Ureteral Stents Harbor Complex Biofilms With Rich Microbiome-Metabolite Interactions.

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.

Ureteral Stent Encrustation: Epidemiology, Pathophysiology, Management and Current Technology.

PURPOSE: Encrustation is a common phenomenon that can occur following placement of a ureteral stent into the urinary tract, and it can lead to serious complications. The following review addresses the mechanism of encrustation, the management of these stents and the newest technology developed to mitigate this issue. MATERIALS AND METHODS: We performed a comprehensive literature search on stent encrustation including peer-reviewed publications, public product listings, and material on current and future stent technology. RESULTS: The mechanism of encrustation is complex and multifaceted, including dwell time, patient specific risk factors, conditioning film formation, biofilm formation and mineral deposition. Several technological developments in stent materials and coatings may have a role in reducing the risk of stent encrustation. It is important to identify the extent of stent encrustation and plan treatment strategies accordingly. We propose a novel treatment algorithm for the management encrusted ureteral stents. CONCLUSIONS: The ubiquity of ureteral stents in urology practice mandates updated knowledge about the prevention of stent encrustation, identification of high risk patients and preparedness for removal using multimodal techniques.

Risk of Urinary Tract Infection Symptoms after Posthysterectomy Cystoscopy with 50% Dextrose as Compared with Saline Cystoscopy with Indigo Carmine.

STUDY OBJECTIVE: Compare odds of postoperative urinary symptoms in women who had cystoscopy after benign laparoscopic hysterectomy with 50% dextrose and with normal saline solution with intravenous indigo carmine. DESIGN: Retrospective cohort study. SETTING: Two tertiary care centers. PATIENTS: All women who underwent benign laparoscopic hysterectomy and intraoperative cystoscopy carried out by a single surgeon. INTERVENTIONS: We compared postoperative urinary symptoms in patients who received 50% dextrose cystoscopy fluid (January 2016-June 2017) with those who received saline cystoscopy with intravenous indigo carmine (November 2013-April 2014). MEASUREMENTS AND MAIN RESULTS: A total of 96 patients had cystoscopy with 50% dextrose and 104 with normal saline with intravenous indigo carmine. Differences in baseline characteristics of the two groups of participants mainly reflected institutional population diversity: age (45.2 vs 41.9, p = .01), body mass index (26.9 vs 33.4, p <.01), race, current smoking status (1% vs 7.8%, p = .04), diabetes (2.1% vs 11.5%, p = .01), history of abdominal surgery (53.1% vs 74%, p <.01), hysterectomy type, receipt of intraoperative antibiotics (92.7% vs 100%, p <.01), recatheterization (10.4% vs 0%, p <.01), and removal of catheter on postoperative day 0 (66.7% vs 12.5%, p <.01). Urinary symptoms were similar for 50% dextrose and saline (12.5% vs 7.7%, p = .19). After adjusting for age, body mass index, race, diabetes, and day of catheter removal, there remained no significant differences in urinary symptoms between the groups (odds ratio 3.19 [95% confidence interval, 0.82-12.35], p = .09). One immediate bladder injury was detected in the saline group and 1 delayed lower urinary tract injury in the 50% dextrose group. CONCLUSION: Overall, most women experienced no urinary symptoms after benign laparoscopic hysterectomy. There were no significant differences in postoperative urinary symptoms or empiric treatment of urinary tract infection after the use of 50% dextrose cystoscopy fluid as compared with normal saline. The previous finding of increased odds of urinary tract infection after dextrose cystoscopy may be due to use in a high-risk population.

Detection of microbial colonization of the urinary tract of patients prior to secondary ureterorenoscopy is highly variable between different types of assessment: results of a prospective observational study.

This study compares the findings of different detection methods for microorganisms in patients with ureteral stents undergoing secondary ureterorenoscopy including the use of a novel validated examination pipeline for biofilms on ureteral stents. Of the included 94 patients, 21.3% showed bacteriuria in preoperative urine cultures. Intraoperative urine culture showed bacteriuria in four (4.3%) of the patients. Stent biofilm cultures were positive in 12.9% and qPCR detected bacterial DNA in 18.1%. The findings of the different examinations were poorly correlated with each other. Detection of microorganisms in the urinary tract of patients with indwelling ureteral stents is highly dependent on timing (i.e. pre- vs intraoperative) and method of assessment. Preoperative routine urine cultures are not predictive for intraoperative urine- and stent culture. These results cast doubt on the clinical relevance of enterococcal species, staphylococci, and streptococci if identified preoperatively prior to stent removal. The timing of oral preoperative antibiotic prophylaxis might need to be reconsidered.

