Genomics reveal Staphylococcus aureus persists during long-term urinary catheterization despite antimicrobial therapy and catheter exchanges

Urinary catheters, the most frequently placed medical devices in the US, increase the risk of developing symptomatic catheter-associated urinary tract infection (CAUTI) and asymptomatic bacteriuria (ASB) - the presence of bacteria in the urine - with those requiring long-term urinary catheters (LTUCs) at highest risk. While ASB and CAUTI are caused by a broad range of uropathogens, most remain understudied. We use whole-genome sequencing to investigate the understudied uropathogen, Staphylococcus aureus. Analysis of 153 longitudinal S. aureus isolates previously collected from urinary catheter or urine samples from 20 individuals with LTUCs (average of 8 longitudinal isolates/person) demonstrates that most strains are multidrug resistant (MDR), including methicillin-resistant S. aureus (MRSA), and sequence type 5. Importantly, the same S. aureus strain persisted as ASB for an average of 13 weeks, despite antibiotic exposures or urinary catheter exchanges, and in one case transitioned to symptomatic CAUTI. The longitudinal strains are highly genetically related with few genomic changes and stable antimicrobial resistance and virulence gene carriage. This work demonstrates that MDR S. aureus can persist as ASB long-term and that common strategies to reduce or eliminate microbes from LTUCs were ineffective at eradicating the uropathogen in most cases, despite phenotypic susceptibility to the administered antibiotic.