Ceftiofur, a third-generation cephalosporin antimicrobial, was used in Canadian hatcheries for many years to prevent early mortality in chicks, leading to a high prevalence of cephalosporin resistance in Escherichia coli in chickens. Preventive use of ceftiofur in hatcheries ceased in 2014. We examined the effect of ceftiofur cessation (n ϭ 40 flocks with ceftiofur and n ϭ 28 flocks without antimicrobial at hatchery) and its replacement with an antimicrobial combination, lincomycinspectinomycin (n ϭ 32), at the hatchery on the proportion of samples with E. coli positive for extended-spectrum-␤-lactamase (ESBL) and AmpC ␤-lactamase-related genes, and on the multidrug resistance profiles of ESBL/AmpC-positive E. coli in broilers and their associated breeders (n ϭ 46 samples), at 1 year postcessation. For indicator E. coli from nonenriched media, a significant decrease postcessation in the proportion of samples harboring E. coli isolates positive for bla CMY-2 and/or bla CTX-M was observed. In contrast, following enrichment in medium containing ceftriaxone (1 mg/liter) to facilitate recovery of ESBL/AmpC ␤-lactamase-producing E. coli colonies, both pre-and postcessation, 99% of the samples harbored E. coli positive for bla CMY-2 or bla CTX-M . Among the 15 tested antimicrobial agents, flocks receiving lincomycin-spectinomycin after cessation of ceftiofur showed a significantly greater nonsusceptibility to aminoglycosides, folate inhibitors, phenicols, and tetracyclines and a greater proportion of possible extensively drug-resistant E. coli than those receiving ceftiofur or no antimicrobial at hatchery. This study clearly demonstrates an initial decrease in ESBL/AmpC-positive E. coli following the cessation of ceftiofur in the hatchery but an increase in antimicrobial non-␤-lactam resistance of ESBL/ AmpC-positive E. coli following replacement with lincomycin-spectinomycin. IMPORTANCE Antimicrobial resistance is a global problem. The antimicrobial ceftiofur has been used worldwide for disease prevention in poultry production, resulting in a greatly increased resistance to this antimicrobial important in poultry and human medicine. Our study examined the impact of ceftiofur cessation and its replacement with the antimicrobial combination lincomycin-spectinomycin, a common practice in the industry. Our study demonstrated a decrease in ceftiofur resistance after the cessation of ceftiofur use, although the resistance genes remain ubiquitous in all phases of poultry production, showing that poultry remains a reservoir for ceftiofur resistance and requiring continued vigilance. We also observed a decrease in multidrug resistance involving different antimicrobial classes after cessation of ceftiofur but an increase following use of lincomycin-spectinomycin, indicating that this antimicrobial use should be questioned. Reduced resistance to ceftiofur in poultry may translate to better treatment efficacy, decreased morbidity/mortality, and enhanced food safety for humans.Citation Verrette L, Fairbrother JM, Boulianne M. 2019....

24Ceftiofur, a cephalosporin antimicrobial, was used systematically in Canadian hatcheries 25 for many years to prevent early mortality in chicks leading to a high prevalence of 26 cephalosporin resistance in Escherichia coli in chickens. Preventive use of ceftiofur in 27 hatcheries ceased in 2014. We examined the effect of ceftiofur cessation and replacement 28 with lincomycin-spectinomycin at the hatchery on the proportion of E. coli positive for 29 extended-spectrum β-lactamase (ESBL) and AmpC β-lactamase related genes, and on the 30resistance profiles of ESBL/AmpC positive E. coli in broilers and their 31 associated breeders, at one year post-cessation. For indicator E. coli from non-enriched 32 media, a significant decrease post-cessation in the proportion of samples harboring E. coli 33 isolates positive for bla CMY-2 and/or bla CTX-M was observed. In contrast, following 34 enrichment in medium containing ceftriaxone (1mg/L) to facilitate recovery of 35 ESBL/AmpC β-lactamase producing E. coli colonies, both pre-and post-cessation, 99% 36 of the samples harbored E. coli positive for bla CMY-2 or bla CTX-M . Flocks receiving 37lincomycin-spectinomycin after cessation of ceftiofur showed a significantly greater non-38 susceptibility to aminoglycoside, folate inhibitor, phenicol, tetracycline and possible 39 extensively drug resistant E. coli compared to those receiving ceftiofur or no 40 antimicrobial at hatchery. This study clearly demonstrates an initial decrease in 41 ESBL/AmpC positive E. coli following the cessation of ceftiofur in hatchery but an 42 increase in multidrug resistant E. coli following replacement with lincomycin-43 spectinomycin. 44 Importance 45Antimicrobial resistance is a global problem. The antimicrobial ceftiofur has been used 46 worldwide for disease prevention in poultry production resulting in a greatly increased 47 resistance to this antimicrobial important in poultry and human medicine. Our study 48 examines the impact of ceftiofur cessation and its replacement with the antimicrobial 49 combination lincomycin-spectinomycin, a common practice in the industry. Our study 50 demonstrated a decrease in ceftiofur resistance after the cessation of its use, although the 51 resistance genes remain ubiquitous in all phases of poultry production, showing that 52 poultry remains a reservoir for ceftiofur resistance and requiring continued vigilance. We 53 also observed a decrease in multidrug resistance after cessation of ceftiofur although the 54 contrary finding following use of lincomycin-spectinomycin indicates that the use of 55 these antimicrobials should be questioned. Reduced resistance to ceftiofur in poultry may 56 translate to better treatment efficacy, decreased morbidity, mortality, duration and cost of 57 hospitalization in humans. 58 Introduction 59One of the most important causes of early mortality in broiler chick is omphalitis, mostly 60 caused by avian pathogenic E. coli (APEC), a subgroup of extra-intestinal pathogenic E. 61 coli (ExPEC) (1, 2). Ceftiofur, a third generati...