Pathological changes and bacteriological assessments in the urinary tract of pregnant goats experimentally infected with Brucella melitensis.

BACKGROUND: This study was conducted to investigate the pathological changes and distribution of B. melitensis in the urinary tract of pregnant goats following acute experimental infection. Six Jamnapari crossbred does in their third trimester of pregnancy were randomly assigned into two groups; Group 1 was uninfected control and Group 2 was inoculated conjunctival with 0.1 mL of the inoculums containing 109 cfu/mL of live B. melitensis. All does were sacrificed 30 days post-inoculation before the kidney, ureter, urinary bladder, urethra and vaginal swab were collected for isolation of B. melitensis. The same tissue samples were fixed in 10% neutral buffered formalin for hematoxylin and eosin, and immunoperoxidase staining. RESULTS: None of the goats showed clinical signs or gross lesions. The most consistent histopathology finding was the infiltration of mononuclear cells, chiefly the macrophages with few lymphocytes and occasionally neutrophils in all organs along the urinary tract of the infected goats of Group 2. Other histopathology findings included mild necrosis of the epithelial cells of the renal tubules, congestion and occasional haemorrhages in the various tissues. Kidneys showed the most severe lesions. Immunoperoxidase staining revealed the presence of B. melitensis within the infiltrating macrophages and the epithelium of renal tubules, ureter, urethra and urinary bladder. Most extensive distribution was observed in the urinary bladder. Brucella melitensis was successfully isolated at low concentration (3.4 × 103 cfu/g) in the various organs of the urinary tract and at high concentration (2.4 × 108 cfu/mL) in the vaginal swabs of all infected goats. Although B. melitensis was successfully isolated from the various organs of the urinary tract, it was not isolated from the urine samples that were collected from the urinary bladder at necropsy. CONCLUSION: This study demonstrates the presence of low concentrations of B. melitensis in the organs of urinary tract of pregnant does, resulting in mild histopathology lesions. However, B. melitensis was not isolated from the urine that was collected from the urinary bladder.

Surface immobilization of kanamycin-chitosan nanoparticles on polyurethane ureteral stents to prevent bacterial adhesion.

Bacterial adhesion is a major problem that can lead to the infection of implanted urological stents. In this study, kanamycin-chitosan nanoparticles (KMCSNPs) were immobilized on the surface of a polyurethane ureteral stent (PUS) to prevent urinary bacterial infection. KMCSNPs were synthesized using the ionic gelation method. The synthesized KMCSNPs appeared spherical with a ζ-average particle size of 225 nm. KMCSNPs were immobilized on the PUS surface by covalent immobilization techniques. The surface-modified PUS was characterized using attenuated total reflectance Fourier transform infrared spectroscopy, field emission scanning electron microscopy, and energy dispersive X-ray spectroscopy. The surface-modified PUS showed significantly increased antibacterial activity against Escherichia coli MTCC 729 and Proteus mirabilis MTCC 425 relative to the surface of an unmodified PUS. These findings suggest that the KMCSNP-immobilized PUS has the potential to prevent bacterial infection in the human urinary tract.

Understanding urinary conditioning film components on ureteral stents: profiling protein components and evaluating their role in bacterial colonization.

Ureteral stents are fraught with problems. A conditioning film attaches to the stent surface within hours of implantation; however, differences between stent types and their role in promoting encrustation and bacterial adhesion and colonization remain to be elucidated. The present work shows that the most common components do not differ between stent types or patients with the same indwelling stent, and contain components that may drive stent encrustation. Furthermore, unlike what was previously thought, the presence of a conditioning film does not increase bacterial adhesion and colonization of stents by uropathogens. Genitourinary cytokeratins are implicated in playing a significant role in conditioning film formation. Overall, stent biomaterial design to date has been unsuccessful in discovering an ideal coating to prevent encrustation and bacterial adhesion. This current study elucidates a more global understanding of urinary conditioning film components. It also supports specific focus on the importance of physical characteristics of the stent and how they can prevent encrustation and bacterial adhesion.

Escherichia coli-mediated impairment of ureteric contractility is uropathogenic E. coli specific.

