Effect of continuous in-feed administration of tylosin to feedlot cattle on macrolide and tetracycline resistant enterococci in a randomized field trial

Authors: Agga, Getahun; GALLOWAY, HUNTER - Western Kentucky University; APPALA, KEERTHI - Western Kentucky University; MAHMOUDI, FARANAK - Western Kentucky University; KASUMBA, JOHN - Western Kentucky University; Loughrin, John; CONTE, ERIC - Western Kentucky University

Submitted to: Preventive Veterinary Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/3/2023
Publication Date: 5/5/2023
Citation: Agga, G.E., Galloway, H., Appala, K., Mahmoudi, F., Kasumba, J., Loughrin, J.H., Conte, E. 2023. Effect of continuous in-feed administration of tylosin to feedlot cattle on macrolide and tetracycline resistant enterococci in a randomized field trial. Preventive Veterinary Medicine. 215. Article 105930. https://doi.org/10.1016/j.prevetmed.2023.105930.
DOI: https://doi.org/10.1016/j.prevetmed.2023.105930

Interpretive Summary: Liver abscess causes an estimated annual loss of $16 million to U.S. beef industry. Tylosin is an antibiotic continuously added to cattle feed to prevent liver abscesses in the feedlots. However, the continuous use of antibiotics has raised concerns regarding antibiotic resistance. In this research, we examined erythromycin-resistant and tetracycline-resistant enterococci bacteria in two groups of beef cattle: one group received tylosin in the feed and another group received no tylosin during their feeding period. Antibiotic resistance changes in feedlot cattle were monitored from weaning to harvest. Feces, feed and pen surface samples were collected approximately monthly and cultured. Molecular markers were used to identify resistance genes in the resistant enterococci bacteria and to quantify their abundance directly from the samples using culture independent method. The species of the enterococci isolates and the concentration of the antibiotic itself in feces were determined. Continuous use of tylosin to preventing liver abscess in beef cattle increases the abundance of macrolide resistant enterococci while concurrently decreasing the total enterococci and tetracycline resistant population. The two most common species often associated with hospital acquired infections in humans were readily detected in the feedlot cattle, feed and environmental samples. The excretion of tylosin in the feces of medicated cattle can further select for resistant bacteria in natural environments such as soil and water. Our study shows the need for other approaches that can minimize the antimicrobial resistance effect of tylosin while maintaining beef cattle health and production.

Technical Abstract: Liver abscess causes substantial economic loss to the beef cattle industry through liver condemnation, reduced animal performance and carcass yield. Continuous in-feed use of tylosin is the most effective and a commonly used practice in beef cattle production to prevent liver abscesses. However, such mass medication can increase the level of antimicrobial resistant bacteria. We investigated the effect of continuous in-feed use of tylosin in feedlot cattle on: (i) concentrations and prevalence of erythromycin-resistant (ERYr) and tetracycline-resistant (TETr) enterococci; (ii) associated antimicrobial resistance genes (ARGs) for resistance; (iii) species distribution; iv) macrolide and tetracycline resistance gene concentrations; and (v) tylosin concentration. A cohort of weaned calves were randomized to receive tylosin-medicated feed (Tylosin; n=10) or nonmedicated feed (Control; n=10) for full feedlot cycle. Feces, feed and pen-surface samples were collected and processed by culture, droplet digital PCR and liquid chromatography/mass spectroscopy for bacterial enumeration, detection and characterization, ARG quantification and tylosin concentration, respectively. Data were analyzed by multilevel, linear or binary regression models depending on the outcomes. Tylosin administration significantly increased fecal concentration (P<0.001) and prevalence (P=0.021) of ERYr enterococci and ermB gene concentration (P<0.001), compared to the control group. Interestingly, tylosin administration significantly reduced (P=0.037) fecal TETr enterococci concentration compared to the control group, with no significant effect (P=0.758) on fecal tetM concentration. In both treatment groups, enterococci concentrations increased over time, peaking on 174 days in feed before returning to the baseline. ERYr enterococci concentration was significantly (P=0.012) higher in tylosin medicated feeds, with no significant effect (P=0.321) on TETr enterococci concentration. Pen-surface concentration of ermB was significantly (P=0.024) higher in the tylosin group, with no significant effect (P>0.05) on bacterial concentrations. Increased diversity and a shift in the composition of enterococcal species and ARGs were observed over time, although tylosin use did not significantly affect (P>0.05) their prevalence. Tylosin concentration was significantly higher (P<0.001) in the feces of tylosin administered cattle and medicated feed (P=0.027), with numerically higher pen-surface concentration (P=0.065) in the tylosin group. In conclusion, continuous in-feed use of tylosin in feedlot cattle increases macrolide resistant enterococci, while decreasing tetracycline resistance. Two medically important species, E. faecium and E. faecalis, were predominant regardless of resistance status or sample source. Risk-based approaches including label changes to limit tylosin use such as withdrawal period, and development of effective manure treatments are potential areas of research to reduce environmental and public health impacts.