References

medsovet

Медицинский Совет

Meditsinskiy sovet = Medical Council

2079-701X2658-5790

REMEDIUM GROUP Ltd.

10.21518/2079-701X-2022-16-14-164-170

medsovet-7034

Research Article

ГИНЕКОЛОГИЯ

GYNECOLOGY

Альтернативные виды терапии рецидивирующего цистита у женщин в менопаузе

Alternative therapies for recurrent cystitis in menopausal women

https://orcid.org/0000-0001-8062-7775

Кульчавеня

Е. В.

Kulchavenya

E. V.

Кульчавеня Екатерина Валерьевна, доктор медицинских наук, профессор, главный научный сотрудник, Новосибирский научно-исследовательский институт туберкулеза; профессор кафедры туберкулеза, Новосибирский государственный медицинский университет»; научный руководитель отдела урологии, Медицинский центр «Авиценна»

630040, Новосибирск, Охотская ул., д. 81, лит. А,

630091, Новосибирск, Красный проспект, д. 52,

630004, Новосибирск, проспект Дмитрова, д. 7

Ekaterina V. Kulchavenya, Dr. Sci. (Med.), Professor, Chief Researcher, Novosibirsk Tuberculosis Research Institute; Professor of the Department of Tuberculosis, Novosibirsk State Medical University; Scientific Director of the Department of Urology, Medical Center “Avicenna”

81, letter A, Okhotskaya St., Novosibirsk, 630040,

52, Krasny Ave., Novosibirsk, 630091,

7, Dmitrov Ave., Novosibirsk, 630004

urotub@yandex.ru

https://orcid.org/0000-0002-5435-2955

Трейвиш

Л. С.

Treyvish

L. S.

Трейвиш Любовь Степановна, врач акушер-гинеколог, заведующий гинекологическим отделением

630004, Новосибирск, проспект Дмитрова, д. 7

Lyubov S. Treyvish, Obstetrician-Gynecologist, Head of the Gynecological Department

7, Dmitrov Ave., Novosibirsk, 630004

ms.lubov_tr@mail.ru

Телина

Е. В.

Telina

E. V.

Телина Елена Владимировна, врач акушер-гинеколог, генеральный директор

630004, Новосибирск, проспект Дмитрова, д. 7

Elena V. Telina, Obstetrician-Gynecologist, General Director

7, Dmitrov Ave., Novosibirsk, 630004

urology-avicenna@mail.ru

Новосибирский научно-исследовательский институт туберкулеза; Новосибирский государственный медицинский университет; Медицинский центр «Авиценна»РоссияNovosibirsk Tuberculosis Research Institute; Novosibirsk State Medical University; Medical Center “Avicenna”Russian Federation

Медицинский центр «Авиценна»РоссияMedical Center “Avicenna”Russian Federation

2022

12082022

014164170

2022

Кульчавеня Е.В., Трейвиш Л.С., Телина Е.В.

Kulchavenya E.V., Treyvish L.S., Telina E.V.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.med-sovet.pro/jour/article/view/7034

Инфекции мочевыводящих путей (ИМП) регистрируются у 150–250 млн человек в год по всему миру. Ежегодные прямые и косвенные затраты на ИМП для всех пациентов оцениваются в размере от 2,4 до 3,5 млрд долл. США. Наиболее частой причиной ИМП является уропатогенная Escherichia coli, которая способна колонизировать уротелий, персистировать в эпителиальных клетках и образовывать покоящиеся биопленки. Этот бактериальный резервуар может быть как источником устойчивости бактерий, так и причиной рецидивов ИМП. Кроме того, рецидивирующие ИМП могут быть вызваны транслокацией других бактерий из желудочно-кишечного тракта или повторными инфекциями из внешних источников. Менопауза и беременность рассматриваются как осложняющие факторы ИМП. Среди немедикаментозных методов профилактики рецидивов ИМП у женщин в постменопаузе в руководстве Европейской ассоциации урологов упоминается пероральная вакцина OM-89 и D-манноза. Обоснование использования D-маннозы для профилактики ИМП основано на ее конкурентном ингибировании прикрепления бактерий к уротелиальным клеткам за счет связывания фимбрий 1-го типа, экспрессируемых на бактериях. Экзогенная D-манноза абсорбируется, но не метаболизируется организмом человека и выводится в неизмененном виде с мочой. Исследования in vivo и in vitro продемонстрировали способность маннозоподобных молекул уменьшать бактериальную нагрузку в мочевыводящих путях в 2 раза и более после 4 внутрипузырных инстилляций. Клинические исследования также продемонстрировали высокую эффективность шестимесячного перорального курса D-маннозы в профилактике ИМП.