BACKGROUND: Ureters are fundamental for keeping kidneys free from uropathogenic Escherichia coli (UPEC), but we have shown that 2 strains (J96 and 536) can subvert this role and reduce ureteric contractility. To determine whether this is (1) a widespread feature of UPEC, (2) exhibited only by UPEC, and (3) dependent upon type 1 fimbriae, we analyzed strains representing epidemiologically important multilocus sequence types ST131, ST73, and ST95 and non-UPEC E. coli. METHODS: Contractility and calcium transients in intact rat ureters were compared between strains. Mannose and fim mutants were used to investigate the role of type 1 fimbriae. RESULTS: Non-UPEC had no significant effect on contractility, with a mean decrease after 8 hours of 8.8%, compared with 8.8% in controls. UPEC effects on contractility were strain specific, with decreases from 9.47% to 96.7%. Mannose inhibited the effects of the most potent strains (CFT073 and UTI89) but had variable effects among other UPEC strains. Mutation and complementation studies showed that the effects of the UTI89 cystitis isolate were fimH dependent. CONCLUSIONS: We find that (1) non-UPEC do not affect ureteric contractility, (2) impairment of contractility is a common feature of UPEC, and (3) the mechanism varies between strains, but for the most potent UPEC type 1 fimbriae are involved.

Effect of co-trimoxazole and N-acetylcysteine alone and in combination on bacterial adherence on ureteral stent surface.

To assess the effect of co-trimoxazole and N-acetylcysteine (NAC), alone and in combination, on bacterial adherence to biofilm formed on ureteral stent surfaces. This prospective randomized study was conducted on 636 patients who underwent double J ureteral stent insertion after variable urological procedures. Patients were randomized into four groups: A (n = 165), no antibiotics or mucolytics during stent indwelling; B (n = 153), oral NAC (200 mg/day for children aged < 12 years old and 600 mg/day for adults) during stent indwelling; C (n = 162), oral co-trimoxazole (2 mg TMP/kg/day) during stent indwelling; and D (n = 156), both oral NAC and co-trimoxazole during stent indwelling. Two weeks following double J stent (JJ stent) insertion, urinalysis was performed on all patients and urine culture was done for all the patients at the day of double J stent removal. The stent was removed 2 weeks postoperatively, and a stent segment sized 3-5 cm from the bladder segment of the stent was sent for culture. Positive stent cultures were found in 63.6% (105/165), 43.1% (66/153), 37% (60/162), and 19.2% (30/156) patients of groups A, B, C, and D, respectively. E. coli was the organism most commonly isolated from the stent culture in all groups. The combination of co-trimoxazole and NAC was more effective in reducing bacterial adherence on ureteral stent surfaces than either alone.

Efficacy of tigecycline and rifampin alone and in combination against Enterococcus faecalis biofilm infection in a rat model of ureteral stent.

BACKGROUND: We investigated the efficacy of tigecycline and rifampin alone or combined in preventing ureteral stent infection due to Enterococcus faecalis. MATERIALS AND METHODS: The activities of the two antibiotics were previously studied in vitro in absence or in presence of biofilm. For in vivo research, the study included a control group without bacterial challenge to evaluate the sterility of surgical procedure, a challenged control group that did not receive any antibiotic prophylaxis and, for each bacterial strain, three challenged groups that received: (1) 2 mg/kg intraperitoneal tigecycline, immediately after stent implantation; (2) rifampin-coated ureteral stents where 0.2 cm(2) sterile ureteral stents were incubated in 10 mg/L rifampin solution for 30 min immediately before implantation; and (3) intraperitoneal tigecycline plus rifampin-coated ureteral stent at the above concentrations. Ureteral stents were explanted at d 5 following implantation and biofilm bacteria enumerated. RESULTS: The in vitro studies showed that the biofilm was strongly affected by the presence of rifampin and, in its presence, tigecycline had MICs and MBCs lower than those obtained in the absence of rifampin. Intraperitoneal tigecycline exerted stronger effect than rifampin on bacterial numbers. The combination rifampin plus tigecycline showed efficacies higher than that of each single compound. CONCLUSION: These results highlight the potential usefulness of tigecycline in preventing enterococcal ureteral stent infections and the role of rifampin as an interesting antibiotic enhancer.

Effect of uropathogens on in vitro encrustation of polyurethane double J ureteral stents.

Polyurethane stents are used when there is an obstruction to the flow of urine. A majority of the patients with such stents are at the risk of urinary tract infection and salt encrustation. The present study is aimed at analyzing the in vitro encrustation of calcium oxalate and other salts in the presence of common uropathogens (E. coli and P. mirabilis) on films made from Tecoflex(®), a commercial grade polyurethane. In the absence of uropathogens, sodium ions and ammonia favor calcium adsorption whereas magnesium ions greatly depress it, resulting in increased hydrophillicity of the stent. With E. coli, Mg ions enhance the encrustation of calcium, whereas the other salts decrease its deposition. In case of P. mirabilis, irrespective of the type of salt, it enhances calcium encrustation except in the presence of sodium ions. Adhesion of uropathogens to the stent surface was higher in the presence of bovine serum albumin. Understanding the dynamics between various salts and microorganism in the urine, and urine-stent interface would aid in designing stents that are inert, resist encrustation and biofilm formation.

