Ureteral Stents Harbor Complex Biofilms With Rich Microbiome-Metabolite Interactions

Abstract

Purpose:We sought to determine microbe-metabolite composition and interactions within indwelling ureteral stent biofilms, determine their association with patient factors including infection, and reconstitute biofilm formation on relevant surface materials in vitro.Materials and Methods:Upon ureteral stent removal from patients, proximal and distal ends were swabbed. Samples were analyzed by 16S next-generation sequencing and metabolomics. A continuous-flow stir-tank bioreactor was used to reconstitute and quantify in vitro biofilm formation from stent-isolated bacteria on stent-related materials including silicone, polytetrafluoroethylene, polyurethane, polycarbonate, and titanium. Diversity, relative abundance, and association with clinical factors were analyzed with ANOVA and Bonferroni t-tests or PERMANOVA. Biofilm deposition by microbial strain and device material type were analyzed using plate counts and scanning electron microscopy following bioreactor incubation.Results:All 73 samples from 37 ureteral stents harbored microbiota. Specific genera were more abundant in samples from stents wherein there was antibiotic exposure during indwelling time (Escherichia/Shigella, Pseudomonas, Staphylococcus, Ureaplasma) and in those associated with infection (Escherichia/Shigella, Ureaplasma). The enriched interaction subnetwork in stent-associated infection included Ureaplasma and metabolite 9-methyl-7-bromoeudistomin. Strains identified as clinically relevant and central to interaction networks all reconstituted biofilm in vitro, with differential formation by strain (Enterococcus faecalis most) and material type (titanium least).Conclusions:Ureteral stent biofilms exhibit patterns unique to stent-associated infection and antibiotic exposure during indwelling time. Microbes isolated from stents reconstituted biofilm formation in vitro. This work provides a platform to test novel materials, evaluate new coatings for anti-biofilm properties, and explore commensal strain use for bacterial interference against pathogens.

This Month in Adult Urology

“…Finally, Werneburg et al (page 950) from Cleveland, Ohio investigate microbiome within the biofilms covering indwelling ureteral stents. 8 Samples of stents removed from patients were analyzed by 16S next-generation sequencing and metabolomics. The authors report that all samples harbored microbiota with associations with previous antibiotic exposure.…”

Leading Antimicrobial Stewardship From the Operating Room

“…Finally, in a recent article by Werneburg et al on biofilms formed on ureteral stents, the authors found that patients with prolonged antibiotic use beyond single-dose periprocedural prophylaxis in the presence of indwelling stents had more associated uropathogens and less protective commensal microbiota in their stent biofilms. 10 Although this was a small translational study including samples from only 37 patients, it demonstrates the profound impact that antibiotics can have on microbe speciation and antimicrobial sensitivity at the individual patient level.…”

Reply by Authors

“…In line with the former theory, Lactobacillus was less abundant in stent biofilms from males and females with a history of antibiotic exposure during stent indwelling time (Supplemental Figure 4, B in article, https://www.jurology.com). 1 A reduction of Lactobacillus and other protective microbiota by antibiotics may have allowed uropathogens to establish a foothold for colonization. Lactobacillus is the most abundant commensal bladder genus, and among the most commonly detected genera in stent biofilms in the present study.…”

“…Ureteral stent biofilms from those with antibiotic exposure during stent indwelling time harbored greater abundance of Escherichia , Pseudomonas , Staphylococcus, and Ureaplasma than those without associated antibiotic exposure (Figure 3, B in article). 1 One theory accounting for this is disruption of commensal urinary tract flora by antibiotics, thus facilitating uropathogen colonization. An alternative theory is that individuals whose stents harbored uropathogens may have had symptoms of stent-associated urinary tract infection, and thus were prescribed antibiotics.…”