Worldwide, urinary tract infections (UTIs) are reported in 150-250 million people per year. Annual direct and indirect costs of UTIs for overall patients are estimated to be from $2.4 billion to $3.5 billion Uropathogenic Escherichia coli is the most common cause of UTIs. These bacteria have the ability to colonize urothelium, persist in epithelial cells, and form quiescent biofilms. This bacterial reservoir may provide a source for bacterial persistence and UTIs recurrence. Besides, recurrent UTIs may be caused by the translocation of other bacteria which originate from the gastrointestinal tract or reinfections due to external sources. Menopause and pregnancy are considered as complicating factors that predispose to UTIs. Oral vaccine OM-89 and D-mannose are specified in the European Urological Association guidelines among non-pharmacological methods for the prevention of recurrent UTIs in postmenopausal women. The rationale to the use of D-mannose in UTI prophylaxis is based on its competitive inhibition of bacterial adherence to urothelial cells due to binding of type 1 fimbriae expressed on the bacteria. Exogenous D-mannose is absorbed, but not metabolized by the human body and it is excreted intact in urine. In vivo and in vitro studies showed the ability of mannose-like molecules to provide a 2-fold reduction of bacterial load in the urinary tract after 4 intravesical instillations. Clinical studies also demonstrated a high efficacy of the six months course of oral mannose in the prevention of UTIs.

менопаузаурогенитальный синдромциститхронический циститD-маннозаурогенитальные инфекции

menopauseurogenital syndromecystitischronic cystitisD-mannoseurogenital infections

References1

Кульчавеня Е.В., Жукова И.И. Внелегочный туберкулез – вопросов больше, чем ответов. Туберкулез и болезни легких. 2017;95(2):59–63. https://doi.org/10.21292/2075-1230-2017-95-2-59-63.

Kulchavenya E.V., Zhukova I.I. Extrapulmonary tuberculosis – more questions than answers. Tuberculosis and Lung Diseases. 2017;95(2):59–63. (In Russ.) https://doi.org/10.21292/2075-1230-2017-95-2-59-63.

Kulchavenya E., Kholtobin D., Shevchenko S. Challenges in urogenital tuberculosis. World J Urol. 2020;38(1):89–94. https://doi.org/10.1007/s00345-019-02767-x.

Hardy C.C., Keilich S.R., Harrison A.G., Knight B.E., Baker D.S., Smith P.P. The aging bladder phenotype is not the direct consequence of bladder aging. Neurourol Urodyn. 2019;38(8):2121–2129. https://doi.org/10.1002/nau.24149.

Hardy C.C., Al-Naggar I.M., Kuo C.-L., Kuchel G.A., Smith P.P. Aging changes in bladder hyperpolarization-activated cyclic nucleotide-gated channels are associated with increasing heterogeneity of adrenergic/mucosal influence on detrusor control in the mouse. J Gerontol A Biol Sci Med Sci. 2021;76(7):1153–1160. https://doi.org/10.1093/gerona/glab070.

Кульчавеня Е.В. Инфекции и секс: туберкулез и другие инфекции урогенитального тракта как причина сексуальных дисфункций. М.: ГЭОТАРМедиа; 2015. 168 с.

