Введение. Структура инфекций нижних мочевыводящих путей имеет четко выраженные гендерные различия. Микробиота влагалища является ключевым фактором в патогенезе инфекций нижних мочевыводящих путей: аэробный вагинит предрасполагает к их инфицированию и повышает частоту развития цистита в 2,9 раза. Цель. Определить эффективность нифуратела как монотерапии у больных хроническим циститом с сопутствующим бактериальным вагинозом (БВ). Материалы и методы. Дизайн исследования: открытое несравнительное пилотное одноцентровое проспективное исследование, в которое вошли 23 пациентки, страдающие рецидивирующим циститом и БВ. Всем женщинам проведена монотерапия нифурателом (Макмирор производства Doppel Farmaceutici S.r.l., Италия) в таблетках по 200 мг трижды в день в течение 7 дней. Контрольные визиты осуществляли через 7, 90 и 180 дней. Результаты. БВ диагностирован у всех пациенток; у 19 (82,6%) женщин также обнаружен кандидоз влагалища. По окончании терапии у 17 (73,9%) пациенток отмечен отличный результат, у 4 (17,4%) – существенное улучшение, отсутствие эффекта – у 2 (8,7%). Через 3 мес после окончания терапии из 22 оставшихся в исследовании пациенток 18 (81,8%) жалоб на нарушение мочеиспускания и влагалищные выделения не предъявляли. Клинический анализ мочи у них в норме. Молекулярно-генетическое исследование биоценоза влагалища выявило умеренный дисбиоз; Candida spp. определялась только в 3 (13,6%) случаях. На 4-й визит явились 18 пациенток. В течение полугода после завершения монотерапии нифурателом пациентки не предъявляли жалоб. У всех восстановился нормоценоз влагалища с достаточным количеством Lactobacillus spp. Заключение. Монотерапия пациенток с рецидивирующим циститом и БВ высокоэффективна в отношении обоих заболеваний: у 73,9% женщин достигнуты стойкая нормализация анализов мочи и микробиоты влагалища, прекращение бактериурии. Двунаправленное действие нифуратела позволяет избежать полипрагмазии у данной категории пациенток.
Background. The structure of lower urinary tract infections has clear sex-based differences. The vaginal microbiota is a key factor in the pathogenesis of lower urinary tract infections: aerobic vaginitis predisposes to infection and increases the incidence of cystitis by 2.9 times. Aim. To determine the effectiveness of Nifuratel as monotherapy in patients with chronic cystitis and concomitant bacterial vaginosis (BV). Materials and methods. Study design: an open-label, non-comparative, pilot, single-center, prospective study, which included 23 patients with recurrent cystitis and BV. All women received monotherapy with Nifuratel (Macmiror manufactured by Doppel Farmaceutici S.r.l., Italy) in tablets of 200 mg 3 times a day for 7 days. Control visits were performed in 7.90 and 180 days. Results. BV was diagnosed in all patients; 19 (82.6%) women also had vaginal candidiasis. At the end of therapy, 17 (73.9%) patients showed an excellent outcome, 4 (17.4%) – a significant improvement, 2 (8.7%) – no effect. After the end of three-month therapy, 18 (81.8%) out of 22 patients who left in the study had no complaints of urinary disorders or vaginal discharge. Their urinalyses were normal. Molecular genetic analysis of the vaginal biocenosis showed moderate dysbiosis; Candida spp. was revealed only in 3 (13.6%) cases. 18 patients came for the 4th visit. Within six months after the end of monotherapy with Nifuratel, the patients had no complaints. They all achieved the recovery of vaginal normocenosis with a sufficient amount of Lactobacillus spp. Conclusion. Monotherapy in patients with recurrent cystitis and BV is highly effective for both diseases: 73.9% of women achieved stable normalization of urine and vaginal microbiota analyzes, removal of bacteriuria. The bi-directional action of Nifuratel allows to avoid polypharmacy in this category of patients.
1. Болезни мочевого пузыря. Под ред. Е.В.Кульчавеня, В.А.Краснова. Новосибирск: Наука, 2012.
[Diseases of the bladder. Ed. E.V.Kulchavenya, V.A.Krasnov. Novosibirsk: Nauka, 2012 (in Russian).]
2. Chan RC, Reid J, Irvin RT et al. Competitive exclusion of uropathogens from human uroepitelial cells by lactobacillus whole cells and cell wall fragments. Infect Immun 1985; 45: 84–9.
3. Wagenlehner F, Wullt B, Ballarini S et al. Social and economic burden of recurrent urinary tract infections and quality of life: a patient web-based study (GESPRIT). Expert Rev Pharmacoecon Outcomes Res 2018; 18 (1): 107–17. DOI: 10.1080/14737167.2017.1359543
4. Кульчавеня Е.В. Контроль внелегочного туберкулеза в Сибири и на Дальнем Востоке. Проблемы туберкулеза и болезней легких. 2008; 85 (9): 16–9.
[Kulchavenya EV. Extrapulmonary tuberculosis control in Siberia and the Far East. Problems of Tuberculosis and Lung Diseases. 2008; 85 (9): 16–9 (in Russian).]
