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Modeling the Effect of Tylosin Phosphate on Macrolide-Resistant Enterococci in Feedlots and Reducing Resistance Transmission.

ABSTRACT: Tylosin phosphate (TYL) is administered to more than 50% of U.S. beef cattle to reduce the incidence of liver abscesses but may increase the risk of macrolide-lincosamide-streptogramin-resistant bacteria disseminating from the feedlot. Limited evidence has been collected to understand how TYL affects the proportion of resistant bacteria in cattle or the feedlot environment. We created a mathematical model to investigate the effects of TYL administration on Enterococcus dynamics and examined preharvest strategies to mitigate the impact of TYL administration on resistance. The model simulated the physiological pharmacokinetics of orally administered TYL and estimated the pharmacodynamic effects of TYL on populations of resistant and susceptible Enterococcus within the cattle large intestine, feedlot pen, water trough, and feed bunk. The model parameters' population distributions were based on the available literature; 1000 Monte Carlo simulations were performed to estimate the likely distribution of outcomes. At the end of the simulated treatment period, the median estimated proportion of macrolide-resistant enterococci was only 1 percentage point higher within treated cattle compared with cattle not fed TYL, in part because the TYL concentrations in the large intestine were substantially lower than the enterococci minimum inhibitory concentrations. However, 25% of the simulated cattle had a >10 percentage point increase in the proportion of resistant enterococci associated with TYL administration, termed the TYL effect. The model predicts withdrawing TYL treatment and moving cattle to an antimicrobial-free terminal pen with a low prevalence of resistant environmental enterococci for as few as 6 days could reduce the TYL effect by up to 14 percentage points. Additional investigation of the importance of this subset of cattle to the overall risk of resistance transmission from feedlots will aid in the interpretation and implementation of resistance mitigation strategies.

SUBMITTER: Stapleton GS

PROVIDER: S-EPMC8020526 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Tylosin phosphate is a macrolide commonly administered to cattle in North America for the control of liver abscesses. This study investigated the effect of in-feed administration of tylosin phosphate to cattle at subtherapeutic levels and its subsequent withdrawal on macrolide resistance using enterococci as an indicator bacterium. Fecal samples were collected from steers that received no antibiotics and steers administered tylosin phosphate (11 ppm) in-feed for 197 days and withdrawn 28 days before slaughter. Enterococcus species isolated from fecal samples were identified through sequencing the groES-EL intergenic spacer region and subject to antimicrobial susceptibility testing, identification of resistance determinants and pulsed-field gel electrophoresis profiling. Tylosin increased (P < 0.05) the proportion of ery(R) and tyl(R) enterococci within the population. Just prior to its removal, the proportion of ery(R) and tyl(R) resistant enterococci began decreasing and continued to decrease after tylosin was withdrawn from the diet until there was no difference (P > 0.05) between treatments on d 225. This suggests that antibiotic withdrawal prior to slaughter contributes to a reduction in the proportion of macrolide resistant enterococci entering the food chain. Among the 504 enterococci isolates characterized, Enterococcus hirae was found to predominate (n = 431), followed by Enterococcus villorum (n = 32), Enterococcus faecium (n = 21), Enterococcus durans (n = 7), Enterococcus casseliflavus (n = 4), Enterococcus mundtii (n = 4), Enterococcus gallinarum (n = 3), Enterococcus faecalis (n = 1), and Enterococcus thailandicus (n = 1). The diversity of enterococci was greater in steers at arrival than at exit from the feedlot. Erythromycin resistant isolates harbored the erm(B) and/or msrC gene. Similar PFGE profiles of ery(R) E. hirae pre- and post-antibiotic treatment suggest that increased abundance of ery(R) enterococci after administration of tylosin phosphate reflects selection for strains that were already present within the gastrointestinal tract of cattle at arrival.