Kulchavenya E.V. Infections and sex: tuberculosis and other infections of the urogenital tract as a cause of sexual dysfunctions. Moscow: GEOTAR-Media; 2015. 168 p. (In Russ.)

Bonkat G., Bartoletti R., Bruyère F., Cai T., Geerlings S.E., Koves S. et al. EAU guidelines on urological infections. EAU Guidelines Office, Arnhem, the Netherlands; 2020. 65 p. Available at: https://docs.yandex.ru/docs/view?tm=1655975639&tld=ru&lanq=en&name=7._2020_EAU_10_2021.pdf&text=Bonkat%20G.%2C%20Bartoletti%20R.%2C%20Bruy%C3%A8re%20F.%2C%20Cai%20T.%2C%20Geerlings%20S.E.%2C%20Koves%20S.%20et%20al.%20EAU%20guidelines%20on%20urological%20infections.%202021&url=https%3A%2F%2Fanest.vn.ua%2Ffile%2F7._2020_EAU_10_2021.pdf&lr=213&mime=pdf&l10n=ru&sign=7102115bbd0c744755f27b4effd3d030&keyno=0&nosw=1&serpParams=tm%3D1655975639%26tld%3Dru%26lang%3Den%26name%3D7._2020_EAU_10_2021.pdf%26text%3DBonkat%2BG.%252C%2BBartoletti%2BR.%252C%2BBruy%25C3%25A8re%2BF.%252C%2BCai%2BT.%252C%2BGeerlings%2BS.E.%252C%2BKoves%2BS.%2Bet%2Bal.%2BEAU%2Bguidelines%2Bon%2Burological%2Binfections.%2B2021%26url%3Dhttps%253A%2F%2Fanest.vn.ua%2Ffile%2F7._2020_EAU_10_2021.pdf%26lr%3D213%26mime%3Dpdf%26l10n%3Dru%26sign%3D7102115bbd0c744755f27b4effd3d030%26keyno%3D0%26nosw%3D1.

Кульчавеня Е.В., Брижатюк Е.В., Хомяков В.Т., Бреусов А.А. Частота возникновения цистита в зависимости от вида контрацепции. Урология. 2013;(1):41–43. Режим доступа: https://lib.medvestnik.ru/articles/Chastota-vozniknoveniya-cistita-v-zavisimosti-ot-vida-kontracepcii.html.

Kulchavenya E.V., Brizhatyuk E.V., Khomyakov V.T., Breusov A.A. The incidence of cystitis, depending on the type of contraception. Urologiia. 2013;(1):41–43. (In Russ.) Available at: https://lib.medvestnik.ru/articles/Chastota-vozniknoveniya-cistita-v-zavisimosti-ot-vida-kontracepcii.html.

The 2020 genitourinary syndrome of menopause position statement of The North American Menopause Society. Menopause. 2020;27(9):976–992. https://doi.org/10.1097/GME.0000000000001609.

Panay N. Genitourinary syndrome of the menopause – dawn of a new era? Climacteric. 2015;18(Suppl_1):13–17. https://doi.org/10.3109/13697137.2015.1070564.

Kyriakides R., Jones P., Somani B.K. Role of D-Mannose in the prevention of recurrent urinary tract infections: evidence from a systematic review of the literature. Eur Urol Focus. 2021;7(5):1166–1169. https://doi.org/10.1016/j.euf.2020.09.004.

Scaglione F., Musazzi U.M., Minghetti P. Considerations on D-mannose mechanism of action and consequent classification of marketed healthcare products. Front Pharmacol. 2021;12:636377. https://doi.org/10.3389/fphar.2021.636377.

Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol. 2010;7(12):653–660. https://doi.org/10.1038/nrurol.2010.190.

Eells S.J., Bharadwa K., McKinnell J.A., Miller L.G. Recurrent urinary tract infections among women: comparative effectiveness of 5 prevention and management strategies using a Markov chain Monte Carlo model. Clin Infect Dis. 2014;58(2):147–160. https://doi.org/10.1093/cid/cit646.