5. Палагин И.С., Сухорукова М.В., Дехнич А.В. и др. и исследовательская группа «ДАРМИС-2018». Антибиотикорезистентность возбудителей внебольничных инфекций мочевых путей в России: результаты многоцентрового исследования «ДАРМИС-2018». КМАХ. 2019; 21 (2): 134–46. DOI: 10.36488/cmac.2019.2.134-146
[Palagin I.S., Sukhorukova M.V., Dehnich A.V. et al. and the DARMIS-2018 research group. Antibiotic resistance of causative agents of community-acquired urinary tract infections in Russia: results of a multicenter study "DARMIS-2018". KMAX. 2019; 21 (2): 134–46. DOI: 10.36488/cmac.2019.2.134-146 (in Russian).]
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[Malova I.O., Afanasyeva I.G. Bacterial vaginosis: is there an alternative to traditional drugs? Medical Advice. 2019; 7: 93–103 (in Russian).]
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[Kisina V.I. Bacterial vaginosis: a view of a dermatovenerologist. Clinical Dermatology and Venereology. 2016; 15 (2): 4–8 (in Russian).]
8. Polatti F. Bacterial Vaginosis, Atopobium Vaginae and Nifuratel. Curr Clin Pharmacol 2012; 7 (1): 36–40. DOI: 10.2174/157488412799218824
9. Stapleton AE. The Vaginal Microbiota and Urinary Tract Infection. Microbiol Spectr 2016; 4 (6): 10.1128/microbiolspec.UTI-0025-2016. DOI: 10.1128/microbiolspec.UTI-0025-2016
10. Harmanli OH, Cheng GY, Nyirjesy P et al. Urinary tract infections in women with bacterial vaginosis. Obstet Gynecol 2000; 95 (5): 710–2. DOI: 10.1016/s0029-7844 (99)00632-8
11. Lewis AL, Gilbert NM. Roles of the vagina and the vaginal microbiota in urinary tract infection: evidence from clinical correlations and experimental models. GMS Infect Dis 2020; 8: Doc02. DOI: 10.3205/id000046
12. Кульчавеня Е.В., Неймарк А.И., Борисенко Д.В., Капсаргин Ф.П. Острый неосложненный цистит: следуем ли мы рекомендациям? Урология. 2018; 6: 66–9. DOI: 10.18565/urology.2018.5.66-69
[Kulchavenya E.V., Neymark A.I., Borisenko D.V., Kapsargin F.P. Acute uncomplicated cystitis: are we following the recommendations? Urology. 2018; 6: 66–9. DOI: 10.18565/urology.2018.5.66-69 (in Russian).]
13. Wagenlehner F, Tandogdu Z, Bartoletti R et al. The Global Prevalence of Infections in Urology Study: A Long-Term,Worldwide Surveillance Study on Urological Infections. Pathogens. 2016; 5: 1–8. DOI: 10.3390/pathogens5010010
14. European Medicine Agency. https: //www.ema.europa.eu/en/news/fluoroquinolone-quinolone-antibiotics-prac-recommends-new-restrictions-use...
15. Naber KG, Cho YH, Matsumoto T, Sahaeffer AS. Immunoactive prophylaxis of urinary tract infections: a meta-analysis. Int J Antimicrobial Agents 2009; 33: 111–9.
16. Hamilton-Miller JM, Brumfitt W. Comparative in vitro activity of five nitrofurans. Chemotherapy 1978; 24 (3): 161–5. DOI: 10.1159/000237776
17. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 2005; 353: 1899–911.
18. Livengood CH. Bacterial vaginosis: an overview for 2009. Rev Obstet Gynecol 2009; 2: 28–37.
19. Togni G, Battini V, Bulgheroni A et al. In vitro activity of nifuratel on vaginal bacteria: could it be a good candidate for the treatment of bacterial vaginosis? Antimicrob Agents Chemother 2011; 55: 2490–2.
20. Иванова М.Д., Домбровский Я.А. Применение нифуратела в терапии инфекций мочевой системы у гинекологических больных. Почки. 2015; 1 (11): 68–71.
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21. Mendling W, Poli A, Magnani P. Clinical effects of nifuratel in vulvovaginal infections. A meta-analysis of metronidazole-controlled trials. Arzneimittelforschung 2002; 52 (10): 725–30. DOI: 10.1055/s-0031-1299958
22. Мордовец Е.М. Применение нифуратела в терапии инфекций мочевыводящих путей у пациентов детского и подросткового возраста. Почки. 2015; 2 (12): 52–5.
[Mordovets E.M. The use of nifuratel in the treatment of urinary tract infections in patients of childhood and adolescence. Kidneys. 2015; 2 (12): 52–5 (in Russian).]
________________________________________________
1. Diseases of the bladder. Ed. E.V.Kulchavenya, V.A.Krasnov. Novosibirsk: Nauka, 2012 (in Russian).
2. Chan RC, Reid J, Irvin RT et al. Competitive exclusion of uropathogens from human uroepitelial cells by lactobacillus whole cells and cell wall fragments. Infect Immun 1985; 45: 84–9.
