Dynamics of extended spectrum beta-lactamase producing, third generation cephalosporin-resistant and tetracycline-resistant Escherichia coli in feedlot cattle with or without tylosin administration

Authors: Agga, Getahun; GALLOWAY, HUNTER - Western Kentucky University

Submitted to: Journal of Food Protection
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/12/2023
Publication Date: 8/18/2023
Citation: Agga, G.E., Galloway, H.O. 2023. Dynamics of extended spectrum beta-lactamase producing, third generation cephalosporin-resistant and tetracycline-resistant Escherichia coli in feedlot cattle with or without tylosin administration. Journal of Food Protection. https://doi.org/10.1016/j.jfp.2023.100144.
DOI: https://doi.org/10.1016/j.jfp.2023.100144

Interpretive Summary: Liver abscess causes severe economic loss to beef cattle industry. It occurred commonly in feedlot cattle on high grain diet. To control liver abscess, antibiotics are administered to feedlot cattle through feed continuously. Tylosin is by far the most commonly used antibiotic for this purpose. Although tylosin is a veterinary only antibiotic, its analogs erythromycin and azithromycin are critically important antibiotics for the treatment of severe infections in humans. Therefore, the use of tylosin in feedlot cattle can select for bacteria resistant to these antibiotics. Previous studies have shown that the use of tylosin in feedlot cattle selects for erythromycin resistant Gram-positive enterococci bacteria. However, the impact of using tylosin on Gram-negative foodborne enteric bacteria resistant to antibiotics important for human health is not well understood. To fill this gap, we conducted an experimental study that evaluated the impact of tylosin use in feedlot cattle on the levels of tetracycline, third generation cephalosporins and extended spectrum beta-lactamase enzyme producing Escherichia coli (E. coli) bacteria from the fecal samples collected over the feeding period from cattle with or without tylosin feed supplementation. Tylosin supplementation did not impact the levels of tetracycline and third generation cephalosporin resistant E. coli. However, cattle which received tylosin supplemented feed were more likely to carry extended spectrum beta-lactamase enzyme producing E. coli. The pen surface (cattle manure) samples also contained E. coli resistant to the antibiotics we studied. The fact that tylosin use in feedlot cattle did not select for tetracycline and third generation cephalosporin resistant Gram-negative bacteria E. coli is a positive finding. On the other hand, the increased detection of extended spectrum beta-lactamase enzyme producing enetric bacteria such as E. coli in tylosin medicated cattle is concerning. The extended spectrum beta-lactamase enzymes inactivate a wide range of beta-lactam antibiotics including the last resort antibiotics such as the third and higher generation cephalosporins necessary to treat life threatening bacterial infections in humans. Due to their significant public health risk, the Centers for Disease Control and Prevention considers extended spectrum beta-lactamase enzyme producing bacteria as a serious threat. Such resistant bacteria can reach people through contaminated beef, if not well cooked. Additional pathways are when the bacteria disseminate into the environment through manure land application for produce production, or through run-off from the feedlot or cattle manure amended cropland contaminating water sources. Although this finding is critical, the result should be interpreted cautiously since our study was limited in scope. Additional studies involving large feedlots are required to replicate our results. We note that tylosin is approved for use in the feed of feedlot cattle for the purpose of preventing liver abscess. The use of tylosin to prevent liver abscess is also animal welfare issue. Therefore, the use of tylosin for beef cattle production should be assessed by considering its animal health and economic benefits against its collateral risk of selecting for antibiotic resistant bacteria of public health importance.

Technical Abstract: The impact of in-feed use of tylosin in feedlot cattle on Gram-negative foodborne bacteria is unknown. We evaluated the effect of continuous in-feed tylosin use on the concentration and prevalence of tetracycline resistant (TETr)-, 3rd generation cephalosporin resistant (3GCr)-, and extended spectrum ß-lactamase producing (ESBLs)-E. coli in feedlot cattle. A cohort of weaned calves (10 animals/group) were randomized to receive feed with or without tylosin. Fecal samples, regularly collected over the entire feeding period, and pen surface and feed samples, collected at the end of the feeding period, were cultured on selective media. Enumeration and binary outcomes were analyzed by mixed effects linear regression or logistic regression, respectively using treatment and days on feed as fixed factors, and animal ID as a random variable. Tylosin supplementation did not affect the fecal concentrations of TETr E. coli or fecal prevalence of 3GCr E. coli. However, cattle in the tylosin group were 1.5 times more likely (Odds ratio=1.5: 95% confidence interval: 1.1 - 2.0) to harbor ESBLs E. coli than the control cattle. Regardless of tylosin treatment, fecal concentrations of TETr E. coli and the prevalence of 3GCr- and ESBLs-E. coli increased over time. Tylosin supplemented feed did not affect the prevalence of TETr E. coli and 3GCr and ESBLs-E. coli were not detected from the feed samples. Tylosin treatment did not affect the concentrations of TETr E. coli and the prevalence of 3GCr- and ESBLs-E. coli in the pen-surface samples. In summary, although in-feed tylosin use in feedlot cattle did not select for TETr- and 3GCr-E. coli, it increased the likelihood of detecting ESBLs-producing E. coli. Furthermore, the study indicated that feedlot production setting gradually increases the levels of E. coli resistant to the critically and/or important antibiotics for public health, indicating an increased risk of their dissemination beyond feedlot environment.