Opportunities for antimicrobial therapy of diseases accompanied by pathological discharge from the genital tract: results of the multicenter observational Prospectus program
Objective: To study the etiological pattern of diseases accompanied by pathological discharge from the genital tract in reproductive-aged women and to evaluate the efficacy and tolerability of Macmiror Complex (nifuratel + nystatin) in the treatment of these diseases in in the context of modern clinical practice.Apolikhina I.A., Guschin A.E., Efendieva Z.N., Tyulenev Yu.A.
Materials and methods: The prospective multicenter observational Prospectus program was implemented in 11 centers of 10 cities of the Russian Federation (Moscow, Saint Petersburg, Nizhny Novgorod, Voronezh, Stavropol, Kazan, Ufa, Novosibirsk, Yekaterinburg, and Vladivostok). To establish the etiology of diseases accompanied by pathological discharge from the genital tract, such as bacterial vaginosis, aerobic vaginitis, and vulvovaginal candidiasis, a molecular biological study was conducted using a procedure based on real-time PCR AmpliPrime-Floroscreen (NextBio LLC). The combined drug nifuratel + nystatin (Macmiror Complex, Polichem, Italy) as vaginal capsules was used for etiotropic therapy and the patients were followed up at 10, 30 and 90 days after the therapy. At 10-day follow-up, the clinical efficiency was evaluated using the clinical data (namely, relief of the signs and symptoms of the disease). Molecular biological control of the treatment was carried out at 30-day follow-ups. The drug’s tolerability (frequency of adverse events) and the number of relapses after a therapy cycle in the next three months were also analyzed.
Results: The investigation enrolled 93 patients with the established etiology of diseases accompanied by pathological discharge from the genital tract by PCR using the AmpliPrime-Floroscreen tests. The patients’ mean age was 32.9±7.7 years. The etiological pattern included diseases, such as bacterial vaginosis (35/93 (38%)), vulvovaginal candidiasis (21/93 (22%)), aerobic vaginitis (9/93 (10%)), and mixed vaginitis (28/93 (30%)). The clinical efficiency of the therapy was achieved in 94.6% of cases. During 3 months of follow-up, clinical relapses occurred in no more than 8.3% of cases. The molecular biological evaluation of the efficiency of treatment showed a positive result in 87.5% of cases. Excellent and good tolerances of Macmiror Complex were noted in 85.3% of cases; no allergic reactions were seen in 100% of cases.
Conclusion: The pattern of diseases accompanied by pathological discharge from the genital tract exhibits a high proportion of mixed diseases. Macmiror Complex has demonstrated high efficiency and good tolerance and therefore can be recommended for active clinical application in patients with diseases accompanied by pathological discharge from the genital tract, including mixed vaginitis.
Keywords
bacterial vaginosis
vulvovaginal candidiasis
aerobic vaginitis
mixed vaginal infections
empiric therapy
Macmiror Complex
nifuratel
nystatin
References
- Sherrard J., Wilson J., Donders G., Mendling W., Jensen J.S. 2018 European (IUSTI/WHO) International Union against sexually transmitted infections (IUSTI) World Health Organization (WHO) guideline on the management of vaginal discharge. Int. J. STD AIDS. 2018; 29(13): 1258-72. https://dx.doi.org/10.1177/0956462418785451.
- Lamont R.F., Morgan D.J., Wilden S.D., Taylor-Robinson D. Prevalence of bacterial vaginosis in women attending one of three general practices for routine cervical cytology. Int. J. STD AIDS. 2000; 11(8): 495-8. https://dx.doi.org/10.1258/0956462001916371.
- Mendling W., Mailland F. Microbiological and pharmaco-toxicological profile of nifuratel and its favourable risk/benefit ratio for the treatment of vulvo-vaginal infections. A review. Arzneimittelforschung. 2002; 52(1): 8-13. https://dx.doi.org/10.1055/s-0031-1299849.
