Systematic review of the efficacy and safety of nifuratel for women with diseases accompanied by pathological discharge from the genital tract

DOI

https://dx.doi.org/10.18565/aig.2023.248

Apolikhina I.A., Rakhmatulina М.R., Priputnevich Т.V., Gorbunova Е.А., Guschin А.Е., Potekaev N.N., Baranov I.I.
1) Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia; 2) State Scientific Center for Dermatovenereology and Cosmetology, Ministry of Health of Russia, Moscow, Russia; 3) Moscow Scientific and Practical Center for Dermatovenereology and Cosmetology, Moscow Healthcare Department, Moscow, Russia

Objective: To evaluate the clinical and laboratory efficacy and safety of nifuratel for women with diseases accompanied by pathological discharge from the genital tract.
Materials and methods: This systematic review was conducted according to the PRISMA checklist. The analysis included controlled clinical studies for the period 1972–2023 which evaluated the efficacy and safety of oral and/or vaginal administration of nifuratel in women over the age of 18 with bacterial vaginosis, aerobic vaginitis, candidiasis vulvovaginitis, mixed vaginitis and trichomoniasis.
Results: After selecting the proper publications and excluding duplicates, the qualitative analysis included 14 studies (5 randomized and 9 non-randomized); totally, there were 3,337 patients including 544 pregnant women. The quantitative synthesis and meta-analysis included 9 clinical studies. According to received data, a statistically significant difference in clinical and microbiological efficacy was determined in favor of nifuratel in comparison with other drugs (odds ratio (OR)=1.03, 95% CI [1.00, 1.07], p=0.03 and OR=1.15, 95% CI [1.04, 1.27], p=0.005, respectively). There was a statistically significant difference in the frequency of relapses after a course of therapy in favor of nifuratel in comparison with other drugs (OR=0.36, 95% CI [0.19, 0.68], p=0.001). None of the included studies showed any serious side effects after the treatment with the drug.
Conclusion: The use of nifuratel both as monotherapy and in combination with nystatin surpasses other drugs in clinical and microbiological efficacy in the treatment of diseases accompanied by pathological discharge from the genital tract in women; it also shows a lower frequency of relapses. Nevertheless, additional well-planned studies with standardized criteria for evaluating results and long-term follow-up periods can allow the women with vaginitis and bacterial vaginosis to make a better choice among antimicrobial therapy options.

Authors’ contributions: Apolikhina I.A., Gorbunova E.A. – developing the concept and design of the study, search and analysis of the literature, writing the text, approving the final version of the article; Rakhmatulina M.R., Priputnevich T.V., Guschin A.E., Potekaev N.N., Baranov I.I. – text editing, approval of the final version of the article.
Conflicts of interes: Authors declare lack of the possible conflicts of interests.
Funding: The study was conducted without sponsorship.
For citation: Apolikhina I.A., Rakhmatulina М.R., Priputnevich Т.V., Gorbunova Е.А., Guschin А.Е., Potekaev N.N., Baranov I.I. Systematic review of the efficacy and safety of nifuratel for women with diseases accompanied by pathological discharge from the genital tract. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (11): 48-58 (in Russian)
https://dx.doi.org/10.18565/aig.2023.248

nifuratel

vaginal infections

bacterial vaginosis

aerobic vaginitis

infectious vaginitis

candidiasis vulvovaginitis

recurrent vulvovaginitis

pregnancy

pathological discharge

Full text (in Russian)