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

Ciani O., Grassi D., Tarricone R. An economic perspective on urinary tract infection: the “costs of resignation”. Clin Drug Investig. 2013;33(4):255–261. https://doi.org/10.1007/s40261-013-0069-x.

Renard J., Ballarini S., Mascarenhas T., Zahran M., Quimper E., Choucair J., Iselin C.E. Recurrent lower urinary tract infections have a detrimental effect on patient quality of life: a prospective, observational study. Infect Dis Ther. 2014;4(1):125–135. https://doi.org/10.1007/s40121-014-0054-6.

Sarshar M., Behzadi P., Ambrosi C., Zagaglia C., Palamara A.T., Scribano D. FimH and anti-adhesive therapeutics: a disarming strategy against uropathogens. Antibiotics (Basel). 2020;9(7):397. https://doi.org/10.3390/antibiotics9070397.

Berry R.E., Klumpp D.J., Schaeffer A.J. Urothelial cultures support intracellular bacterial community formation by uropathogenic Escherichia coli. Infect Immun. 2009;77(7):2762–2772. https://doi.org/10.1128/IAI.00323-09.

Симаненков В.И., Маев И.В., Ткачева О.Н., Алексеенко С.А., Андреев Д.Н., Бордин Д.С. и др. Синдром повышенной эпителиальной проницаемости в клинической практике. мультидисциплинарный национальный консенсус. Кардиоваскулярная терапия и профилактика. 2021;20(1):2758. https://doi.org/10.15829/1728-8800-2021-2758.

Simanenkov V.I., Maev I.V., Tkacheva O.N., Alekseenko S.A., Andreev D.N., Bordin D.S. et al. Syndrome of increased epithelial permeability in clinical practice. Multidisciplinary national Consensus. Cardiovascular Therapy and Prevention (Russian Federation). 2021;20(1):2758. (In Russ.) https://doi.org/10.15829/1728-8800-2021-2758.

Thänert R., Reske K.A., Hink T., Wallace M.A., Wang B., Schwartz D.J. et al. Comparative genomics of antibiotic-resistant uropathogens implicates three routes for recurrence of urinary tract infections. Am Soc Microbiol. 2019;10(4):e01977–e019819. https://doi.org/10.1128/mBio.01977-19.

Loubet P., Ranfaing J., Dinh A., Dunyach-Remy C., Bernard L., Bruyère F. et al. Alternative therapeutic options to antibiotics for the treatment of urinary tract infections. Front Microbiol. 2020;11:1509. https://doi.org/10.3389/fmicb.2020.01509.

Hu X., Shi Y., Zhang P., Miao M., Zhang T., Jiang B. D-Mannose: properties, production, and applications: An overview. Compr Rev Food Sci Food Saf. 2016;15(4):773–785. https://doi.org/10.1111/1541-4337.12211.

Zhang D., Chia C., Jiao X., Jin W., Kasagi S., Wu R. et al. D-mannose induces regulatory T cells and suppresses immunopathology. Nat Med. 2017;23(9):1036–1045. https://doi.org/10.1038/nm.4375.

Alton G., Hasilik M., Niehues R., Panneerselvam K., Etchison J.R., Fana F., Freeze H.H. Direct utilization of mannose for mammalian glycoprotein biosynthesis. Glycobiology. 1998;8(3):285–295. https://doi.org/10.1093/glycob/8.3.285.

Wellens A., Garofalo C., Nguyen H., Van Gerven N., Slättegård R., Hernalsteens J.-P. et al. Intervening with urinary tract infections using anti-adhesives based on the crystal structure of the FimH-oligomannose-3 complex. PLoS ONE. 2008;3(4):e2040. https://doi.org/10.1371/journal.pone.0002040.

