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JU INSIGHT Ureteral Stents Harbor Complex Biofilms With Rich Microbiome-Metabolite Interactions

By: Glenn T. Werneburg, MD, PhD, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Ohio; Daniel Hettel, MD, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Ohio; Scott D. Lundy, MD, PhD, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Ohio; Ava Adler, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Ohio; Smita De, MD, PhD, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Ohio; Sromona D. Mukherjee, PhD, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Ohio; Raymond R. Rackley, MD, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Ohio; Daniel A. Shoskes, MD, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Ohio; Aaron W. Miller, PhD, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Ohio | Posted on: 18 May 2023

Werneburg GT, Hettel D, Lundy SD, et al. Ureteral stents harbor complex biofilms with rich microbiome-metabolite interactions. J Urol. 2023;209(5):950-962.

Study Need and Importance

Ureteral stents, used to drain the upper urinary tract or facilitate healing, can be associated with encrustation and infection. Biofilms, structures of bacteria adherent to one another and a surface, commonly form on stents. Biofilm formation has been implicated in stent-associated urinary tract infection and encrustation, but biofilms also form in the absence of these phenomena. Understanding the relationship between stent biofilm composition and infection or encrustation may lead to optimization of materials and strategies to reduce biofilm and stent-related complications.

What We Found

All ureteral stents harbored microbial biofilms, even in the absence of infection. Specific microbial genera were more abundant in samples from stents where there was antibiotic exposure during indwelling time (Escherichia/Shigella, Pseudomonas, Staphylococcus, Ureaplasma) and in those associated with infection (Escherichia/Shigella, Ureaplasma). The antibiotic resistance genes sul2 (sulfonamide resistance) and ampC (beta-lactamase) were detected in 65.7% and 97.1% of stents tested for resistance, respectively. Strains identified as clinically relevant and central to microbe-metabolite interaction networks were analyzed using a CDC continuous-flow stir tank bioreactor, a large culture environment designed to mimic the urinary tract with an indwelling ureteral stent. All strains analyzed in the bioreactor reconstituted biofilm, with differential formation by strain (Enterococcus faecalis most) and material type (see Figure).

Figure. Scanning electron microscopy reveals biofilm formation on multiple strains and material types. Each strain was grown in a continuous-flow stir-tank bioreactor for 72 hours along with a series of coupons of different material types. Material types are indicated to the left of each row. Escherichia coli is indicated in the left column and Enterococcus faecalis is indicated in the center column. The negative control, wherein coupons were incubated in the bioreactor together with sterile media, is shown in the right column. Blue arrows indicate bacteria, yellow arrows indicate matrix components, and white arrows indicate abiotic crystals. Microbial size and morphology are indicated on the top of each column. Scale bars are indicated on the respective micrographs. Micrographs of all tested strains and materials are shown in Supplemental Figure 6, and quantitative analyses of biofilm are shown via plate count assay in Figure 5 of the manuscript. EHT indicates electron high tension; Mag, magnification; PTFE, polytetrafluoroethylene; WD, working distance.

Limitations

Limitations of the study include the small sample size of stents associated with infection and lack of stratification of stents by model and composition.

Interpretation for Patient Care

Biofilms are uniformly present on stents and exhibit patterns unique to infection and recent antibiotic use. Microbes isolated from stents reconstituted biofilm formation in vitro, and thus novel material types and coatings may now be tested for anti-biofilm properties, and commensal strains tested for bacterial interference properties against pathogens. The findings and techniques may be generalizable to other indwelling medical devices within and outside urology.

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