Therapeutic approaches in the treatment of vulvovaginal candidiasis

According to world statistics, vulvovaginal candidiasis is a very common disease with a serious tendency to recurrence and chronic-ity, which makes it a fundamentally significant medical and social problem, the solution of which is becoming a priority task facing obstetricians and gynecologists. The attention of doctors should be focused on the search for optimal treatment regimens that meet all the requirements for therapeutic approaches, the introduction of which into clinical practice should lead to a significant decrease in the incidence of the disease and its chronicity in the population, and also on increase in the relapse interval, which will certainly be reflected in improving the quality of life of women. Analysis and comparison of the effectiveness of antifungal drugs on the modern pharmaceutical market, and the choice of the most effective and safe drug can be the key to success in combating the widespread prevalence of vulvovaginal candidiasis.

The article presents the etiological aspects of vulvovaginal candidiasis, demonstrating an increase in the importance of Candida non-albicans in the pathogenesis of the disease, which is confirmed by high rates of disease prevalence, including chronic and recurrent forms. The mechanisms of vulvovaginal candidiasis development and diagnostic methods that allow to assess the state of vaginal microcenosis most adequately are considered. The negative impact of vulvovaginal candidiasis on the course of pregnancy and possible outcomes for both the mother and the fetus are also described. Special attention is paid to the ability of fungi of the genus Candida to form associations of microorganisms - biofilms, which create an obstacle to many antifungal drugs. The problem of resistance of Candida fungi to a number of antifungal drugs is highlighted. Data on the uniqueness of the composition and action of sertaconazole and the effectiveness of its use, which is confirmed by studies, including in a group of pregnant patients, are presented. The article analyses indicators of safety of sertaconazole and criteria of continuity.

1. Bayramova G.R., Baranov I.I., Priputnevich T.V., Chernova V.F. Combined methods of baceteriaL vaginosis treatment in adolescents. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie = Obstetrics and Gynecology: News, Opinions, Training. 2017;(4):63-69. (In Russ.) Available at: https://cyber-Leninka.ru/articLe/n/vuLvovaginaLnyy-kandidoz-kLinicheskie-i-terapevtich-eskie-aspekty-v-praktike-akushera-ginekoLoga/viewer.

2. Khashukoeva A.Z., KhLynova S.A., KercheLaeva S.B. Genitourinary infections in women: new opportunities for effective combined therapy. Akusherstvo i ginekologiya = Obstetrics and Gynegology. 2019;(11):221-225. (In Russ.) doi: 10.18565/aig.2019.11.221-225.

3. Abbasi Nejat Z., Farahyar S., FaLahati M., Ashrafi Khozani M., Hosseini A.F., Faiazy A. et aL. MoLecuLar identification and antifungaL susceptibiLity pattern of non-aLbicans Candida species isoLated from vuLvovaginaL candidiasis. Iran BiomedJ. 2017;22(1):33-41. doi: 10.22034/ibj.22.1.33.

4. PriLepskaya V.N., Kira E.F., ApoLikhina I.A., Bayramova G.R., Gomberg M.A., Minkina G.N. et aL. Clinical guidelines for the diagnosis and treatment of diseases accompanied by abnormal vaginal discharge. 2th ed. Moscow; 2019. 56 p. (In Russ.) AvaiLabLe at: https://minzdrav.miduraL.ru/upLoads/19.pdf.

5. PriLepskaya V.N., Bayramova G.R. Vulvovaginal candidiasis: symptoms, diagnosis, therapy strategy. Moscow: GEOTAR-Media; 2010. 72 p. (In Russ.)

6. Rathod S.D., BuffLer P.A. HighLy-cited estimates of the cumuLative incidence and recurrence of vuLvovaginaL candidiasis are inadequateLy documented. BMC Women's Health. 2014;14(1):43. doi: 10.1186/1472-6874-14-43.

7. Khashukoeva A.Z., Agaeva Z.A., Agaeva M.I. A strategy to reduce the recurrence rate of vaginaL candidiasis in women with weakened immunity. Akusherstvo i ginekologiya = Obstetrics and Gynegology. 2018;(12):88-92. (In Russ.) doi: 10.18565/aig.2018.12.88-92.

8. Denning D.W., KneaLe M., SobeL J.D., Rautemaa-Richardson R. GLobaL burden of recurrent vuLvovaginaL candidiasis: a systematic review. Lancet Infect Dis. 2018;18(11):e339-e347. doi: 10.1016/S1473-3099(18)30103-8.

9. Pestrikova T.Yu., Yurasova E.A., KoteLnikova A.V. VuLvovaginaL candidiasis: modern Look at the probLem. RMZh. Mat’ i ditya = RMJ. Mother and child. 2017;25(26):1965-1970. (In Russ.) AvaiLabLe at: https://www.rmj.ru/arti-cLes/ginekoLogiya/VuLyvovaginaLynyy_kandidoz_sovremennyy_vzgLyad_na_probLemu_1/#ixzz6Z34iLOWM.

10. VaLe-SiLva L.A., SangLard D. Tipping the baLance both ways: drug resistance and viruLence in Candida gLabrata. FEMS Yeast Res. 2015;15(4):fov025. doi: 10.1093/femsyr/fov025.

11. Szweda P., Gucwa K., Romanowska E., Dzierz Anowska-Fangrat K., Naumiuk L., BriLLowska-Da A. et aL. Mechanisms of azoLe resistance among cLinicaL isoLates of Candida gLabrata in PoLand. J Med Microbiol. 2015;64(6):610-619. doi: 10.1099/jmm.0.000062.