Machado D., Castro J., Palmeira-de-Oliveira A., Martinez-de-Oliveira J., Cerca N. Bacterial vaginosis biofilms: challenges to current therapies and emerging solutions. Front. Microbiol. 2016; 6: 1528. https://dx.doi.org/10.3389/fmicb.2015.01528.
Carr P.L., Felsenstein D., Friedman R.H. Evaluation and management of vaginitis. J. Gen. Intern. Med., 1998; 13(5): 335-46. https://dx.doi.org/10.1046/j.1525-1497.1998.00101.x.
Sobel J.D., Ferris D., Schwebke J., Nyirjesy P., Wiesenfeld H.C., Peipert J. et al. Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis. Am. J. Obstet. Gynecol. 2006; 194(5): 1283-9. https://dx.doi.org/10.1016/j.ajog.2005.11.041.
Dubini F., Furneri P. Attività antimicrobica del nifuratel [Antimicrobial activity of nifuratel]. G. Ital. Chemioter. 1985; 32(3): 545-52. Italian.
Mendling W., Mailland F. Microbiological and pharm-acotoxicological profile of nifuratel and its favourable risk/benefit ratio for the treatment of vulvo-vaginal infections. Arzneimittelforschung. 2002; 52(1):8-13. https://dx.doi.org/10.1055/s-0031-1299849.
Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;29:372:n71. https://dx.doi.org/10.1136/bmj.n71.
Higgins J.P.T., Thomas J., Chandler J., Cumpston M., Li T., Page M.J., Welch V.A., eds. Cochrane handbook for systematic reviews of interventions version 6.1. Updated September 2020. Available at: www.training.cochrane.org/handbook
Sterne J.A.C., Savović J., Page M.J., Elbers R.G., Blencowe N.S., Boutron I. et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019; 366: l4898. https://dx.doi.org/10.1136/bmj.l4898.
Sterne J.A.C., Hernán M.A., Reeves B.C., Savović J., Berkman N.D., Viswanathan M. et al. ROBINS-I: a tool for assessing risk of bias in non- randomized studies of interventions. BMJ. 2016; 355: i4919. https://dx.doi. org/10.1136/bmj.i4919.
National Heart, Lung and Blood Institute. Study Quality Assessment Tools. https://www.nhlbi.nih.gov/health-topics/study-quality- assessment-tools De La Hoz F.J.E. Efficacy and safety of nifuratel-nystatin in the treatment of mixed vaginitis, in pregnant women from quindío, 2013-2017. Randomized clinical trial. Pregn. Womens Health Care Int. J. 2022; 2(1): 1-7. https://dx.doi.org/10.53902/PWHCIJ.2022.02.000508.
De La Hoz F.J.E. Efficacy and safety of the combination nifuratel-nystatin and clindamycin-clotrimazole, in the treatment of bacterial vaginosis. Randomized controlled clinical trial. Int. J. Reprod. Med. Sex Health. 2021; 3: 1-10. https://dx.doi.org/10.36811/ijrmsh.2021.110010.
Обоскалова Т.А., Кононова И.Н., Ворошилина Е.С., Тагинцева М.Л. Особенности современного течения инфекционных процессов половых путей у женщин и пути их коррекций. Эффективная фармакотерапия. Акушерство и гинекология. 2012; 5: 6-10. [Oboskalova T.A., Kononova I.N., Voroshilina E.S., Tagintseva M.L. Characteristics of modern infectious processes of urogenital tract in women and the ways of their corrections. Effective pharmacotherapy. Obstetrics and gynecology. 2012; 5: 6-10 (in Russian)].
Перламутров Ю.Н., Гомберг М.А., Чернова Н.И., Бочкова О.И., Щербо С.Н. Сравнительная эффективность нифуратела и метронидазола в терапии бактериального вагиноза, ассоциированного с Atopobium vaginae. Вопросы гинекологии, акушерства и перинатологии. 2011;10(3): 22-5. [Perlamutrov Yu.N., Gomberg M.A., Chernova N.I., Bochkova O.I., Shcherbo S.N. A comparative effectiveness of nifuratel and metronidazole in therapy of bacterial vaginosis associated with Atopobium vaginae. Gynecology, Obstetrics and Perinatology. 2011; 10(3): 22-5. (in Russian)].
Серов В.Н., Шаповаленко С.А. Микробиоценоз влагалища и инфекционные вульвовагиниты: выбор препарата для рациональной терапии. Вопросы гинекологии, акушерства и перинатологии. 2004; 3(4): 27-31. [Serov V.N., Shapovalenko S.A. Vaginal microbiocenosis and infectious vulvovaginitis: choice of drug for rational therapy. Gynecology, Obstetrics and Perinatology. 2004; 3(4): 27-31. (in Russian)].
Mendling W., Caserini M., Palmieri R. O02.1 A randomised, controlled study to assess the efficacy and safety of nifuratel vaginal tablets on bacterial vaginosis. Sexually Transmitted Infections. 2013; 89(Suppl 1): A28. https://dx.doi.org/10.1136/sextrans-2013-051184.0089.