Processing human urine and ureteral stents for 16S rRNA amplicon sequencing.

Ureteral stents are commonly used medical devices that harbor a unique and patient-specific microbial community. This protocol describes an optimized procedure for high-quality DNA extraction from both urine and ureteral stent samples for the purpose of downstream microbiota characterization by amplicon sequencing. Detailed instruction is provided for 16S rRNA gene V4 region sequencing with the Illumina platform, which enables accurate and reproducible microbiota profiling of low bacterial abundance urine and stent samples. For complete details on the use and execution of this protocol, please refer to Al et al. (2020).

Surface analysis of ureteral stent before and after implantation in the bodies of child patients.

The aim of this work was to determine which part of a double-J ureteral stent (DJ stents) showed the highest tendency to crystal, calculi, and biofilm deposition after ureterorenoscopic-lithotripsy procedure (URS-L) to treat calcium oxalate stones. Additionally, the mechanical strength and the stiffness of DJ stents were evaluated before and after exposure to urine. Obtained results indicated that the proximal (renal pelvis) and distal (urinary bladder) part is the most susceptible for post-URS-L fragments and urea salt deposition. Both, the outer and inner surfaces of the DJ ureteral stents were completely covered even after 7 days of implantation. Encrustation of DJ stents during a 31-day period results in reducing the Young's modulus by 27-30%, which confirms the loss of DJ stent elasticity and increased probability of cracks or interruption. Performed analysis pointed to the need to use an antibacterial coating in the above-mentioned part of the ureteral stent to prolong its usage time and to prevent urinary tract infection.

Xanthogranulomatous Ureteritis Mimicking Ureteral Involvement by Cancer in a Radical Cystectomy Specimen.

Xanthogranulomatous pyelonephritis is well established as a renal mass-forming inflammatory process. However, a ureteral counterpart is minimally recognized. In this article, we present a case of xanthogranulomatous ureteritis in an 81-year-old woman, mimicking ureteral involvement by cancer in a radical cystectomy specimen for invasive urothelial carcinoma. Similar to the pathogenesis of xanthogranulomatous pyelonephritis, the patient was noted to have ureteral obstruction by calculus and had urine culture positive for Klebsiella pneumoniae. To our knowledge, this is the first report of xanthogranulomatous ureteritis associated with this pathogen and the only report associated with concurrent bladder cancer. Increased pathologist and urologist awareness of xanthogranulomatous ureteritis expands the spectrum of pseudotumoral processes of the ureter.

A noninvasive renal fungus ball caused by Rhizopus--a previously unreported manifestation of zygomycosis.

We describe the first reported case of renal zygomycosis presenting as an isolated fungus ball (bezoar) without renal parenchymal invasion. Since all previous descriptions of renal involvement have discussed tissue invasion, our case is unique in that the infection was confined solely in the renal pelvis and extended to the distal ureter without signs of contiguous renal infection. Our patient later developed renal insufficiency while receiving amphotericin B Lipid Complex (ABLC). The therapy was changed to posaconazole with subsequent clinical, mycologic, and radiographic improvement and the patient has remained free of recurrence 5 years after diagnosis.

Ureteral Stent Microbiota Is Associated with Patient Comorbidities but Not Antibiotic Exposure.

Ureteral stents are commonly used to prevent urinary obstruction but can become colonized by bacteria and encrusted, leading to clinical complications. Despite recent discovery and characterization of the healthy urinary microbiota, stent-associated bacteria and their impact on encrustation are largely underexplored. We profile the microbiota of patients with typical short-term stents, as well as over 30 atypical cases (all with paired mid-stream urine) from 241 patients. Indwelling time, age, and various patient comorbidities correlate with alterations to the stent microbiota composition, whereas antibiotic exposure, urinary tract infection (UTI), and stent placement method do not. The stent microbiota most likely originates from adhesion of resident urinary microbes but subsequently diverges to a distinct, reproducible population, thereby negating the urine as a biomarker for stent encrustation or microbiota. Urological practice should reconsider standalone prophylactic antibiotics in favor of tailored therapies based on patient comorbidities in efforts to minimize bacterial burden, encrustation, and complications of ureteral stents.

Dapagliflozin-associated euglycemic diabetic ketoacidosis in a patient with type 2 diabetes mellitus: A case report.