- Бантьева М.Н., Суханова Л.П. Вопросы оптимизации амбулаторной акушерско-гинекологической службы. Социальные аспекты здоровья населения. Электронный научный журнал «Социальные аспекты здоровья населения». 2011; 3(19). Доступно по: http://vestnik.mednet.ru/content/view/309/30/lang,ru/ Дата обращения 07.12.2021. [Bantyeva M.N., Sukhanova L.P. Certain issues of optimization of obstetrician gynecological outpatient service. Electronic scientific journal "Social Aspects of Population Health". 2011; 3(19): electronic access http://vestnik.mednet.ru/content/view/309/30/lang,ru/ date of circulation 07.12.2021. (in Russian)].
- Mirmonsef P., Krass L., Landay A., Spear G.T. The role of bacterial vaginosis and trichomonas in HIV transmission across the female genital tract. Currю HIV Res. 2012; 10(3): 202-10. https://dx.doi.org/10.2174/157016212800618165.
- Sobel J.D., Subramanian C., Foxman B., Fairfax M., Gygax S.E. Mixed vaginitis-more than coinfection and with therapeutic implications. Curr. Infect. Dis. Rep. 2013; 15(2): 104-8. https://dx.doi.org/10.1007/s11908-013-0325-5.
- Румянцева Т.А., Сурсяков С.А., Хайруллина Г.А., Чернышова Л.А., Гущин А.Е. Вагинальные выделения у пациенток гинекологического профиля: этиология и подходы к диагностике. Акушерство и гинекология. 2015; 8: 96-101. [Rumyantseva T.A., Sursyakov V.A., Khairullina G.A., Chernyshova L.A., Gushchin A.E. Vaginal discharge in gynecological patients: Etiology and approaches to diagnosis. Obstetrics and Gynecology. 2015; 8: 96-101. (in Russian)].
- Schwiertz A., Taras D., Rusch K., Rusch V. Throwing the dice for the diagnosis of vaginal complaints? Ann. Clin. Microbiol. Antimicrob. 2006; 5: 4. https://dx.doi.org/10.1186/1476-0711-5-4.
- Verstraelen H., Swidsinski A. The biofilm in bacterial vaginosis: implications for epidemiology, diagnosis and treatment. Curr. Opin. Infect. Dis. 2013; 26(1): 86-9. https://dx.doi.org/10.1097/QCO.0b013e32835c20cd.
- Unemo M., Bradshaw C.S., Hocking J.S., de Vries H.J.C., Francis S.C., Mabey D. et al. Sexually transmitted infections: challenges ahead. Lancet Infect. Dis. 2017; 17(8): e235-79. https://dx.doi.org/10.1016/S1473-3099(17)30310-9.
- Muñoz-Barreno A., Cabezas-Mera F., Tejera E., Machado A. Comparative effectiveness of treatments for bacterial vaginosis: A network meta-analysis. Antibiotics (Basel). 2021; 10(8): 978. https://dx.doi.org/10.3390/antibiotics10080978.
- Sobel J.D., Schmitt C., Meriwether C. Long-term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin. J. Infect. Dis. 1993; 167(3): 783-4. https://dx.doi.org/https://dx.doi.org/10.1093/infdis/167.3.783.
- Bradshaw C.S., Morton A.N., Hocking J., Garland S.M., Morris M.B., Moss L.M. et al. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J. Infect. Dis. 2006; 193(11): 1478-86. https://dx.doi.org/10.1086/503780.
- 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 Chemother. 2011; 55(5): 2490-2. https://dx.doi.org/10.1128/AAC.01623-10.
- Бальмер Дж. и Группа мультицентрового исследования. Комбинация нифуратела и нистатина (Макмирор Комплекс) в лечении вульвовагинитов, вызванных смешанной грибковой, бактериальной и трихомонадой инфекцией. Медико-социальные проблемы семьи. 2012; 17(3-4): 30-3. [Balmer J. and Multicenter Research Group. Combination of nifuratel and nistatin (Macmiror Complex) in the treatment of vulvovaginitis caused by mixed fungal, bacterial and trichomonade infection. Medical and social problems of the family. 2012; 1: 1-9. (in Russian)].
