RECURRENT URINARY TRACT INFECTIONS: CHALLENGES IN MANAGEMENT AND STRATEGIES FOR RECURRENCE PREVENTION - A REVIEW ARTICLE

Jakub Idziński; Anna Lubomska; Iga Kuba; Maria Janiszewska; Jakub Sapikowski; Agata Juchniewicz; Martyna Grześkowiak; Julita Jagodzińska; Igor Jętasiewicz

doi:10.31435/ijitss.4(48).2025.4449

Authors

Jakub Idziński Independent Public Multispecialist Healthcare Centre of the Ministry of Internal Affairs and Administration in Bydgoszcz, Bydgoszcz, Poland https://orcid.org/0009-0006-1058-9615
Anna Lubomska Independent Public Multispecialist Healthcare Centre of the Ministry of Internal Affairs and Administration in Bydgoszcz, Bydgoszcz, Poland https://orcid.org/0009-0003-7820-7669
Iga Kuba Pabianice Medical Centre, Pabianice, Poland https://orcid.org/0009-0001-5834-9075
Maria Janiszewska Dr Rafał Masztak Grochowski Hospital, Warsaw, Poland https://orcid.org/0009-0008-6704-8742
Jakub Sapikowski 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0008-7253-514X
Agata Juchniewicz 7th Naval Hospital in Gdańsk, Gdańsk, Poland https://orcid.org/0009-0009-4014-3413
Martyna Grześkowiak Florian Ceynowa Specialist Hospital in Wejherowo, Wejherowo, Poland https://orcid.org/0009-0003-8434-4870
Julita Jagodzińska Maria Skłodowska-Curie Provincial Specialist Hospital in Zgierz, Zgierz, Poland https://orcid.org/0009-0004-9403-9850
Igor Jętasiewicz Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland https://orcid.org/0009-0008-3351-6392

DOI:

https://doi.org/10.31435/ijitss.4(48).2025.4449

Keywords:

Urinary Tract Infection, Recurrent Urinary Tract Infection, UTI, Escherichia Coli, UPEC, Prevention, Prophylaxis, Antibiotic Resistance, Immunotherapy, D-Mannose

Abstract

Urinary tract infection (UTI) is one of the most common infectious diseases among adults and is caused by the presence of microorganisms in the urinary tract. Bacteria from the group of uropathogenic Escherichia coli strains, known as UPEC, play a central role in the etiology of these infections.

Epidemiological data indicate that nearly half of all women worldwide will experience at least one UTI in their lifetime, and a significant proportion will struggle with recurrent infections. This problem is particularly prevalent among young, sexually active women, as well as those of menopausal age, which may be partially explained by age-related impairments in immune function.

Currently, one of the major challenges in contemporary clinical practice is the increasing antibiotic resistance among UTI-causing bacteria. Specialists emphasize that targeted therapy, along with non-antibiotic or alternative methods, is essential in addressing this problem and preventing recurrent UTIs.

The following overview assesses the effectiveness of the most common methods of preventing recurrent urinary tract infections, based on recent publications. These approaches include both non-pharmacological methods such as adequate hydration, proper hygiene, and appropriate contraception, as well as pharmacological methods including antibiotic therapy, D-mannose supplementation, and vaginal estrogen therapy. Each method is based on a different mechanism of action, from mechanical removal of bacteria and competitive inhibition of bacterial adhesion to stimulation of immune defenses. Despite differing pathways, all these mechanisms share a single overarching goal: to prevent urinary tract infection.

References

Alghoraibi, H., Asidan, A., Aljawaied, R., Almukhayzim, R., Alsaydan, A., Alamer, E., Baharoon, W., Masuadi, E., Al Shukairi, A., Layqah, L., & Baharoon, S. (2023). Recurrent Urinary Tract Infection in Adult Patients, Risk Factors, and Efficacy of Low Dose Prophylactic Antibiotics Therapy. Journal of epidemiology and global health, 13(2), 200–211. https://doi.org/10.1007/s44197-023-00105-4

Juszczak, K., Dybowski, B., Holecki, M., Hryniewicz, W., Klimek, H., Kłoda, K., Sieroszewski, P., Drewa, T. (2024). Wytyczne Towarzystw Naukowych (PTU, PTGiP, PTMR) dotyczące diagnostyki, terapii i postępowania w pozaszpitalnych zakażeniach dolnych dróg moczowych. Przegląd Urologiczny, 142, 14-35.