Alton G., Kjaergaard S., Etchison J.R., Skovby F., Freeze H.H. Oral ingestion of mannose elevates blood mannose levels: a first step toward a potential therapy for carbohydrate-deficient glycoprotein syndrome type I. Biochem Mol Med. 1997;60(2):127–133. https://doi.org/10.1006/bmme.1997.2574.

Durán J.M., Cano M., Peral M.J., Ilundáin A.A. D-mannose transport and metabolism in isolated enterocytes. Glycobiology. 2004;14(6):495–500. https://doi.org/10.1093/glycob/cwh059.

Sharma V., Ichikawa M., Freeze H.H. Mannose metabolism: more than meets the eye. Biochem Biophys Res Commun. 2014;453(2):220–228. https://doi.org/10.1016/j.bbrc.2014.06.021.

Wei Z., Huang L., Cui L., Zhu X. Mannose: Good player and assister in pharmacotherapy. Biomed Pharmacother. 2020;129:110420. https://doi.org/10.1016/j.biopha.2020.110420.

Sharon N. Carboydrates as future anti-adhesion drugs for infectious diseases. Biochim Biophys Acta. 2006;1760(4):527–537. https://doi.org/10.1016/j.bbagen.2005.12.008.

Schaeffer A.J., Amundsen S.K., Jones J.M. Effect of carbohydrates on adherence of Escherichica coli to human urinary tract epithelial cells. Infect Immun. 1980;30(2):531–537. https://doi.org/10.1128/iai.30.2.531-537.1980.

Altarac S., Papeš D. Use of D-mannose in prophylaxis of recurrent urinary tract infections (UTIs) in women. BJU Int. 2014;113(1):9–10. https://doi.org/10.1111/bju.12492.

Zhou G., Mo W.J., Sebbel P., Min G., Neubert T.A., Glockshuber R. et al. Uroplakin Ia is the urothelial receptor for uropathogenic escherichia coli: evidence from in vitro fimh binding. J Cell Sci. 2001;114(Pt_22):4095–4103. https://doi.org/10.1242/jcs.114.22.4095.

Cusumano C.K., Pinkner J.S., Han Z., Greene S.E., Ford B.A., Crowley J.R. et al. Treatment and prevention of urinary tract infection with orally active FimH inhibitors. Sci Transl Med. 2011;3(109):109ra115. https://doi.org/10.1126/scitranslmed.3003021.

Aydin A., Ahmed K., Zaman I., Khan M.S., Dasgupta P. Recurrent urinary tract infections in women. Int Urogynecol J. 2015;26(6):795–804. https://doi.org/10.1007/s00192-014-2569-5.

Kalas V., Pinkner J.S., Hannan T.J., Hibbing M.E., Dodson K.W. et al. Evolutionary fine-tuning of conformational ensembles in FimH during host-pathogen interactions. Sci Adv. 2017;3(2):e1601944. https://doi.org/10.1126/sciadv.1601944.

Sauer M.M., Jakob R.P., Luber T., Canonica F., Navarra G., Ernst B. et al. Binding of the bacterial adhesin fimh to its natural, multivalent high-mannose type glycan targets. J Am Chem Soc. 2019;141(2):936–944. https://doi.org/10.1021/jacs.8b10736.

Pan Y.T., Xu B., Rice K., Smith S., Jackson R., Elbein A.D. Specificity of the high-mannose recognition site between Enterobacter cloacae pili adhesin and HT-29 cell membranes. Infect Immun. 1997;65(10):4199–4206. https://doi.org/10.1128/iai.65.10.4199-4206.1997.

Jones C.H., Pinkner J.S., Roth R., Heuser J., Nicholes A.V., Abraham S.N., Hultgren S.J. FimH adhesin of type 1 pili is assembled into a fibrillar tip structure in the Enterobacteriaceae. Proc Natl Acad Sci U S A. 1995;92(6):2081–2085. https://doi.org/10.1073/pnas.92.6.2081.