- Jahić M., Balić A., Nurkić M., Dragović J., Adzajlić A., Habibović A. et al. Local combined therapy of vaginal infections by nifuratel-nistatin. Med. Glas (Zenica). 2010; 7(1): 86-8. (Croatian).
- 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 vilvovaginitis: selection of a drug for rational therapy. Questions of Gynecology, Obstetrics and Perinatology. 2004; 3(4): 27-31. (in Russian)].
- Серов В.Н., Шаповаленко С.А. Рациональная терапия вульвовагинитов смешанной этиологии и профилактика рецидивов. РМЖ. 2003; 16: 946-50. [Serov V.N., Shapovalenko S.A. Rational therapy of mixed etiology vulvovaginitis and relapse prevention. Russian Medical Journal. 2003; 16:946-50. (in Russian)].
- Swidsinski A., Guschin A., Tang Q., Dörffel Y., Verstraelen H., Tertychnyy A. et al. Vulvovaginal candidiasis: histologic lesions are primarily polymicrobial and invasive and do not contain biofilms. Am. J. Obstet. Gynecol. 2019; 220(1): 91. e1-91. e8. https://dx.doi.org/10.1016/j.ajog.2018.10.023.
- Ponde N.O., Lortal L., Ramage G., Naglik J.R., Richardson J.P. Candida albicans biofilms and polymicrobial interactions. Crit. Rev. Microbiol. 2021; 47(1): 91-111. https://dx.doi.org/10.1080/1040841X.2020.1843400.
- 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.
- Перламутров Ю.Н., Гомберг М.А., Чернова Н.И., Бочкова О.И., Щербо С.Н. 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. Questions of Gynecology, Obstetrics and Perinatology. 2011; 10(3): 22-5. (in Russian)].
- Российское общество акушеров-гинекологов. Клинические рекомендации по диагностике и лечению заболеваний, сопровождающихся патологическими выделениями из половых путей женщин. М.; 2019. 20c. [Russian Society of Obstetricians and Gynaecologists. Clinical guidelines for the diagnosis and treatment of diseases accompanied by pathological secretions from the female genital tract. M.: 2019. 20 p. (in Russian)].
- 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. https://dx.doi.org/10.1055/0031-1299958.
- Liang Q., Li N., Song S., Zhang A., Li N., Duan Y. High-dose nifuratel for simple and mixed aerobic vaginitis: A single-center prospective open-label cohort study. J Obstet Gynaecol Res. 2016; 42(10): 1354-60. https://dx.doi.org/10.1111/jog.13052.
- Румянцева Т.А., Сурсяков В.А., Хайруллина Г.А., Чернышова Л.А., Гущин А.Е. Вагинальные выделения у пациенток гинекологического профиля: этиология и подходы к диагностике. Акушерство и гинекология. 2015. 8: 96-101. [Rumyantseva T.A., Sursyakov V.A., Khairullina G.A., Chernyshova L.A., Gushchin A.E. Vaginal discharge in gynecological patients: Etiology and approaches to diagnosis. Obstetrics and Gynecology. 2015. 8: 96-101. (in Russian)].
- Доброхотова Ю.Э., Бондаренко К.Р., Гущин А.Е., Румянцева Т.А., Долгова Т.В., Кузнецов П.А., Джохадзе Л.С. Результаты исследования цервико-вагинальной микробиоты методом ПЦР в реальном времени у беременных с угрожающими преждевременными родами. Акушерство и гинекология. 2018. 11: 50-9. https://dx.doi.org/10.18565/aig.2018.11.50-59. [Dobrokhotova Yu.E., Bondarenko K.R., Gushchin A.E., Rumyantseva T.A., Dolgova T.V., Kuznetsov P.A., Dzhokhadze L.S. The results of the examination of cervical-vaginal microbiota in pregnant women with threatened preterm birth using a real-time polymerase chain reaction. Obstetrics and Gynecology. 2018. 11: 50-9. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.11.50-59.