Holecki, M., Duława, J. (2015). Rekomendacje diagnostyki, terapii i profilaktyki zakażeń układu moczowego u dorosłych..

Sihra, N., Goodman, A., Zakri, R., Sahai, A., & Malde, S. (2018). Nonantibiotic prevention and management of recurrent urinary tract infection. Nature reviews. Urology, 15(12), 750–776. https://doi.org/10.1038/s41585-018-0106-x

Zare, M., Vehreschild, M. J. G. T., & Wagenlehner, F. (2022). Management of uncomplicated recurrent urinary tract infections. BJU international, 129(6), 668–678. https://doi.org/10.1111/bju.15630

Jung, C., & Brubaker, L. (2019). The etiology and management of recurrent urinary tract infections in postmenopausal women. Climacteric : the journal of the International Menopause Society, 22(3), 242–249. https://doi.org/10.1080/13697137.2018.1551871

Anger, J., Lee, U., Ackerman, A. L., Chou, R., Chughtai, B., Clemens, J. Q., Hickling, D., Kapoor, A., Kenton, K. S., Kaufman, M. R., Rondanina, M. A., Stapleton, A., Stothers, L., & Chai, T. C. (2019). Recurrent Uncomplicated Urinary Tract Infections in Women: AUA/CUA/SUFU Guideline. The Journal of urology, 202(2), 282–289. https://doi.org/10.1097/JU.0000000000000296

Flores-Mireles, A. L., Walker, J. N., Caparon, M., & Hultgren, S. J. (2015). Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nature reviews. Microbiology, 13(5), 269–284. https://doi.org/10.1038/nrmicro3432

Sharma, A., Gupta, A., Meenakshi, ., Pandey, G., Awasthi, K., & Awasthi, A. (2025). Development of Tin Oxide Electrochemical Sensor for Sensitive Detection of Lactoferrin in Urinary Tract Infections. Journal of the Electrochemical Society, 172(8), 7

Khandelwal, P., Abraham, S. N., & Apodaca, G. (2009). Cell biology and physiology of the uroepithelium. American journal of physiology. Renal physiology, 297(6), F1477–F1501. https://doi.org/10.1152/ajprenal.00327.2009

Gupta, K., Stapleton, A. E., Hooton, T. M., Roberts, P. L., Fennell, C. L., & Stamm, W. E. (1998). Inverse association of H2O2-producing lactobacilli and vaginal Escherichia coli colonization in women with recurrent urinary tract infections. The Journal of infectious diseases, 178(2), 446–450. https://doi.org/10.1086/515635

Xie, J., Foxman, B., Zhang, L., & Marrs, C. F. (2006). Molecular epidemiologic identification of Escherichia coli genes that are potentially involved in movement of the organism from the intestinal tract to the vagina and bladder. Journal of clinical microbiology, 44(7), 2434–2441. https://doi.org/10.1128/JCM.00397-06

Coull, N., Mastoroudes, H., Popert, R., & O'Brien, T. S. (2008). Redefining urological history taking - anal intercourse as the cause of unexplained symptoms in heterosexuals. Annals of the Royal College of Surgeons of England, 90(5), 403–405. https://doi.org/10.1308/003588408X301000

Hooton, T. M., Scholes, D., Hughes, J. P., Winter, C., Roberts, P. L., Stapleton, A. E., Stergachis, A., & Stamm, W. E. (1996). A prospective study of risk factors for symptomatic urinary tract infection in young women. The New England journal of medicine, 335(7), 468–474. https://doi.org/10.1056/NEJM199608153350703

Huang, B., Fettweis, J. M., Brooks, J. P., Jefferson, K. K., & Buck, G. A. (2014). The changing landscape of the vaginal microbiome. Clinics in laboratory medicine, 34(4), 747–761. https://doi.org/10.1016/j.cll.2014.08.006

O'Hanlon, D. E., Moench, T. R., & Cone, R. A. (2013). Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PloS one, 8(11), e80074. https://doi.org/10.1371/journal.pone.0080074

Zárate, G., & Nader-Macias, M. E. (2006). Influence of probiotic vaginal lactobacilli on in vitro adhesion of urogenital pathogens to vaginal epithelial cells. Letters in applied microbiology, 43(2), 174–180. https://doi.org/10.1111/j.1472-765X.2006.01934.x