Poole N.M., Green S.I., Rajan A., Vela L.E., Zeng X.-L., Estes M.K., Maresso A.W. Role for FimH in extraintestinal pathogenic escherichia coli invasion and translocation through the intestinal epithelium. Infect Immun. 2017;85(11):e00581–e00587. https://doi.org/10.1128/IAI.00581-17.

Mydock-McGrane L.K., Hannan T.J., Janetka J.W. Rational design strategies for FimH antagonists: new drugs on the horizon for urinary tract infection and Crohn’s disease. Expert Opin Drug Discov. 2017;12(7):711–731. https://doi.org/10.1080/17460441.2017.1331216.

Ohman L., Magnusson K.E., Stendahl O. Effect of monosaccharides and ethyleneglycol on the interaction between Escherichia coli bacteria and Octyl-Sepharose. Acta Pathol Microbiol Immunol Scand B. 1985;93(2): 133–138. https://doi.org/10.1111/j.1699-0463.1985.tb02864.x.

Feenstra T., Thøgersen M.S., Wieser E., Peschel A., Ball M.J., Brandes R. et al. Adhesion of Escherichia coli under flow conditions reveals potential novel effects of FimH mutations. Eur J Clin Microbiol Infect Dis. 2017;36(3):467–478. https://doi.org/10.1007/s10096-016-2820-8.

Ofek I., Goldhar J., Eshdat Y., Sharon N. The importance of mannose specific adhesins (lectins) in infections caused by Escherichia coli. Scand J Infect Dis Suppl. 1982;33:61–67. Available at: https://pubmed.ncbi.nlm.nih.gov/6753135/.

Schwartz D.J., Kalas V., Pinkner J.S., Chen S.L., Spaulding C.N., Dodson K.W., Hultgren S.J. Positively selected FimH residues enhance virulence during urinary tract infection by altering FimH conformation. Proc Natl Acad Sci U S A. 2013;110(39):15530–15537. https://doi.org/10.1073/pnas.1315203110.

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

Del Popolo G., Nelli F. Recurrent bacterial symptomatic cystitis: A pilot study on a new natural option for treatment. Arch Ital Urol Androl. 2018;90(2):101–103. https://doi.org/10.4081/aiua.2018.2.101.

Pugliese D., Acampora A., Porreca A., Schips L., Cindolo L. Effectiveness of a novel oral combination of D-Mannose, pomegranate extract, prebiotics and probiotics in the treatment of acute cystitis in women. Arch Ital Urol Androl. 2020;92(1):34–38. https://doi.org/10.4081/aiua.2020.1.34.

Phé V., Pakzad M., Haslam C., Gonzales G., Curtis C., Porter B. et al. Open label feasibility study evaluating D-mannose combined with home-based monitoring of suspected urinary tract infections in patients with multiple sclerosis. Neurourol Urodyn. 2017;36(7):1770–1775. https://doi.org/10.1002/nau.23173.

Parrino B., Schillaci D., Carnevale I., Giovannetti E., Diana P., Cirrincione G., Cascioferro S. Synthetic small molecules as anti-biofilm agents in the struggle against antibiotic resistance. Eur J Med Chem. 2019;161:154–178. https://doi.org/10.1016/j.ejmech.2018.10.036.

Mainini G., Passaro M., Schiattarella A., Franciscis P., Donna M.C.D., Trezza G. Prevention and treatment of cystitis during menopause: efficacy of a nutraceutical containing D-mannose, inulin, cranberry, bearberry, Olea europaea, Orthosiphon and Lactobacillus acidophilus. Prz Menopauzalny. 2020;19(3):130–134. https://doi.org/10.5114/pm.2020.99567.

Domenici L., Monti M., Bracchi C., Giorgini M., Colagiovanni V., Muzii L., Panici P.B. D-mannose: a promising support for acute urinary tract infections in women. A pilot study. Eur Rev Med Pharmacol Sci. 2016;20(13):2920–2925. Available at: https://pubmed.ncbi.nlm.nih.gov/27424995/.