3. Wagenlehner F, Wullt B, Ballarini S et al. Social and economic burden of recurrent urinary tract infections and quality of life: a patient web-based study (GESPRIT). Expert Rev Pharmacoecon Outcomes Res 2018; 18 (1): 107–17. DOI: 10.1080/14737167.2017.1359543
4. Kulchavenya EV. Extrapulmonary tuberculosis control in Siberia and the Far East. Problems of Tuberculosis and Lung Diseases. 2008; 85 (9): 16–9 (in Russian).
5. Palagin I.S., Sukhorukova M.V., Dehnich A.V. et al. and the DARMIS-2018 research group. Antibiotic resistance of causative agents of community-acquired urinary tract infections in Russia: results of a multicenter study "DARMIS-2018". KMAX. 2019; 21 (2): 134–46. DOI: 10.36488/cmac.2019.2.134-146 (in Russian).
6. Malova I.O., Afanasyeva I.G. Bacterial vaginosis: is there an alternative to traditional drugs? Medical Advice. 2019; 7: 93–103 (in Russian).
7. Kisina V.I. Bacterial vaginosis: a view of a dermatovenerologist. Clinical Dermatology and Venereology. 2016; 15 (2): 4–8 (in Russian).
8. Polatti F. Bacterial Vaginosis, Atopobium Vaginae and Nifuratel. Curr Clin Pharmacol 2012; 7 (1): 36–40. DOI: 10.2174/157488412799218824
9. Stapleton AE. The Vaginal Microbiota and Urinary Tract Infection. Microbiol Spectr 2016; 4 (6): 10.1128/microbiolspec.UTI-0025-2016. DOI: 10.1128/microbiolspec.UTI-0025-2016
10. Harmanli OH, Cheng GY, Nyirjesy P et al. Urinary tract infections in women with bacterial vaginosis. Obstet Gynecol 2000; 95 (5): 710–2. DOI: 10.1016/s0029-7844 (99)00632-8
11. Lewis AL, Gilbert NM. Roles of the vagina and the vaginal microbiota in urinary tract infection: evidence from clinical correlations and experimental models. GMS Infect Dis 2020; 8: Doc02. DOI: 10.3205/id000046
12. Kulchavenya E.V., Neymark A.I., Borisenko D.V., Kapsargin F.P. Acute uncomplicated cystitis: are we following the recommendations? Urology. 2018; 6: 66–9. DOI: 10.18565/urology.2018.5.66-69 (in Russian).
13. Wagenlehner F, Tandogdu Z, Bartoletti R et al. The Global Prevalence of Infections in Urology Study: A Long-Term,Worldwide Surveillance Study on Urological Infections. Pathogens. 2016; 5: 1–8. DOI: 10.3390/pathogens5010010
14. European Medicine Agency. https: //www.ema.europa.eu/en/news/fluoroquinolone-quinolone-antibiotics-prac-recommends-new-restrictions-use...
15. Naber KG, Cho YH, Matsumoto T, Sahaeffer AS. Immunoactive prophylaxis of urinary tract infections: a meta-analysis. Int J Antimicrobial Agents 2009; 33: 111–9.
16. Hamilton-Miller JM, Brumfitt W. Comparative in vitro activity of five nitrofurans. Chemotherapy 1978; 24 (3): 161–5. DOI: 10.1159/000237776
17. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 2005; 353: 1899–911.
18. Livengood CH. Bacterial vaginosis: an overview for 2009. Rev Obstet Gynecol 2009; 2: 28–37.
19. Togni G, Battini V, Bulgheroni A et al. In vitro activity of nifuratel on vaginal bacteria: could it be a good candidate for the treatment of bacterial vaginosis? Antimicrob Agents Chemother 2011; 55: 2490–2.
20. Ivanova M.D., Dombrovsky Y.A. The use of nifuratel in the treatment of urinary tract infections in gynecological patients. Kidneys. 2015; 1 (11): 68–71 (in Russian).
21. Mendling W, Poli A, Magnani P. Clinical effects of nifuratel in vulvovaginal infections. A meta-analysis of metronidazole-controlled trials. Arzneimittelforschung 2002; 52 (10): 725–30. DOI: 10.1055/s-0031-1299958
22. Mordovets E.M. The use of nifuratel in the treatment of urinary tract infections in patients of childhood and adolescence. Kidneys. 2015; 2 (12): 52–5 (in Russian).
Авторы
Е.В. Кульчавеня*1,2, А.А. Бреусов3
1 ФГБУ «Новосибирский научно-исследовательский институт туберкулеза» Минздрава России, Новосибирск, Россия;
2 ФГБОУ ВО «Новосибирский государственный медицинский университет» Минздрава России, Новосибирск, Россия;
3 Медицинский центр «Биовэр», Новосибирск, Россия
*urotub@yandex.ru
________________________________________________
Ekaterina V. Kulchavenya*1,2, Aleksandr A. Breusoff3
1 Novosibirsk Tuberculosis Research Institute, Novosibirsk, Russia;
2 Novosibirsk State Medical University, Novosibirsk, Russia;
3 Medical Center "Biover", Novosibirsk, Russia
*urotub@yandex.ru