- Кира Е.Ф., Роговская С.И., Артымук Н.В., Савичева А.М., Гущин А.Е., Румянцева Т.А., Иванова О.В. Результаты изучения эффективности и безопасности вагинального применения орнидазола при лечении бактериального вагиноза. Акушерство и гинекология. 2015; 8: 89-95. [Kira E.F., Rogovskaya S.I., Artymuk N.V., Savicheva A.M., Gushchin A.E., Rumyantseva T.A., Ivanova O.V. Results of the study of the efficiency and safety of vaginal ornidazole in the treatment of bacterial vaginosis. Obstetrics and Gynecology. 2015; 8: 89-95. (in Russian)].
- Страчунский Л.С., Белоусов Ю.Б., Козлов С.Н., ред. Практическое руководство по антиинфекционной химиотерапии. Смоленск; 2007. 420c. [29. Strachunsky L.S., Belousov Yu.B., Kozlov S.N. Practical guide on anti-infectious chemotherapy. Pharmacology; 2007. 420 p. (in Russian)].
Received 14.12.2021
Accepted 20.12.2021
About the Authors
Inna A. Apolikhina, MD, PhD, Head of the Department of Aesthetic Gynecology and Rehabilitation, Academician V.I. Kulakov NMRC for OG&P, Ministry of Health of Russia; Professor of the Department of Obstetrics, Gynecology, Perinatology, and Reproductology, Institute of Professional Education, I.M. Sechenov First MSMU,Ministry of Health of Russia (Sechenov University), i_apolikhina@oparina4.ru, 117997, Russia, Moscow, Oparina str., 4.
Alexander E. Guschin, Ph.D. (Bio), Leading Researcher, Moscow Scientific and Practical Center for Dermatovenerology and Cosmetology, Moscow Department of Health, aguschin1965@mail.ru, 119071, Russia, Moscow, Leninsky Ave., 17.
Zulfia N. Efendieva, Ph.D., obstetrician-gynecologist at the Department of Aesthetic Gynecology and Rehabilitation, Academician V.I. Kulakov NMRC for OG&P,
Ministry of Health of Russia, efendievaz@yandex.ru, 117997, Russia, Moscow, Oparina str., 4.
Yuri A. Tyulenev, Ph.D. (Bio), Junior Researcher at the Department of Anogenital Dermatoses and Sexually Transmitted Infections, MNPCDK, Moscow Department of Health, tulenevsk@gmail.com, 119071, Russia, Moscow, Leninsky Ave., 17.
Authors’ contributions: Apolikhina I.A., Guschin A.E., Efendieva Z.N., Tyulenev Yu.A. – development of the concept and design of publications on the topic of the article, data analysis, writing the text of the manuscript, approval of the manuscript for publication.
Conflicts of interest: The authors declare that there are no conflicts of interest.
Funding: The article has been prepared without sponsorship.
Acknowledgment: The authors express their gratitude to Prof. Alevtina M. Savicheva, MD; Prof. Irina N. Korotkikh, MD;
Prof. Indira V. Sakhautdinova, MD; Prof. Vitaly M. Kuleshov, MD; Irina N. Kononova, MD; Tatiana I. Rumyantseva, PhD.;
Rusudan M. Ionova, PhD; Olga V. Danilova, PhD; Lyudmila S. Matyushkina, PhD; Olga A. Pauzina for participation
in the observational Prospectus program.
Patients’ Consent to Publication. All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement. The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: 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.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2021; 12: 167-176 (in Russian)
https://dx.doi.org/10.18565/aig.2021.12.167-176
Similar Articles
