Role of Ceftiofur in Selection and Dissemination of bla CMY-2 -Mediated Cephalosporin Resistance in Salmonella enterica and Commensal Escherichia coli Isolates from Cattle

Third-generation cephalosporin resistance ofSalmonella and commensalEscherichia coli isolates from cattle in the United States is predominantly conferred by the cephamycinase CMY-2, which inactivates β-lactam antimicrobial drugs used to treat a wide variety of infections, including pediatric salmonellosis. The emergence and dissemination ofbla CMY-2 - -bearing plasmids followed and may in part be the result of selection pressure imposed by the widespread utilization of ceftiofur, a third-generation veterinary cephalosporin. This study assessed the potential effects of ceftiofur onbla CMY-2 transfer and dissemination by (i) an in vivo experimental study in which calves were inoculated with competentbla CMY-2 -bearing plasmid donors and susceptible recipients and then subjected to ceftiofur selection and (ii) an observational study to determine whether ceftiofur use in dairy herds is associated with the occurrence and frequency of cephalosporin resistance inSalmonella and commensalE. coli . The first study revealedbla CMY-2 plasmid transfer in both ceftiofur-treated and untreated calves but detected no enhancement of plasmid transfer associated with ceftiofur treatment. The second study detected no association (P = 0.22) between ceftiofur use and either the occurrence of ceftiofur-resistant salmonellosis or the frequency of cephalosporin resistance in commensalE. coli . However, herds with a history of salmonellosis (including both ceftiofur-resistant and ceftiofur-susceptibleSalmonella isolates) used more ceftiofur than herds with no history of salmonellosis (P = 0.03) These findings fail to support a major role for ceftiofur use in the maintenance and dissemination ofbla CMY-2 -bearing plasmid mediated cephalosporin resistance in commensalE. coli and in pathogenicSalmonella in these dairy cattle populations.