Pathogenesis, Prophylaxis and Treatment of Uropathogenic Infections

A special issue of Pathogens (ISSN 2076-0817).

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 13252

Special Issue Editors


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Guest Editor
Department of Urology, University of California, Los Angeles, CA, USA
Interests: kidney stones; benign prostatic hyperplasia; upper tract urothelial carcinoma; stone pathogenesis and infection; ureteral peristalsis

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Guest Editor
Lewis Katz School of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
Interests: female urology; pelvic pain; neuro-urology

Special Issue Information

Dear Colleagues,

For this Special Issue of Pathogens, we focus on uropathogens. Of particular concern is the rise in the incidence of urosepsis. A recent investigation of the prevalence of sepsis worldwide demonstrated a continuing decline in episodes of sepsis except for patients experiencing urosepsis [1]. Urosepsis is an overwhelming infection that originates in the urinary tract and spreads to the bloodstream, causing substantial morbidity and in some cases mortality. In adults, urosepsis accounts for 25% of all cases of sepsis [2]. 

In this issue, we hope to discuss new insights into the activity of uropathogens and the pathogenesis of urinary tract infections and urosepsis. We welcome a robust discussion of various uropathogens including less common pathogens and the role they may play in the rising numbers of urosepsis as well as the development of urinary tract infections. We look forward to considerations of the changing activity of pathogens in the urinary tract as compared to other areas of the body, new insights into the mechanisms of action of the more commonly recognized uropathogens and the potential role of the various microbiomes.

We recognize the role that the immune response plays in the pathophysiology of urosepsis is substantial and welcome articles on the involvement of cytokines in this process as well as the interplay of other aspects of the immune response.

Clinically, urosepsis occurs primarily due to obstruction or secondary to infected material in the urinary system. This Special Issue will address the clinical correlates of urosepsis, some of the clinical causes of urosepsis, and the identification and management of this disease. Recent work has suggested a connection between current clinical practice and the increasing incidence of urosepsis [3]. We intend for this phenomenon to be addressed.

This issue of Pathogens is expected to incorporate basic research as well as discussions of clinical management. We will end with a discussion of the treatment of urosepsis which must include considerations of early and late diagnosis, new definitions for the classification of sepsis, and an examination of goal-directed therapy and ongoing prevention practices.

References

  1. Kempker, J.A.; Martin, G.S. A global accounting of sepsis. Lancet 2020, 18, 168–170.
  2. Rudd, K.E.; Johnson, S.C.; Agesa, K.M.; Shackelford, K.A.; Tsoi, D.; Kievlan, D.R.; Colombara, D.V.; Ikuta, K.S.; Kissoon, N.; Finfer, S.; et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the Global Burden of Disease Study. Lancet 2020, 18, 200–211.
  3. Wagenlehner, F.M.E.; Bjerklund Johansen, T.E.; Cai, T.; Koves, B.; Kranz, J.; Pilatz, A.; Tandogdu, Z. Epidemiology, definition and treatment of complicated urinary tract infections. Nat. Rev. Urol. 2020, 17, 586–600.

Dr. Kymora B. Scotland
Prof. Dr. Michel A. Pontari
Guest Editors

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Keywords

  • uropathogens
  • urosepsis
  • urinary tract infections
  • microbiome
  • disease management

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Published Papers (5 papers)

