 193 strains isolated from CTF-treated cattle, 11 isolates resistant to CFZ were obtained; no CFZ-resistant E. coli was obtained from untreated cattle (p,0.05)
Summary
Extended-spectrum cephalosporins (ESCs; third- and fourthgeneration cephalosporins such as cefpodoxime [CPD], ceftazidime [CAZ], and cefepime [FEP]) are broad-spectrum antimicrobials that have been listed by the World Health Organization (WHO) as critically important for human health [1]. The clinical occurrence of ESC-resistant Enterobacteriaceae has increased [3,4]. Numerous bacterial infections in food-producing animals and humans are treated with first- or second-generation cephalosporins such as cefazoline (CFZ), cefalexin (LEX), and cefuroxime (CXM), and ESCs such as ceftiofur (CTF) and CPD. ESCs used in humans and animals are of the same general class and share the same mode of action, even if they differ chemically [6]. The appearance of ESC-resistant bacteria can be attributable to mechanisms common between humans and animals
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