Monitoring of phenotypic and genotypic changes in antimicrobial resistance in clinical swine bacterial isolates circulating in the U.S.

Abstract

Starting 2017, a Veterinary Feed Directive was implemented in food animal production in the U.S. This directive prohibits the extra-label use and use of medically important antimicrobials for growth promotion. Analysis of long-term trends of antimicrobial resistance (AMR) can help in evaluating the success of such policies. The objectives of this dissertation were to monitor phenotypic and genotypic changes in antimicrobial resistance in clinical swine bacterial isolates (Escherichia coli, Streptococcus suis, Actinobacillus suis, Pasteurella multocida and Haemophilus parasuis) circulating in the U.S. between 2006 to 2016. For E. coli, the prevalence of resistance to most of the antimicrobials remained constant or changed only modestly, with the exception of enrofloxacin resistance which increased from nearly 0% in 2006 to 21% in 2016. For S. suis and P. multocida, prevalence of resistance did not change drastically except for a few antimicrobials. For A. suis and H. parasuis, statistically significant changes were estimated for several antimicrobials. However, a lack of clinical breakpoints or epidemiological cut-offs hindered in the making any clinical or epidemiological inferences. E. coli isolates resistant to ceftiofur and enrofloxacin were selected and whole genome sequencing was conducted on these isolates. Nearly 25% of the ceftiofur resistant E. coli isolates carried ESBL genes and 24% of enrofloxacin resistant isolates carried qnr genes. These genes have been reported only rarely in food animals in USA. Select plasmids carrying ESBL genes were assembled and these were similar to ESBL plasmids present globally. Additionally, these isolates were also found to be carrying mcr-9 and fosA7 genes, which have not been reported in food animals in USA previously. In addition to these studies, a systematic review on global prevalence of AMR in E. coli of swine origin is also presented. This review highlights the disparity between AMR prevalence in high income versus lower-middle income countries and a clear lack of harmonization in studies conducted worldwide.