Stapleton A. E. (2016). The Vaginal Microbiota and Urinary Tract Infection. Microbiology spectrum, 4(6), 10.1128/microbiolspec.UTI-0025-2016. https://doi.org/10.1128/microbiolspec.UTI-0025-2016

Nygaard, I., & Linder, M. (1997). Thirst at work--an occupational hazard?. International urogynecology journal and pelvic floor dysfunction, 8(6), 340–343. https://doi.org/10.1007/BF02765593

Heinemann, C., & Reid, G. (2005). Vaginal microbial diversity among postmenopausal women with and without hormone replacement therapy. Canadian journal of microbiology, 51(9), 777–781. https://doi.org/10.1139/w05-070

Grin, P. M., Kowalewska, P. M., Alhazzan, W., & Fox-Robichaud, A. E. (2013). Lactobacillus for preventing recurrent urinary tract infections in women: meta-analysis. The Canadian journal of urology, 20(1), 6607–6614.

Gupta, K., Hillier, S. L., Hooton, T. M., Roberts, P. L., & Stamm, W. E. (2000). Effects of contraceptive method on the vaginal microbial flora: a prospective evaluation. The Journal of infectious diseases, 181(2), 595–601. https://doi.org/10.1086/315267

Handley, M. A., Reingold, A. L., Shiboski, S., & Padian, N. S. (2002). Incidence of acute urinary tract infection in young women and use of male condoms with and without nonoxynol-9 spermicides. Epidemiology (Cambridge, Mass.), 13(4), 431–436. https://doi.org/10.1097/00001648-200207000-00011

Jent, P., Berger, J., Kuhn, A., Trautner, B. W., Atkinson, A., & Marschall, J. (2022). Antibiotics for Preventing Recurrent Urinary Tract Infection: Systematic Review and Meta-analysis. Open forum infectious diseases, 9(7), ofac327. https://doi.org/10.1093/ofid/ofac327

Ahmed, H., Davies, F., Francis, N., Farewell, D., Butler, C., & Paranjothy, S. (2017). Long-term antibiotics for prevention of recurrent urinary tract infection in older adults: systematic review and meta-analysis of randomised trials. BMJ open, 7(5), e015233. https://doi.org/10.1136/bmjopen-2016-015233

Stapleton, A., Latham, R. H., Johnson, C., & Stamm, W. E. (1990). Postcoital antimicrobial prophylaxis for recurrent urinary tract infection. A randomized, double-blind, placebo-controlled trial. JAMA, 264(6), 703–706.

Lenger, S. M., Bradley, M. S., Thomas, D. A., Bertolet, M. H., Lowder, J. L., & Sutcliffe, S. (2020). D-mannose vs other agents for recurrent urinary tract infection prevention in adult women: a systematic review and meta-analysis. American journal of obstetrics and gynecology, 223(2), 265.e1–265.e13. https://doi.org/10.1016/j.ajog.2020.05.048

Mydock-McGrane, L. K., Cusumano, Z. T., & Janetka, J. W. (2016). Mannose-derived FimH antagonists: a promising anti-virulence therapeutic strategy for urinary tract infections and Crohn's disease. Expert opinion on therapeutic patents, 26(2), 175–197. https://doi.org/10.1517/13543776.2016.1131266

Srivastava, M., & Kapoor, V. P. (2005). Seed galactomannans: an overview. Chemistry & biodiversity, 2(3), 295–317. https://doi.org/10.1002/cbdv.200590013

Ganda, O. P., Soeldner, J. S., Gleason, R. E., Cleator, I. G., & Reynolds, C. (1979). Metabolic effects of glucose, mannose, galactose, and fructose in man. The Journal of clinical endocrinology and metabolism, 49(4), 616–622. https://doi.org/10.1210/jcem-49-4-616

Domenici, L., Monti, M., Bracchi, C., Giorgini, M., Colagiovanni, V., Muzii, L., & Benedetti Panici, P. (2016). D-mannose: a promising support for acute urinary tract infections in women. A pilot study. European review for medical and pharmacological sciences, 20(13), 2920–2925.

