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Genomics reveal Staphylococcus aureus persists during long-term urinary catheterization despite antimicrobial therapy
Jesus M Duran Ramirez1, Chelsie E Armbruster2, Blake M Hanson3,4
1Department of Microbiology and Molecular Genetics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Abstract:
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.
Insights
Multidrug-resistant Staphylococcus aureus, including MRSA, can persist as asymptomatic bacteriuria (ASB) in long-term urinary catheter users for weeks. Standard treatments often fail to eradicate these persistent S. aureus ASB infections.
Area of Science:
- Microbiology and Infectious Diseases
- Genomics and Bioinformatics
- Medical Devices and Healthcare-Associated Infections
Background:
- Urinary catheters are common medical devices associated with increased risk of catheter-associated urinary tract infections (CAUTI) and asymptomatic bacteriuria (ASB).
- Long-term urinary catheter (LTUC) users are at the highest risk for these infections, which are often caused by understudied uropathogens.
- Staphylococcus aureus is an understudied uropathogen frequently implicated in CAUTI and ASB.
Purpose of the Study:
- To investigate the genomic characteristics and persistence of Staphylococcus aureus in individuals with LTUCs.
- To understand the genetic relatedness and antimicrobial resistance profiles of S. aureus strains causing ASB and CAUTI.
- To evaluate the effectiveness of common interventions against persistent S. aureus ASB in LTUC users.
Main Methods:
- Whole-genome sequencing was employed to analyze 153 longitudinal S. aureus isolates from 20 LTUC patients.
- Isolates were collected from urine or urinary catheter samples over time (average of 8 isolates per person).
- Genomic analysis focused on genetic relatedness, antimicrobial resistance genes, and virulence factors.
Main Results:
- Most S. aureus strains were multidrug-resistant (MDR), including methicillin-resistant S. aureus (MRSA), predominantly belonging to sequence type 5.
- The same S. aureus strain persisted as ASB for an average of 13 weeks, even with antibiotic treatment and catheter changes.
- In one instance, persistent ASB transitioned to symptomatic CAUTI; longitudinal strains showed minimal genomic variation and stable resistance/virulence profiles.
Conclusions:
- MDR S. aureus can establish long-term persistent ASB in LTUC users, posing a significant clinical challenge.
- Standard strategies for microbial reduction in LTUCs were largely ineffective in eradicating persistent S. aureus ASB.
- Genomic stability of S. aureus strains suggests a resilient pathogen capable of long-term colonization and potential infection.
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