Impact of ceftiufor administration in steers on the prevalence and antimicrobial resistance of Campylobacter spp.

Authors: FAN, SICUN - North Carolina State University; FOSTER, DEREK - North Carolina State University; Miller, William - Bill; OSBORNE, JASON - North Carolina State University; KATHARIOU, SOPHIA - North Carolina State University

Submitted to: Microorganisms
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/1/2021
Publication Date: 2/4/2021
Citation: Fan, S., Foster, D., Miller, W.G., Osborne, J., Kathariou, S. 2021. Impact of ceftiufor administration in steers on the prevalence and antimicrobial resistance of Campylobacter spp.. Microorganisms. 9(2):318. https://doi.org/10.3390/microorganisms9020318.
DOI: https://doi.org/10.3390/microorganisms9020318

Interpretive Summary: The human pathogen Campylobacter is commonly isolated from food and food animals. Antibiotics are routinely used in livestock production, with many of these same antibiotics or antibiotics that are similar in structure used to treat infections in humans. The antibiotic ceftiofur is a common therapeutic agent in cattle. However, its effect on cattle Campylobacter populations was unknown. Here, two forms of ceftiofur were administered to steers, with ceftiofur concentrations monitored within the GI tract and fecal samples analyzed for Campylobacter for up to 42 days. Ceftiofur concentrations increased initially but then decreased steadily over time. This study indicated that the use of ceftiofur did not significantly affect the population numbers of Campylobacter within the steer GI tract, although the diversity of Campylobacter species increased following application of the free acid form of ceftiofur. Resistance to ceftiofur did not increase within the Campylobacter population, although resistance to other antibiotics did show an increase following treatment.

Technical Abstract: Bacterial resistance to ceftiofur raises public health concerns due to its extensive veterinary usage and structure similarity with ceftriaxone, employed in human medicine. Two types of ceftiofur, ceftiofur crystalline free acid (CCFA) and ceftiofur hydrochloride (CHCL) are commonly used therapeutically in cattle, but their potential impacts on Campylobacter prevalence and antimicrobial resistance remain poorly understood. In this study, CHCL (2.2 mg/kg, three doses at 24-h intervals) and CCFA (6.6 mg/kg, single dose) were administered separately to two different groups of steers. Active drug concentrations within the gastrointestinal tract were measured non-lethally in real time via ultrafiltration sampling in vivo and fecal samples were analyzed for Campylobacter before and after treatment for up to 42 days. Upon administration of CHCL and CCFA, the concentration of ceftiofur equivalent in the colon increased within 4 and 8 h, respectively, and then declined within 8 and 48 h, respectively. The estimated prevalence of Campylobacter in the first week post-treatment increased in the CCFA group (78.8 vs. 81.3%) but not in the CHCL group (57.5 vs. 45.2%). Furthermore, during this first week the estimated prevalence of Campylobacter for steers receiving CCFA was significantly higher than those receiving CHCL (81.3 vs 45.2%; p=0.0108). The majority of the Campylobacter isolates were Campylobacter jejuni (99.1% and 91.7 % in the CHCL and CCFA group, respectively), with other Campylobacter spp. (C. fetus and C. hyointestinalis) being mostly encountered in CCFA-treated calves in week 1. No significant treatment impacts were noted on ceftiufor minimum inhibitory concentration (MIC) for C. jejuni. The dominant C. jejuni AMR profile in fecal samples had resistance to both tetracycline and kanamycin and was more common after CCFA treatment than pre-treatment (59.5 vs. 33.3%) as well as after CHCL treatment (30.5 vs. 16.7%). However, a treatment effect on AMR cannot be assessed statistically due to the small sample size. A larger number of different sequence types (STs) of C. jejuni were detected in CCFA-treated calves than those treated with CHCL, with five novel STs found exclusively after CCFA treatment. The findings suggested that neither of the ceftiofur preparations significantly impacted Campylobacter prevalence or ceftiufor MIC subsequent to the first week post-treatment, while more diverse Campylobacter species and AMR profiles were found after CCFA treatment. However, CHCL may be preferable due to the lower likelihood of temporary increase in Campylobacter prevalence upon treatment.