Microbial co-occurrences on catheters from long-term catheterized patients

This study determines the positive and negative microbial co-occurrences between uropathogenic species in the lower urinary tract microenvironment of long-term catheterized patients.
Published in Microbiology
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Catheter-associated urinary tract infections (CAUTIs) are among the most common cause of healthcare-associated infections (HAIs), affecting over 1 million cases annually in the United States1. It is estimated that 75% of healthcare-acquired UTIs are associated with catheterization, and the risk of bacterial colonization of a catheter increases 3–7% per day upon placement which results in near 100% colonization in long-term catheterized patients. CAUTIs are caused by a diverse range of pathogens, including UPEC (23.9%), fungal Candida spp. (17.8%), Enterococcus spp. (13.8%), P. aeruginosa (10.3%), Klebsiella sp. (10.1%), etc., which are increasingly becoming antibiotic resistant2. One major factor complicating the treatment of CAUTIs is the high prevalence of polymicrobial colonization, with 31–87% of catheters and urine from catheterized patients identified with the colonization by two or more species. Polymicrobial CAUTIs are associated with increased mortality relative to infections by a single uropathogen, while relationships between the bacteria in these polymicrobial communities are still poorly understood3,4.

In this study, we collected and analyzed voided urine and catheters samples from 55 long-term catheterized patients that were collected monthly over a year for determining microbial community composition in the lower urinary tract environment. For all collected samples, we detected two or more species in ~80.1% (296/366) of samples in both urine and catheter samples at each time point, concordant with previous reports that the majority of CAUTIs are polymicrobial3,4. Moreover, while each patient was colonized by 6–7 species over the whole collection periods, only 2–3 unique species were identified at a single collection period. Of note, one limitation of this work is the use of a culture-based approach that may lose the detection of fastidious and anaerobic species and limit the species to be included in the subsequence 16S rRNA sequencing and downstream analyses. Future studies are necessary to bridge the gap between standard clinical techniques for microbial detection and newer sequencing-based approaches that are not currently used in the clinical setting.

Secondly, by analyzing the antibiotic treatment record of our patient cohort over the course of the study, we found that most patients (40/55, 72.7%) received at least one antibiotic and nearly 50% (27/55) patients received more than one type of antibiotic. The most prescribed antibiotics included those commonly or specifically used to treat urinary tract infections, e.g., nitrofurantoin, methenamine, ciprofloxacin, and the combination of trimethoprim and sulfamethoxazole, etc. Furthermore, we noticed that despite recurrent antibiotic treatments, mono- and poly-microbial species were still observed to persistently colonize the implanted catheters, raising the concern of increasing antibiotic resistance for uropathogens. Together, these findings suggest that long-term catheterized patients may be at increased risk of developing antibiotic-resistant infections, and that further understanding the composition of these communities may aid in the development of novel strategies to develop effective therapeutics.

Lastly, we aimed to determine the positive and negative associations between different bacterial species within the polymicrobial community by performing a co-occurrence analysis to identify the pairwise genera that had positive and negative co-occurrences. We were able to detect positive co-occurrences between several pairs of genera, including Klebsiella with Pseodomonas and Enterococcus, Candida with Serratia, Providencia with Pseudomonas and Serratia, Morganella with Alcaligenes, and Aerococcus with Enterobacter. Of note, Staphylococcal species were observed to repel the co-existence with both Gram-positive and Gram-negative pecies, demonstrating the most negative associations with other bacterial species. To further characterize the bacterial interactions that facilitate co-colonization, we examined the bacterial growth of two species using a co-culture system and found that E. faecalis growth was significantly augmented in the mixed cultures with E. coli, K. pneumoniae, and P. aeruginosa. Our findings suggest that mutually beneficial interactions between different bacterial species in the polymicrobial community may lead to polymicrobial CAUTI. This opens the avenue for further investigation to study the molecular drivers of these interactions for insights to perturb the formation and stability of problematic polymicrobial infections in CAUTI.

We are committed to further investigating and deciphering the polymicrobial community in CAUTI. We welcome feedback and suggestions from readers.

References

1         Magill, S. S. et al. Changes in Prevalence of Health Care-Associated Infections in U.S. Hospitals. N Engl J Med 379, 1732-1744, doi:10.1056/NEJMoa1801550 (2018).

2         Flores-Mireles, A., Hreha, T. N. & Hunstad, D. A. Pathophysiology, Treatment, and Prevention of Catheter-Associated Urinary Tract Infection. Top Spinal Cord Inj Rehabil 25, 228-240, doi:10.1310/sci2503-228 (2019).

3         Hola, V., Ruzicka, F. & Horka, M. Microbial diversity in biofilm infections of the urinary tract with the use of sonication techniques. FEMS Immunol Med Microbiol 59, 525-528, doi:10.1111/j.1574-695X.2010.00703.x (2010).

4         Armbruster, C. E., Brauer, A. L., Humby, M. S., Shao, J. & Chakraborty, S. Prospective assessment of catheter-associated bacteriuria clinical presentation, epidemiology, and colonization dynamics in nursing home residents. JCI Insight 6, doi:10.1172/jci.insight.144775 (2021).

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