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Research

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12 pages, 2195 KiB  
Article
Exploring Condition-Specific Variability in the Ureteral Stent Microbiome
by Ava Mousavi, Karan N. Thaker, James E. Ackerman, Niccole Diaz, Rick Martin, Craig D. Tipton, Nick Tallman, Lina Marcella Henao, Nima Nassiri, Jeffrey Veale, Anne Lenore Ackerman and Kymora B. Scotland
Pathogens 2024, 13(11), 942; https://doi.org/10.3390/pathogens13110942 - 29 Oct 2024
Viewed by 593
Abstract
(1) Background: Indwelling ureteral stents are commonly used urological devices to maintain ureteral patency, yet they have been associated with complications such as infections. Some studies have shown that bacteria adhere to and create an antimicrobial-resistant biofilm on stents. One factor that may [...] Read more.
(1) Background: Indwelling ureteral stents are commonly used urological devices to maintain ureteral patency, yet they have been associated with complications such as infections. Some studies have shown that bacteria adhere to and create an antimicrobial-resistant biofilm on stents. One factor that may impact biofilm formation is the original condition informing stent placement, such as kidney stones and renal allografts. Both kidney stones and renal allografts are independently associated with infection, yet the differential stent microbiomes of these populations remain poorly characterized. Our objective was to characterize these microbiomes in order to inform urological health practice and help prevent ureteral stent-associated infections. (2) Methods: Stents were collected from kidney stone and renal transplant recipients undergoing routine cystoscopic stent removal. Microbial DNA was extracted from stents and analyzed using 16S Next Generation Sequencing. Descriptive statistics, alpha diversity, and beta diversity methods were used for statistical analysis. (3) Results: The microbiome of ureteral stents in kidney stone and transplant patients is composed of unique species, each with different biofilm-forming abilities. (4) Conclusions: Our findings demonstrate that the microbiome of stents differs based on preceding condition. It is important to conduct future studies that explore this microbiome further to understand what type of stent-associated infection someone may develop based on their initial condition. Full article
(This article belongs to the Special Issue Pathogenesis, Prophylaxis and Treatment of Uropathogenic Infections)
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11 pages, 280 KiB  
Article
Clinical Presentation, Microbiological Characteristics, and Their Implications for Perioperative Outcomes in Xanthogranulomatous Pyelonephritis: Perspectives from a Real-World Multicenter Practice
by Vineet Gauhar, José Iván Robles-Torres, Marcelo Langer Wroclawski, Hegel Trujillo-Santamaría, Jeremy Yuen Chun Teoh, Yiloren Tanidir, Abhay Mahajan, Nariman Gadzhiev, Deepak Ragoori, Santosh Kumar, Arvind Ganpule, Pankaj Nandkishore Maheshwari, Luis Roberto García-Chairez, Joana Valeria Enrriquez-Ávila, Juan Francisco Monzón-Falconi, Antonio Esqueda-Mendoza, Juan Pablo Flores-Tapia, Hugo Octaviano Duarte-Santos, Mudasir Farooq, Venkat Arjunrao Gite, Mriganka Mani Sinha, Bhaskar K. Somani and Daniele Castellaniadd Show full author list remove Hide full author list
Pathogens 2023, 12(5), 695; https://doi.org/10.3390/pathogens12050695 - 10 May 2023
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Abstract
Xanthogranulomatous pyelonephritis (XGP) is an uncommon chronic granulomatous infection of renal parenchyma. XGP is often associated with long-term urinary tract obstruction due to stones and infection. We aimed to analyze the clinical, laboratory, and microbial culture profiles from bladder and kidney urine of [...] Read more.
Xanthogranulomatous pyelonephritis (XGP) is an uncommon chronic granulomatous infection of renal parenchyma. XGP is often associated with long-term urinary tract obstruction due to stones and infection. We aimed to analyze the clinical, laboratory, and microbial culture profiles from bladder and kidney urine of patients who were diagnosed with XGP. Databases of patients with histopathological diagnosis of XGP from 10 centers across 5 countries were retrospectively reviewed between 2018 and 2022. Patients with incomplete medical records were excluded. A total of 365 patients were included. There were 228 (62.5%) women. The mean age was 45 ± 14.4 years. The most common comorbidity was chronic kidney disease (71%). Multiple stones were present in 34.5% of cases. Bladder urine culture results were positive in 53.2% of cases. Kidney urine culture was positive in 81.9% of patients. Sepsis and septic shock were present in 13.4% and 6.6% of patients, respectively. Three deaths were reported. Escherichia coli was the most common isolated pathogen in both urine (28.4%) and kidney cultures (42.4%), followed by Proteus mirabilis in bladder urine cultures (6.3%) and Klebsiella pneumoniae (7.6%) in kidney cultures. Extended-spectrum beta-lactamases producing bacteria were reported in 6% of the bladder urine cultures. On multivariable analysis, urosepsis, recurrent urinary tract infections, increased creatinine, and disease extension to perirenal and pararenal space were independent factors associated with positive bladder urine cultures. On multivariable analysis, only the presence of anemia was significantly more frequent in patients with positive kidney cultures. Our results can help urologists counsel XGP patients undergoing nephrectomy. Full article
(This article belongs to the Special Issue Pathogenesis, Prophylaxis and Treatment of Uropathogenic Infections)
12 pages, 3068 KiB  
Article
Development of a High-Throughput Urosepsis Mouse Model