Kranjčec, B., Papeš, D., & Altarac, S. (2014). D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World journal of urology, 32(1), 79–84. https://doi.org/10.1007/s00345-013-1091-6

Williams, G., Hahn, D., Stephens, J. H., Craig, J. C., & Hodson, E. M. (2023). Cranberries for preventing urinary tract infections. The Cochrane database of systematic reviews, 4(4), CD001321. https://doi.org/10.1002/14651858.CD001321.pub6

González de Llano, D., Moreno-Arribas, M. V., & Bartolomé, B. (2020). Cranberry Polyphenols and Prevention against Urinary Tract Infections: Relevant Considerations. Molecules (Basel, Switzerland), 25(15), 3523. https://doi.org/10.3390/molecules25153523

Xia, J. Y., Yang, C., Xu, D. F., Xia, H., Yang, L. G., & Sun, G. J. (2021). Consumption of cranberry as adjuvant therapy for urinary tract infections in susceptible populations: A systematic review and meta-analysis with trial sequential analysis. PloS one, 16(9), e0256992. https://doi.org/10.1371/journal.pone.0256992

Lüthje, P., Hirschberg, A. L., & Brauner, A. (2014). Estrogenic action on innate defense mechanisms in the urinary tract. Maturitas, 77(1), 32–36. https://doi.org/10.1016/j.maturitas.2013.10.018

Tan-Kim, J., Shah, N. M., Do, D., & Menefee, S. A. (2023). Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women. American journal of obstetrics and gynecology, 229(2), 143.e1–143.e9. https://doi.org/10.1016/j.ajog.2023.05.002

Ferrante, K. L., Wasenda, E. J., Jung, C. E., Adams-Piper, E. R., & Lukacz, E. S. (2021). Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women: A Randomized Clinical Trial. Female pelvic medicine & reconstructive surgery, 27(2), 112–117. https://doi.org/10.1097/SPV.0000000000000749

Huber, M., Ayoub, M., Pfannes, S. D., Mittenbühler, K., Weis, K., Bessler, W. G., & Baier, W. (2000). Immunostimulatory activity of the bacterial extract OM-8. European journal of medical research, 5(3), 101–109.

Huber, M., Krauter, K., Winkelmann, G., Bauer, H. W., Rahlfs, V. W., Lauener, P. A., Blessmann, G. S., & Bessler, W. G. (2000). Immunostimulation by bacterial components: II. Efficacy studies and meta-analysis of the bacterial extract OM-89. International journal of immunopharmacology, 22(12), 1103–1111. https://doi.org/10.1016/s0192-0561(00)00070-9

Bauer, H. W., Alloussi, S., Egger, G., Blümlein, H. M., Cozma, G., Schulman, C. C., & Multicenter UTI Study Group (2005). A long-term, multicenter, double-blind study of an Escherichia coli extract (OM-89) in female patients with recurrent urinary tract infections. European urology, 47(4), 542–548. https://doi.org/10.1016/j.eururo.2004.12.009

Kim, K. S., Kim, J. Y., Jeong, I. G., Paick, J. S., Son, H., Lim, D. J., Shim, H. B., Park, W. H., Jung, H. C., & Choo, M. S. (2010). A prospective multi-center trial of Escherichia coli extract for the prophylactic treatment of patients with chronically recurrent cystitis. Journal of Korean medical science, 25(3), 435–439. https://doi.org/10.3346/jkms.2010.25.3.435

Brodie, A., El-Taji, O., Jour, I., Foley, C., & Hanbury, D. (2020). A Retrospective Study of Immunotherapy Treatment with Uro-Vaxom (OM-89®) for Prophylaxis of Recurrent Urinary Tract Infections. Current urology, 14(3), 130–134. https://doi.org/10.1159/000499248

Porto, B. C., Almeida, A. S., Terada, B. D., Gonçalves, F. G., Passerotti, C. C., Sardenberg, R. A., Otoch, J. P., & Cruz, J. A. (2025). Uro-vaxom (OM-89) for chronic UTI prevention: an updated meta-analysis, meta-regression and trial sequential analysis of recent clinical evidence. Minerva urology and nephrology, 77(5), 618–628. https://doi.org/10.23736/S2724-6051.25.06366-9

Das P. (2002). Vaginal vaccine for recurrent urinary-tract infections. The Lancet. Infectious diseases, 2(2), 68. https://doi.org/10.1016/s1473-3099(02)00200-1

Mak, Q., Greig, J., Dasgupta, P., Malde, S., & Raison, N. (2024). Bacterial Vaccines for the Management of Recurrent Urinary Tract Infections: A Systematic Review and Meta-analysis. European urology focus, 10(5), 761–769. https://doi.org/10.1016/j.euf.2024.04.002