UC Berkeley

Antimicrobial resistance and the subsequent loss of effective antimicrobial treatments is one of the greatest threats facing public health in the 21st century. The increasing prevalence of antimicrobial resistant (AMR) bacteria threatens the effective treatment of common and previously easily treated bacterial infections, such as urinary tract infections (UTIs), and if unaddressed could effectively turn back the clock to a pre-antibiotic era. The complex dynamics of horizontal gene transfer, selective pressure from antimicrobial agent usage and the dissemination of resistant bacterial strains, present a multifaceted problem that will challenge researchers and policy makers, requiring interdisciplinary problem-solving and political will. To slow the spread of resistant strains and limit the impact of antimicrobial resistance selection, global and local public health agencies will require detailed surveillance and improved diagnostic efforts to guide clinical practice. This work attempted to address some of these concerns by examining potential risk factors for AMR UTI through genotypic and geospatial analysis. Our goal was to improve understanding of AMR UTI by leveraging whole genome, patient level and geospatial data. We examined co-resistance of bacteria causing UTI and identified genotypic candidates for resistance markers that may aid in both diagnostic development, as well as surveillance. We also investigated geospatial clustering of UTI by examining common Escherichia coli strains associated with AMR UTI within the community and examined patient characteristics associated with common strains. These approaches to characterize the epidemiology of AMR UTIs have challenged the traditional view that the community prevalence of these infections is largely due to antibiotic selective pressure on E. coli pathogens. Our observations demonstrate that a large proportion of community-onset AMR UTIs are caused by strains of E. coli that are already resistant at the time of infection. This body of work provides the foundation for future investigations of AMR UTI risk factors that will help provide a basis for public health surveillance and intervention.