Wang H., Han X.-X., Lang G.-Q. Efficacy and safety of Honghefujie lotion plus Nifuratel nysfungin vaginal soft capsules for Candida vaginitis in pregnant women. Evaluation and Analysis of Drug-Use in hospitals of China. 2015; 3:306-8.
Ruochun T., Qingcha L. The study of nifuratel-nystatin vaginal suppositories used in pregnant women with vulvovaginal candidiasis. Guang. Med. J. 2008; 04: 56-7.
Wang R., Zhang C. Efficacy and safety of combination of nifuratel tablets with Baofukang suppository on treatment and recurrence of vaginitis in pregnancy. Trop. J. Pharmac. Res. 2021; 20(6): 1267-72. https://dx.doi.org/10.4314/tjpr.v20i6.24.
Кононова И.Н., Доброхотова Ю.Э., Карева Е.Н., Семиошина О.Е., Шмакова Н.А. Вульвовагиниты и их коррекция у пациенток с цервикальными ВПЧ-ассоциированными заболеваниями в свете учения о патоморфозе. Гинекология. 2021; 23 (2): 177-83. [Kononova I.N., Dobrokhotova Yu.E., Kareva E.N., Semioshina O.E., Shmakova N.A. Vulvovaginitis and their correction in patients with cervical HPV-associated diseases in the light of the doctrine of pathomorphosis. Gynecology. 2021; 23(2): 177-83. (in Russian)]. https://dx.doi.org/10.26442/20795696.2021.2.200844.
Baron A. Treatment of trichomonadosis by means of metronidazole and nifuratel administered orally compared to simultaneous administration per os and per vagina. Wiad Parazytol. 1973;19(3):511-4.
Block E. Effects of nifuratel and metronidazole in the treatment of trichomonas. Lakartidningen. 1972; 69(45):5210-2.
Goisis M., Oppo G.T. Treatment of female trichomoniasis. In: F. Gasparri, G. Gargani, P. Periti (eds.). Diagnosis and chemiotheraphy of urogenital infections. Edizioni Mediche P. Periti, Firenze. 1972: 197-202.
Pathak U.N., Sur S.K., Farrand R.J. Comparison of metronidazole/nystatin and nifuratel in the treatment of vaginitis. Br. J. Clin. Pract. 1975; 29(10): 270-2.
Перепанова Т.С. Нитрофураны в урологической практике: все ли они одинаковые. Экспериментальная и клиническая урология. 2018; 3: 91-100. [Perepanova T.S. Nitrofurans in urological practice: are they all the same. Experimental and Clinical Urology. 2018; 3: 91-100. (in Russian)]
Mendling W., Poli A., Magnani P. Clinical effects of nifuratel in vulvovaginal infections. a meta-analysis of metronidazole-controlled trials. Arzneimittel-Forschung. 2002; 52(10): 725-30. https://dx.doi.org/10.1055/s-0031-1299958.
Аполихина И.А., Гущин А.Е., Эфендиева З.Н., Тюленев Ю.А. Возможности антимикробной терапии заболеваний, сопровождающихся патологическими выделениями из половых путей: результаты многоцентровой наблюдательной программы «Проспект». Акушерство и гинекология. 2021; 12: 167-76. [Apolikhina I.A., Guschin A.E., Efendieva Z.N., Tyulenev Yu.A. Opportunities for antimicrobial therapy of diseases accompanied by pathological discharge from the genital tract: results of the multicenter observational Prospectus program. Obstetrics and Gynecology. 2021; (12): 167-76 (in Russian)]. https://dx.doi.org/10.18565/aig.2021.12.167-176.
Togni G., Battini V., Bulgheroni A., Mailland F., Caserini M., Mendling W. In vitro activity of nifuratel on vaginal bacteria: could it be a good candidate for the treatment of bacterial vaginosis? Antimicrob. Agents Сhemother. 2011; 55(5): 2490-2. https://dx.doi.org/10.1128/AAC.01623-10.
Конаныхина С.Ю., Сердюк О.А. Эффективность применения нифуратела при лечении дисбактериоза у детей. Вопросы практической педиатрии. 2006; 1(4): 130-3. [Konanykhina S.Yu., Serdyuk O.A. The effectiveness of the use of nifuratel in the treatment of dysbiosis in children. Questions of practical pediatrics 2006;1(4): 130-3.(in Russian)].
Polish Gynecological Society Expert Group. Stanowisko Zespołu Ekspertów Polskiego Towarzystwa Ginekologicznego dotyczace preparatu Macmiror Complex 500 [Statement of the Polish Gynecological Society Expert Group on the use of Macmiror Complex 500]. Ginekol Pol. 2012; 83(12): 956-9. Polish.
Vodstrcil L.A., Muzny C.A., Plummer E.L., Sobel J.D., Bradshaw C.S. Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment. BMC Med. 2021; 19(1):194. https://dx.doi.org/10.1186/s12916-021-02077-3
Obiero J., Rulisa S., Ogongo P., Wiysonge C.S. Nifuratel‐Nystatin combination for the treatment of mixed infections of bacterial vaginosis, vulvovaginal candidiasis, and trichomonal vaginitis. Cochrane Database Syst. Rev. 2018; (4): CD013012. https://dx.doi.org/10.1002/14651858.CD013012.