Project description:The misuse/abuse of antibiotics in intensive animal rearing and communities led to the emergence of resistant isolates such as vancomycin-resistant enterococci (VREs) worldwide. This has become a major source of concern for the public health sector. The aim of this study was to report the antibiotic resistance profiles and to highlight the presence of virulence genes in VREs isolated from feedlots cattle of the North-West Province of South Africa. 384 faecal samples, 24 drinking troughs water, and 24 soil samples were collected aseptically from 6 registered feedlots. Biochemical and molecular methods were used to identify and categorise the enterococci isolates. Their antibiotic resistance profiles were assessed and genotypic methods were used to determine their antibiotic resistance and their virulence profiles. 527 presumptive isolates were recovered, out of which 289 isolates were confirmed as Enterococcus sp. Specifically, E. faecalis (9%), E. faecium (10%), E. durans (69%), E. gallinarum (6%), E. casseliflavus (2%), E. mundtii (2%), and E. avium (2%) were screened after molecular assays. VanA (62%), vanB (17%), and vanC (21%) resistance genes were detected in 176 Enterococcus sp., respectively. Moreover, tetK (26), tetL (57), msrA/B (111), and mefA (9) efflux pump genes were detected in 138 VRE isolates. Multiple antibiotic resistances were confirmed in all the VRE isolates of this study; the most common antibiotic resistance phenotype was TETR-AMPR-AMXR-VANR-PENR-LINR-ERYR. CylA, hyl, esp, gelE, and asa1 virulence genes were detected in 86 VREs with the exception of vancomycin-resistant E. mundtii isolates that did not display any virulence factor. Most VRE isolates had more than one virulence genes but the most encountered virulence profile was gelE-hyl. Potentially pathogenic multidrug resistant VREs were detected in this study; this highlights the impact of extensive usage of antimicrobials in intensive animal rearing and its implications on public health cannot be undermined.

Project description:Recent concerns over linkages between antimicrobial resistance in human pathogens and antimicrobial use in livestock have prompted researchers to investigate management strategies that reduce the current reliance on in-feed tylosin to control liver abscesses in feedlot cattle. A total of 7,576 crossbred yearlings were allocated to the study (~253 animals/pen, 10 replicate pens per treatment) and individually randomized to one of three treatments. Tylosin phosphate (11 ppm) was included in-feed (1) for the first 125 days on feed (DOF) (FIRST-78%), (2) for DOF 41 to 161 (LAST-75%), or (3) for the entire feeding period (CON; day 0-161). Fecal composites were collected from the pen floor on days 0, 81, and 160 of the finishing period. Serial dilutions were spread plated for enumeration of enterococci on Bile Esculin Azide (BEA) agar and BEA amended with 8 ?g/ml erythromycin. Results indicated that although the proportion of EryR enterococci increased with DOF (P < 0.01), neither treatment (P = 0.34) or treatment × DOF (P = 0.37) affected antimicrobial resistance. Of the 538 isolates, 97% were enterococci, with mixed species isolated early in the feeding period and only Enterococcus hirae isolated at the end. Isolates were most frequently resistant to tylosin (86%), erythromycin (84%), and doxycycline (31%). Macrolide and tetracycline resistant isolates harbored erm(B), msrC, and tet(L), tet(M), tet(O) genes, respectively. Overall, the proportion of EryR enterococci increased (P < 0.05) in all three treatments over the feeding period. Compared to the control cattle, FIRST-78% cattle had more severe (P < 0.05) liver abscesses, while there was a trend (P < 0.08) for this response in LAST-75% cattle. There was no difference (P > 0.05) in total liver abscesses, growth performance, carcass traits, morbidity, or mortality among treatments. These results support the potential to reduce the duration and therefore quantity of tylosin administered to feedlot cattle during the feeding period without impacting animal productivity.

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Modeling the Effect of Tylosin Phosphate on Macrolide-Resistant Enterococci in Feedlots and Reducing Resistance Transmission.

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