Talking to Your Doctor About Chronic UTI 

Whether you’re new to the world of persistent lower urinary tract symptoms (LUTS) or you’ve been dealing with them long enough to consider yourself an expert at-home UTI researcher, you’ve likely sought out reliable information to share with your doctor. 

But quality resources around this topic can be difficult to find. This is why we developed materials that provide actionable information and encourage discussion between you and your clinician. Via the tools listed above, you can access a testing directory, evidence-based research to share with your clinician, and a guide to encourage communication. 

It’s important that any information shared with busy clinicians is based on peer reviewed research and is quick to read.

We’ve taken all of this into consideration while developing the ‘Take to Your Doctor’ materials. Written in partnership with our medical and research advisors, we’ve collected and summarized some of the most impactful studies around UTI and presented them in an easy to navigate format. 

How to use the directory and resource

Causes of persistent UTI are rarely straightforward. This is why the directory highlights testing types available through US and UK laboratories that specialize in enhanced testing methods. 

These include tests for UTI, vaginal imbalances, and prostatic abnormalities. 

You can get started now or continue reading to learn more about updates to the 2024 directory. 

Most exciting for many in our community who have struggled to access tests without a clinician’s signature – the addition of labs who provide a direct-to-patient ordering option. 

You can quickly identify the labs offering these testing types and services by viewing the codes within each listing. 

How to Get Started

1. Download the clinician resource
2. Download the patient guide for sharing these resources with your clinician
3. Download the testing directory: covering UTI, vaginal, and prostate tests
4. Watch Understanding the UTI Clinician Resource
5. Watch How to use the patient guide and worksheet

Thank you for taking an active role in educating others about persistent and difficult to diagnose UTIs and would love to hear about your experience with these resources. You can reach out to us directly. 

If you’ve found this information helpful, you can support further education efforts and other projects by contributing to the work that means the most to you.

Excerpts from Improving Treatment Pathways for Patients with Persistent Lower Urinary Tract Symptoms

New for 2023

Understanding the vaginal and urinary microbiome connection

• While the microbiomes of the urinary tract and bladder are unique, there is significant overlap between the species and protein functions of the two environments, giving way to the theory that they could be considered one single urogenital microbiome.⁵ 
• For women with vaginal dysbiosis, there exists an increased risk of developing a UTI compared to women with a Lactobacillus-dominated vaginal microbiome.³⁷ 

75%, 46%, and 13% of women with bacterial vaginosis, candidiasis, or trichomoniasis respectively, also have a UTI.³⁸

2022

Current Research into the Bladder Microbiome

• Bacterial communities have been observed in 80% of samples obtained by transurethral catheter of female participants, with up to 92% of the samples being reported as ‘no growth’ using SUC.¹ A dysbiosis of this healthy urinary microbiome (the urobiome) is correlated with the development of symptoms and urinary disorders.^1-3
• Participants with urinary symptoms demonstrated a more diverse urobiome with larger quantities of bacteria than asymptomatic controls. The frequency of bacterial detection was between 81% and 86% for symptomatic cohorts compared to only 57% in the control cohort.^1,2,4,5
• When compared with asymptomatic controls, patients experiencing urgency incontinence had statistically significant differences in their urobiome, with lower levels of Lactobacillus and higher levels of Gardnerella.^6,7,8

Evidence of Polymicrobial Infection

• The limited capabilities and E. coli-centric bias of standard urine culture (SUC) has been well established. SUC identifies only 24% of non-E. coli uropathogens, and evidence of polymicrobial infection has emerged. Price et al. used Expanded Quantitative Urine Culture (EQUC) to examine polymicrobial infections. 81% of the samples that detected E. coli also contained at least one additional pathogen.¹¹
• Vollstedt et al. utilized polymerase chain reaction (PCR). Out of 1,352 specimens that tested positive for bacteria, 56.1% were reported as being polymicrobial. While not all organisms within a sample are necessarily pathogenic, the possibility of a polymicrobial infection should be considered in symptomatic patients.²⁴
• When the limitations of SUC are removed, the opportunity for more informed decision making arises. The interactions between organisms present within an individual’s urobiome should be considered as they impact patient-reported outcomes.^7,12,25

Symptoms of a Persistent UTI

• Study participants with urinary urgency incontinence (UUI) have more urobiome diversity than non-UUI controls.^4,7 When lower urinary tract symptoms are present, consideration of a patient’s unique microbiota and microscopy examination can have a positive impact on treatment outcomes.
• A prospective, double-blind study performed by Warren et al. demonstrated that 48% of participants diagnosed with IC who underwent antibiotic treatment for 18 weeks reported either a reduction in urgency and pain, or an overall improvement in symptoms, compared to 24% of those in the placebo group. While further studies are needed, this outcome suggests that patients with urinary symptom complexes may have an undiagnosed UTI.^6,27