Received 30.10.2023

Accepted 17.11.2023

Inna A. Apolikhina, Dr. Med. Sci., Professor, Head of the Department of Aesthetic Gynecology and Rehabilitation, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia; Professor of the Department of Obstetrics, Gynecology, Perinatology, and Reproductology,
Institute of Professional Education, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, +7(495)735-10-55, apolikhina@inbox.ru,
https://orcid.org/0000-0002-4581-6295, 117997, Russia, Moscow, Ac. Oparin str., 4.
Margarita R. Rakhmatulina, Dr. Med. Sci., Professor, Deputy Director for Organizational and Analytical Work, State Scientific Center for Dermatovenereology and Cosmetology, Ministry of Health of Russia, https://orcid.org/0000-0003-3039-7769, 107076, Russia, Moscow, Korolenko str., 3-6.
Tatyana V. Priputnevich, Dr. Med. Sci., Corresponding Member of the Russian Academy of Sciences, Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia,
https://orcid.org/0000-0002-4126-9730, 117997, Russia, Moscow, Ac. Oparin str., 4.
Elena A. Gorbunova, obstetrician-gynecologist, Researchrer at the Department of Aesthetic Gynecology and Rehabilitation, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russia, +7(495)531-44-44, el_gorbunova@oparina4.ru,
https://orcid.org/0000-0002-4723-4299, 117997, Russia, Moscow, Ac. Oparin str., 4.
Alexander E. Guschin, PhD, Leading Researcher, Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology, +7(916)144-05-56, aguschin1965@mail.ru, https://orcid.org/0000-0002-0399-1167, 119071, Russia, Moscow, Leninsky Ave., 17.
Nikolai N. Potekaev, Dr. Med. Sci., Professor, Director of the Moscow Scientific and Practical Center of Dermatovenerology and Cosmetology; Chief Specialist in dermatovenerology and cosmetology of the Ministry of Health of the Russian Federation; Chief Specialist in dermatovenerology and cosmetology of the Moscow Department of Health; Head of the Department of Skin Diseases and Cosmetology FDPO, N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia,
https://orcid.org/0000-0002-9578-5490
Igor I. Baranov, Dr. Med. Sci., Professor, Vice-President of the Russian Society of Obstetricians and Gynecologists, Head of the Organizational and Methodological Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia,
https://orcid.org/0000-0002-9813-2823, 117997, Russia, Moscow, Ac. Oparin str., 4.

Systematic review of the efficacy and safety of nifuratel for women with diseases accompanied by pathological discharge from the genital tract

Apolikhina I.A., Rakhmatulina М.R., Priputnevich Т.V., Gorbunova Е.А., Guschin А.Е., Potekaev N.N., Baranov I.I.

Keywords

References

About the Authors

Similar Articles