by Roman Herout, Sreeparna Vappala, Sarah Hanstock, Igor Moskalev, Ben H. Chew, Jayachandran N. Kizhakkedathu and Dirk Lange
Pathogens 2023, 12(4), 604; https://doi.org/10.3390/pathogens12040604 - 15 Apr 2023
Cited by 3 | Viewed by 1941
Abstract
Murine sepsis models are typically polymicrobial, and are associated with high mortality. We aimed to develop a high-throughput murine model that mimics a slow-paced, monomicrobial sepsis originating from the urinary tract. A total of 23 male C57Bl/6 mice underwent percutaneous insertion of a [...] Read more.
Murine sepsis models are typically polymicrobial, and are associated with high mortality. We aimed to develop a high-throughput murine model that mimics a slow-paced, monomicrobial sepsis originating from the urinary tract. A total of 23 male C57Bl/6 mice underwent percutaneous insertion of a 4 mm catheter into the bladder using an ultrasound-guided method, previously developed by our group. The following day, Proteus mirabilis (PM) was introduced percutaneously in the bladder in three groups: g1—50 µL 1 × 108 CFU/mL solution (n = 10); g2—50 µL 1 × 107 CFU/mL solution (n = 10); and g3 (sham mice)—50 µL sterile saline (n = 3). On day 4, mice were sacrificed. The number of planktonic bacteria in urine, adherent to catheters, and adherent to/invaded into the bladder and spleen was assessed. Cell-free DNA, D-dimer, thrombin–antithrombin complex (TAT), and 32 pro-/anti-inflammatory cytokines/chemokines were quantified in the blood. All mice survived the 4 day postinterventional period. Mean weight loss was 11% in g1, 9% in g2, and 3% in the control mice. Mean urine CFU counts were highest in group 1. All catheters showed high catheter-adhered bacterial counts. Of the infected mice, 17/20 had CFU counts in the splenic tissue, indicating septicemia. Plasma levels of cell-free DNA, D-dimer, and the proinflammatory cytokines IFN-γ, IL-6, IP-10, MIG, and G-CSF were significantly elevated in infected mice versus controls. We present a reproducible, monomicrobial murine model of urosepsis that does not lead to rapid deterioration and death, and is useful for studying prolonged urosepsis. Full article
(This article belongs to the Special Issue Pathogenesis, Prophylaxis and Treatment of Uropathogenic Infections)
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10 pages, 287 KiB  
Article
Prognosis of Extended-Spectrum-Beta-Lactamase-Producing Agents in Emphysematous Pyelonephritis-Results from a Large, Multicenter Series
by José Iván Robles-Torres, Daniele Castellani, Hegel Trujillo-Santamaría, Jeremy Yuen-Chun Teoh, Yiloren Tanidir, José Gadú Campos-Salcedo, Edgar Iván Bravo-Castro, Marcelo Langer Wroclawski, Santosh Kumar, Juan Eduardo Sanchez-Nuñez, José Enrique Espinosa-Aznar, Deepak Ragoori, Saeed Bin Hamri, Ong Teng Aik, Cecil Paul Tarot-Chocooj, Anil Shrestha, Mohamed Amine Lakmichi, Mateus Cosentino-Bellote, Luis Gabriel Vázquez-Lavista, Boukary Kabre, Ho Yee Tiong, Lauro Salvador Gómez-Guerra, Umut Kutukoglu, Joao Arthur Brunhara Alves-Barbosa, Jorge Jaspersen, Christian Acevedo, Francisco Virgen-Gutiérrez, Sumit Agrawal, Hugo Octaviano Duarte-Santos, Chai Chu Ann, Wei Sien Yeoh and Vineet Gauharadd Show full author list remove Hide full author list
Pathogens 2022, 11(12), 1397; https://doi.org/10.3390/pathogens11121397 - 23 Nov 2022
Cited by 3 | Viewed by 1801
Abstract
Background: Emphysematous pyelonephritis (EPN) is a necrotizing infection of the kidney and surrounding tissues with significant mortality. We aimed to assess the clinical factors and their influence on prognosis in patients being managed for EPN with and without ESBL-producing bacteria and to identify [...] Read more.
Background: Emphysematous pyelonephritis (EPN) is a necrotizing infection of the kidney and surrounding tissues with significant mortality. We aimed to assess the clinical factors and their influence on prognosis in patients being managed for EPN with and without ESBL-producing bacteria and to identify if those with EPN due to ESBL infections fared any different. Methods: A retrospective analysis was performed on patients with EPN diagnosis from 22 centers across 11 countries (between 2013 and 2020). Demographics, clinical presentation, biochemical parameters, radiological features, microbiological characteristics, and therapeutic management were assessed. Univariable and multivariable analyses were performed to determine the independent variables associated with ESBL pathogens. A comparison of ESBL and non-ESBL mortality was performed evaluating treatment modality. Results: A total of 570 patients were included. Median (IQR) age was 57 (47–65) years. Among urine cultures, the most common isolated pathogen was Escherichia coli (62.2%). ESBL-producing agents were present in 291/556 urine cultures (52.3%). In multivariable analysis, thrombocytopenia (OR 1.616 95% CI 1.081–2.413, p = 0.019), and Huang–Tseng type 4 (OR 1.948 95% CI 1.005–3.778, p= 0.048) were independent predictors of ESBL pathogens. Patients with Huang–Tseng Scale type 1 had 55% less chance of having ESBL-producing pathogens (OR 1.616 95% CI 1.081–2.413, p = 0.019). Early nephrectomy (OR 2.3, p = 0.029) and delayed nephrectomy (OR 2.4, p = 0.015) were associated with increased mortality in patients with ESBL infections. Conservative/minimally invasive management reported an inverse association with mortality (OR 0.314, p = 0.001). Conclusions: ESBL bacteria in EPN were not significantly associated with mortality in EPN. However, ESBL infections were associated with poor prognosis when patients underwent nephrectomy compared conservative/minimally invasive management. Full article
(This article belongs to the Special Issue Pathogenesis, Prophylaxis and Treatment of Uropathogenic Infections)