How Biofilm Contributes to Approximately 80% of Recurrent Infections

• Rate of recurrence: After the initial onset of an acute UTI, the risk of future recurrence increases. 19-24% of women will have a recurrent UTI within 6 months of their first infection, and for those patients who have a history of UTIs, 70% will have a recurrence  within one year.^10,29 Multiple factors previously discussed, such as standard urine culture (SUC) bias and sensitivity report limitations, contribute to increased recurrence rates. However, the presence of biofilm plays a significant role.
• Bacterial biofilms: Biofilms are bacterial communities encased in a polysaccharide matrix capable of adhering to and inside surfaces and tissues, expressing antibiotic resistance genes, and greatly influencing the development of chronic infections.²⁸ E. coli specifically is a high biofilm-producing bacterium, responsible for contributing to chronic and recurrent infection, with 62.5% of E. coli infections shown to produce biofilm.^6,30,31
• Prevalence: When compared with asymptomatic controls, 75% of patients with lower urinary tract symptoms (LUTS) had evidence of IBCs compared to 17% found in controls, indicating the potential role of biofilm in urinary symptoms.⁶ As explained by Scott et al., “IBCs may have a role not only in the etiology of recurrent UTI but also of chronic LUTS experienced by some women who are given the diagnosis of OAB or IC/BPS.”⁶
• Other biofilm-associated infections: Biofilms and IBCs are recognized as being associated with other tissue infections, such as dental infections, respiratory tract infections, endocarditis, prostatitis, and more.²⁸