Alton G., Hasilik M., Niehues R., Panneerselvam K., Etchison J.R., Fana F., Freeze H.H. Direct manipulation of mannose for mammalian glycoprotein biosynthesis. Glycobiology. 2001;8(3):285–295. https://doi.org/10.1093/glycob/8.3.285.

Davis J.A., Freeze H.H. Studies of mannose metabolism and effects of long-term mannose ingestion in the mouse. Biochim Biophys Acta. 2001; 1528(2–3):116–126. https://doi.org/10.1016/s0304-4165(01)00183-0.

Bouckaert J., Berglund J., Schembri M., De Genst E., Cools L., Wuhrer M. et al. Receptor binding studies disclose a novel class of high-affinity inhibitors of the Escherichia coli FimH adhesin. Mol Microbiol. 2005;55(2):441–455. https://doi.org/10.1111/j.1365-2958.2004.04415.x.

Lopez A.I., Kumar A., Planas M.R., Li Y., Nguyen T.V., Cai C. Biofunctionalization of silicone polymers using poly (amidoamine) dendrimers and a mannose derivative for prolonged interference against pathogen colonization. Bimaterials. 2011;32(19):4336–4346. https://doi.org/10.1016/j.biomaterials.2011.02.056.

Franssen M., Cook J., Robinson J., Williams N., Glogowska M., Yang Y. et al. D-MannosE to prevent Recurrent urinary tract InfecTions (MERIT): protocol for a randomised controlled trial. BMJ Open. 2021;11(1):e037128. https://doi.org/10.1136/bmjopen-2020-037128.

Кузьменко А.В., Кузьменко В.В., Гяургиев Т.А. Эффективность комбинированной антибактериально-пребиотической терапии в сочетании с D-маннозой у женщин с неосложненной инфекцией нижних мочевых путей. Урология. 2019;(6):38–43. https://doi.org/10.18565/urology.2019.6.38-43.

Kuzmenko A.V., Kuzmenko V.V., Gyaurgiev T.A. Efficacy of combined antibacterial-prebiotic therapy in combination with D-mannose in women with uncomplicated lower urinary tract infection. Urologiia. 2019;(6):38–43. (In Russ.) https://doi.org/10.18565/urology.2019.6.38-43.

Кузьмин И.В., Слесаревская М.Н., Аль-Шукри С.Х. Антиадгезивная стратегия неантибактериальной профилатики рецидивирующей инфекции нижних мочевыводящих путей. Урология. 2021;(3):5–12. https://doi.org/10.18565/urology.2021.3:5-12.

Kuzmin I.V., Slesarevskaya M.N., Al-Shukri S.Kh. Antiadhesive strategy for non-antibacterial prophylaxis of recurrent lower urinary tract infections. Urologiia. 2021;(3):5–12. (In Russ.) https://doi.org/10.18565/urology.2021.3:5-12.

Тетерина Т.А., Ищук М.П., Аполихина И.А. Современные подходы к терапии и профилактике рецидивирующих циститов у беременных с применением D-маннозы: результаты проспективного рандомизированного клинического исследования. Эффективная фармакотерапия. 2021;17(9):6–14. Режим доступа: https://umedp.ru/articles/sovremennye_podkhody_k_terapii_i_profilaktike_retsidiviruyushchikh_tsistitov_u_beremennykh_s_primene.html.

Teterina T.A., Ishchuk M.P., Apolikhina I.A. Modern approaches to the recurrent cystitis treatment and prevention in pregnant women using d-mannose: results of a prospective randomized clinical trial. Effective Pharmacotherapy. 2021;17(9):6–14. (In Russ.) Available at: https://umedp.ru/articles/sovremennye_podkhody_k_terapii_i_profilaktike_retsidiviruyushchikh_tsistitov_u_beremennykh_s_primene.html.

The authors declare that there are no conflicts of interest present.