The effect of tylosin on antimicrobial resistance in beef cattle enteric bacteria: A systematic review and meta-analysis

Tylosin is a commonly used in-feed antimicrobial and is approved in several countries to reduce the incidence of liver abscesses in beef cattle. Macrolides are critically important antimicrobials in human health and used to treat some foodborne bacterial diseases, such as Campylobacter jejuni and Salmonella. Feeding tylosin could select for resistant enteric bacteria in cattle, which could contaminate beef products at slaughter and potentially cause foodborne illness. We conducted a systematic review and meta-analysis to evaluate the impact of feeding tylosin to cattle on phenotypic and genotypic resistance in several potential zoonotic enteric bacteria: Enterococcus species, Escherichia coli, Salmonella enterica subspecies enterica, and Campylobacter species. This review was registered with PROSPERO (#CRD42018085949).Eleven databases were searched for primary research studies that fed tylosin at approved doses to feedlot cattle and tested bacteria of interest for phenotypic or genotypic resistance. We screened 1,626 citations and identified 13 studies that met the inclusion criteria. Enterococcus species were tested in seven studies, Escherichia coli was isolated in five studies, three studies reported on Salmonella, and two studies reported on Campylobacter species. Most studies relied on phenotypic antimicrobial susceptibility testing and seven also reported resistance gene testing. A random-effects meta-analyses of erythromycin-resistant enterococci from four studies had significant residual heterogeneity. Only two studies were available for a meta-analysis of tylosin-resistant enterococci. A semi-quantitative analysis demonstrated an increase in macrolide-resistant enterococci after long durations of tylosin administration (>100 days). Semi-quantitative analyses of other bacteria-antimicrobial combinations revealed mixed results, but many comparisons found no effect of tylosin administration. However, about half of these no-effect comparisons did not record the cumulative days of tylosin administration or the time since the last dose.When fed at approved dosages for typical durations, tylosin increases the proportion of macrolide-resistant enterococci in the cattle gastrointestinal tract, which could pose a zoonotic risk to human beef consumers. Feeding tylosin for short durations may mitigate the impact on macrolide-resistant enterococci and further studies are encouraged to determine the effect of minimizing or eliminating tylosin use in beef cattle. There may also be an impact on other bacteria and other antimicrobial resistances but additional details or data are needed to strengthen these comparisons. We encourage authors of antimicrobial-resistance studies to follow reporting guidelines and publish details of all comparisons to strengthen future meta-analyses.