References

1. Hilt EE, Mckinley K, Pearce MM, et al. Urine Is Not Sterile: Use of Enhanced Urine Culture Techniques To Detect Resident Bacterial Flora in the Adult Female Bladder. Journal of Clinical Microbiology. 2013;52(3):871-876. doi: 10.1128/jcm.02876-13 
2. Wolfe A, Toh E, Shibata N et al. Evidence of Uncultivated Bacteria in the Adult Female Bladder. J Clin Microbiol. 2012;50(4):1376-1383. doi: 10.1128/jcm.05852-11
3. Thomas-White K, Brady M, Wolfe AJ, Mueller ER. The Bladder Is Not Sterile: History and Current Discoveries on the Urinary Microbiome. Current Bladder Dysfunction Reports. 2016;11(1):18-24. doi: 10.1007/s11884-016-0345-8
4. Price T, Lin H, Gao X et al. Bladder bacterial diversity differs in continent and incontinent women: a cross-sectional study. Am J Obstet Gynecol. 2020;223(5):729.e1-729.e10. doi: 10.1016/j.ajog.2020.04.033
5. Thomas-White, K., Forster, S., Kumar, N., Van Kuiken, M., Putonti, C., Stares, M., Hilt, E., Price, T., Wolfe, A. and Lawley, T., 2018. Culturing of female bladder bacteria reveals an interconnected urogenital microbiota. Nature Communications, 9(1). doi: 10.1038/s41467-018-03968-5
6. Scott V, Haake D, Churchill B, Justice S, Kim J. Intracellular Bacterial Communities: A Potential Etiology for Chronic Lower Urinary Tract Symptoms. Urology. 2015;86(3):425-431. doi: 10.1016/j.urology.2015.04.002
7. Thomas-White K, Hilt E, Fok C et al. Incontinence medication response relates to the female urinary microbiota. Int Urogynecol J. 2015;27(5):723-733. doi: 10.1007/s00192-015-2847-x
8. Karstens L, Asquith M, Davin S et al. Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity? Front Cell Infect Microbiol. 2016;6. doi:10.3389/fcimb.2016.00078
9. Devillé, W., Yzermans, J., van Duijn, N., Bezemer, P., van der Windt, D. and Bouter, L., 2004. The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy. BMC Urology, 4(1). doi: 10.1186/1471-2490-4-4
10. Swamy S, Barcella W, Iorio MD, et al. Recalcitrant chronic bladder pain and recurrent cystitis but negative urinalysis: What should we do? International Urogynecology Journal. 2018;29(7):1035-1043. doi: 10.1007/s00192-018-3569-7
11. Price TK, Hilt EE, Dune TJ, Mueller ER, Wolfe AJ, Brubaker L. Urine trouble: should we think differently about UTI? International Urogynecology Journal. 2017;29(2):205-210. doi: 10.1007/s00192-017-3528-8
12. Price T, Dune T, Hilt E et al. The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms. J Clin Microbiol. 2016;54(5):1216-1222. doi: 10.1128/jcm.00044-16
13. Vollstedt A, Baunoch D, Wojno KJ, Luke N, Cline K, et al. (2020) Multisite Prospective Comparison of Multiplex Polymerase Chain Reaction Testing with Urine Culture for Diagnosis of Urinary Tract Infections in Symptomatic Patients. J Sur urology: JSU-102. doi: https://doi.org/10.1016/j.urology.2019.10.018
14. McDonald M, Kameh D, Johnson ME, Johansen TEB, Albala D, Mouraviev V. A Head-to-Head Comparative Phase II Study of Standard Urine Culture and Sensitivity Versus DNA Next-generation Sequencing Testing for Urinary Tract Infections. Rev Urol. 2017;19(4):213-220. doi: 10.3909/riu0780
15. Khasriya R, Sathiananthamoorthy S, Ismail S et al. Spectrum of Bacterial Colonization Associated with Urothelial Cells from Patients with Chronic Lower Urinary Tract Symptoms. J Clin Microbiol. 2013;51(7):2054-2062. doi: 10.1128/jcm.03314-12
16. Kumar A, Ellis P, Arabi Y et al. Initiation of Inappropriate Antimicrobial Therapy Results in a Fivefold Reduction of Survival in Human Septic Shock. Chest. 2009;136(5):1237-1248. doi: 10.1378/chest.09-0087
17. Bernard GR, Ely EW, Wright TJ, et al. Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis. Critical Care Medicine. 2001;29(11):2051-2059. doi: 10.1097/00003246-200111000-00003
18. Nannan Panday RS, Lammers EMJ, Alam N, Nanayakkara PWB. An overview of positive cultures and clinical outcomes in septic patients: a sub-analysis of the Prehospital Antibiotics Against Sepsis (PHANTASi) trial. Crit Care. 2019;23(1). doi: 10.1186/s13054-019-2431-8
19. Mulvey M. Induction and Evasion of Host Defenses by Type 1-Piliated Uropathogenic Escherichia coli. Science (1979). 1998;282(5393):1494-1497. doi:  10.1126/science.282.5393.1494
20. Price TK, Wolff B, Halverson T, et al. Temporal Dynamics of the Adult Female Lower Urinary Tract Microbiota. 2020. doi: 10.1101/2020.03.06.20032193 
21. Wojno KJ, Baunoch D, Luke N, et al. Multiplex PCR Based Urinary Tract Infection (UTI) Analysis Compared to Traditional Urine Culture in Identifying Significant Pathogens in Symptomatic Patients. Urology. 2020;136:119-126. doi: 10.1016/j.urology.2019.10.018
22. Gu W, Miller S, Chiu C. Clinical Metagenomic Next-Generation Sequencing for Pathogen Detection. Annual Review of Pathology: Mechanisms of Disease. 2019;14(1):319-338. doi: 10.1146/annurev-pathmechdis-012418-012751
23. Hilton SK, Castro-Nallar E, Pérez-Losada M, et al. Metataxonomic and Metagenomic Approaches vs. Culture-Based Techniques for Clinical Pathology. Frontiers in Microbiology. 2016;7. doi: 10.3389/fmicb.2016.00484
24. Vollstedt A, Baunoch D, Wolfe A, Luke N, Wojno KJ, et al. (2020) Bacterial Interactions as Detected by Pooled Antibiotic Susceptibility Testing (P-AST) in Polymicrobial Urine Specimens. J Sur urology: JSU-101. doi: 10.29011/JSU-101.100001
25. Thomas-White KJ, Gao X, Lin H, et al. Urinary microbes and postoperative urinary tract infection risk in urogynecologic surgical patients. International Urogynecology Journal. 2018;29(12):1797-1805. doi: 10.1007/s00192-018-3767-3
26. Barraud O, Ravry C, François B, Daix T, Ploy M-C, Vignon P. Shotgun metagenomics for microbiome and resistome detection in septic patients with urinary tract infection. International Journal of Antimicrobial Agents. 2019;54(6):803-808. doi: 10.1016/j.ijantimicag.2019.09.009
27. Warren JW, Horne LM, Hebel JR, Marvel RP, Keay SK, Chai TC. Pilot Study Of Sequential Oral Antibiotics For The Treatment Of Interstitial Cystitis. Journal of Urology. 2000;163(6):1685-1688. doi: 10.1016/s0022-5347(05)67520-9
28. Sharma D, Misba L, Khan A. Antibiotics versus biofilm: an emerging battleground in microbial communities. Antimicrobial Resistance & Infection Control. 2019;8(1). doi: 10.1186/s13756-019-0533-3
29. Brubaker L, Carberry C, Nardos R, Carter-Brooks C, Lowder J. American Urogynecologic Society Best-Practice Statement. Female Pelvic Med Reconstr Surg. 2018;24(5):321-335. doi: 10.1097/spv.0000000000000550
30. Anderson G, Palermo J, Schilling J, Roth R, Heuser J, Hultgren S. Intracellular Bacterial Biofilm-Like Pods in Urinary Tract Infections. Science (1979). 2003;301(5629):105-107. doi: 10.1126/science.1084550
31. Singh R, Sahore S, Kaur P, Rani A, Ray P. Penetration barrier contributes to bacterial biofilm-associated resistance against only select antibiotics, and exhibits genus-, strain- and antibiotic-specific differences. Pathogens and Disease. 2016;74(6). doi: 10.1093/femspd/ftw056
32. Katongole P, Nalubega F, Florence N, Asiimwe B, Andia I. Biofilm formation, antimicrobial susceptibility and virulence genes of Uropathogenic Escherichia coli isolated from clinical isolates in Uganda. BMC Infect Dis. 2020;20(1). doi: 10.1186/s12879-020-05186-1
33. Lerminiaux N, Cameron A. Horizontal transfer of antibiotic resistance genes in clinical environments. Can J Microbiol. 2019;65(1):34-44. doi: 10.1139/cjm-2018-0275