RATIONALE: Rare cases of euglycemic diabetic ketoacidosis (eu-DKA) have been reported after the administration of sodium-glucose cotransporter-2 (SGLT-2) inhibitors. No reports have described eu-DKA complicated by hypernatremia due to SGLT-2 inhibitors. PATIENT CONCERNS: A 76-year-old woman with a 40-year history of type 2 diabetes mellitus (DM), for which metformin (1000 mg/day) and dapagliflozin (10 mg/day) were prescribed, presented with malaise, fever, and oliguria. On presentation, her white blood cell count (11,800/µL), serum creatinine (3.2 mg/dL), and C-reactive protein (54 mg/L) were abnormal. Bilateral pyeloureteritis and diffuse paralytic ileus were present. She received intravenous antibiotics and total parenteral nutrition, and was asked to fast. Her renal function and ileus briefly improved. Oral hypoglycemic agents, metformin and dapagliflozin, along with enteral feeding were reinstituted on day 3 of hospitalization. However, on day 6 of hospitalization, the patient developed an altered state of consciousness including confusion, lethargy, and stupor. Several laboratory abnormalities suggestive of ketoacidosis with euglycemia were noted. DIAGNOSES: The patient was diagnosed with eu-DKA accompanied by severe hypernatremia (corrected serum Na concentration, 163 mEq/L) and hypokalemia following dapagliflozin re-administration. INTERVENTIONS: The patient was treated with indicated intravenous fluid therapy. Dapagliflozin use was discontinued. OUTCOMES: The patient's mental status and laboratory findings improved gradually, and she was discharged on maintenance doses of insulin and metformin on day 14 of hospitalization. LESSONS: Acute illnesses such as diffuse paralytic ileus and urinary tract infection, and dietary restrictions or fasting in patients with DM can be considered potential predisposing factors for SGLT-2 inhibitor-associated eu-DKA. For patients with diabetes in the setting of acute morbidity, timely resumption of the SGLT-2 inhibitor therapy should be carefully determined. In addition, eu-DKA due to SGLT-2 inhibitor use may be accompanied by electrolyte disturbances such as hypernatremia and hypokalemia.

The 'buoy' stent: evaluation of a prototype indwelling ureteric stent in a porcine model.

OBJECTIVE To assess a prototype ureteric 'buoy' stent with a 10 F upper body tapering to a 3F tail, developed to potentially reduce stent-related irritative symptoms while providing an adequate mould for healing after endopyelotomy. MATERIALS AND METHODS Eighteen Yucatan minipigs had the stent placed either into the intact ureter (phase I) or after Acucise proximal endoureterotomy (phase II). Buoy stents were compared to 10/7 F endopyelotomy stents and to standard 7 F stents in phases I and II, respectively. The pigs were assessed for vesico-ureteric reflux, hydronephrosis and infection, before stent insertion and at harvest. Stents were weighed before and after placement and the removal force was measured. Pressure/flow studies, antegrade nephrostograms and specimens for histopathology from the renal pelvis, ureter and vesico-ureteric junction (VUJ) were obtained at harvest. RESULTS Thirteen minipigs survived the entire study. Ureteric flow with the stents in situ was better for buoy stents than for 10/7 F stents (P < 0.005). Ureteric flow after endoureterotomy and subsequent stent removal was similar for buoy stents and standard 7 F stents. None of the stents refluxed. There was no difference between stents in removal force, weight change or incidence of hydronephrosis. At 1 and 12 weeks, buoy stents tended to produce lower histopathological alteration scores than control stents, especially at the VUJ (phase I, 2.0 vs 3.9, P = 0.092; phase II, 0.6 vs 1.7, P = 0.18). CONCLUSIONS The novel buoy stents are easily placed and removed via the urethra. They can cause less VUJ inflammation than standard stents while allowing for adequate ureteric flow and healing after proximal endoureterotomy.

Ureteric schistosomiasis with obstructive uropathy.

A 25-year-old male Nigerian undergraduate who had earlier been treated with praziquantel for schistosomal epidydymitis presented with clinical features of pyelonephritis, and radiological appearances of bilateral hydroureteronephrosis with fibrosis of lower ureters. Surgical resection of the ureters, Boari flap and Psoas hitch reconstruction were done. The histology of the resected ureters proved schistosomiasis. He was subsequently treated with praziquantel and artemether. This case highlights the insidious nature of schistosomiasis infection, possibility of progression of primary infection with complications or probable reinfection in a previously treated individual. In any case, surgical intervention may be necessary in those who present late with severe ureteric stricture and also to prevent progressive renal damage.