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9 pages, 649 KiB  
Perspective
An Effective Sublingual Vaccine, MV140, Safely Reduces Risk of Recurrent Urinary Tract Infection in Women
by J. Curtis Nickel and R. Christopher Doiron
Pathogens 2023, 12(3), 359; https://doi.org/10.3390/pathogens12030359 - 21 Feb 2023
Cited by 7 | Viewed by 5980
Abstract
Uncomplicated recurrent urinary tract infections (rUTIs) in women are associated with episodic bothersome symptoms and have a significant impact on the mental and physical quality of life. Treatment with antibiotics (short- and long-term dosing) results in acute and chronic side effects and costs [...] Read more.
Uncomplicated recurrent urinary tract infections (rUTIs) in women are associated with episodic bothersome symptoms and have a significant impact on the mental and physical quality of life. Treatment with antibiotics (short- and long-term dosing) results in acute and chronic side effects and costs and promotes general antibiotic resistance. Improved nonantibiotic management of rUTI in women represents a true, unmet medical need. MV140 is a novel sublingual mucosal-based bacterial vaccine developed for the prevention of rUTI in women. Based on observational, prospective, and randomized placebo-controlled studies, MV140 has been shown to safely prevent (or reduce the risk of) UTIs, reduce antibiotic use, overall management costs, and patient burden while improving the overall quality of life in women suffering from rUTIs. Full article
(This article belongs to the Special Issue Pathogenesis, Prophylaxis and Treatment of Uropathogenic Infections)
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