12. MiLLs B.B. Vaginitis: Beyond the basics. Obstet Gynecol Clin North Am. 2017;44(2):159-177. doi: 10.1016/j.ogc.2017.02.010.

13. Workowski K.A., BoLan G.A. SexuaLLy transmitted diseases treatment guideLines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137. AvaiLabLe at: https://pubmed.ncbi.nLm.nih.gov/26042815.

14. Rudneva O.D., Dobretsova T.A., MakLetsova S.A.; Radzinskiy V.E. (ed.) Relapses of bacvaginosis and lactoflora: from pressing ambiguity to practical solutions. Moscow: StatusPraesens; 2013. 16 p. (In Russ.) AvaiLabLe at: https://oLd.praesens.ru/opubLikovano-informatsionnoe-pismo.

15. Nazarova N.M., Nekrasova M.E., DovLetkhanova E.R., Abakarova PR. Vaginitis and cervicitis: choice of an effective therapy method (Literature review). Meditsinskiysovet = Medical Council. 2020;(3):17-23. (In Russ.) doi: 10.21518/2079-701X-2020-3-17-23.

16. GongaLves B., Ferreira C., ALves C.T., Henriques M., Azeredo A., SiLva S. VuLvovaginaL candidiasis: EpidemioLogy, microbioLogy and risk factors. Crit Rev Microbiol. 2016;42(6):905-927. doi: 10.3109/1040841X.2015.1091805.

17. ParoLin C., Marangoni A., Laghi L., Foschi C., Nahui PaLomino RA., CaLonghi N. et aL. IsoLation of VaginaL LactobaciLLi and Characterization of Anti-Candida Activity. PLoS One. 2015;10(6):e0131220. doi: 10.1371/journaL. pone.0131220.

18. AntonopouLou S., Aoun M., ALexopouLos C.E., Baka S., Logothetis E., KaLambokas T. et aL. FenticonazoLe activity measured by the methods of the European Committee on AntimicrobiaL SusceptibiLity Testing and CLSI against 260 Candida vuLvovaginitis isoLates from two European regions and annotations on the prevaLent genotypes. Antimicrob Agents Chemother. 2009;53(5):2181-2184. doi: 10.1128/AAC.01413-08.

19. Ankirskaya A.S., Muravieva V.V. IntegraL assessment of the condition of the vaginaL microbiota. diagnosis of opportunistic vaginitis. Akusherstvo i gine-kologiya: novosti, mneniya, obuchenie = Obstetrics and Gynecology: News, Opinions, Training. 2020;8(1):69-76. (In Russ.) doi: 10.24411/2303-9698-2020-11009.

20. Roberts C.L., Rickard K., Kotsiou G., Morris J.M. Treatment of asymptomatic vaginaL candidiasis in pregnancy to prevent preterm birth: an open-LabeL piLot randomized controLLed triaL. BMC Pregnancy Childbirth. 2011;(11):18. doi: 10.1186/1471-2393-11-18.

21. Efendieva Z.N. SertaconazoLe in the treatment of vuLvovaginaL candidiasis. Meditsinskiy sovet = Medical Council. 2019;(13):94-98. (In Russ.) doi: 10.21518/2079-701X-2019-13-94-98.

22. CzeizeL A.E., FLadung B., Vargha P. Preterm birth reduction after cLotrimazoLe treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol. 2004;116(2):157-163. doi: 10.1016/j.ejogrb.2004.02.011.

23. Pinhat E.C., Borba M.G.S., Ferreira M.L., Ferreira M.A., Fernandes R.K., NicoLaou S.K. et aL. FungaL coLonization in newborn babies of very Low birth weight: a cohort study. J Pediatr (Rio J). 2012;88(3):211-216. doi: 10.2223/JPED.2192.

24. Cauchie M., Desmet S., Lagrou K. Candida and its duaL LifestyLe as a commensaL and a pathogen. Res Microbiol. 2017;168(9-10):802-810. doi: 10.1016/j.resmic.2017.02.005.

25. SeLvan Т., Girisha G., Vijaybhaskar, Suthakaran R. Comparative evaLuation of newer topicaL antifungaL agents in the treatment of superficiaL fungaL infections (tinea or dermatophytic). Int Res J Pharmy. 2013;4(6):224-228. doi: 10.7897/2230-8407.04651.

26. Verma K., Bhat M., Baniya G.C. A comparative study of antifungaL activity of topicaL per vaginaL appLication of tabLet sertaconazoLe and cLotrimazoLe in cases of vuLvovaginaL candidiasis. Int J Health Sci Res. 2015;5(2):111-115. AvaiLabLe at: https://www.semanticschoLar.org/paper/A-Comparative-Study-of-AntifungaL-Activity-of-Per-Verma-Bhat/b9c203b3ff9e02f6b820d3beea1fffcd6cbce5c0.

27. PaLacin C., Tarrago C., Agut J., GugLietta A. In vitro activity of sertaconazoLe, fLuconazoLe, ketoconazoLe, fenticonazoLe, cLotrimazoLe and itraconazoLe against pathogenic vaginaL yeast isoLates. Methods Find Exp Clin Pharmacol. 2001;23(2):61-64. doi: 10.1358/mf.2001.23.2.627926.

28. Kashevarov D.F., Vorontsova I.V LocaL therapy of vuLvovaginaL candidiasis. RMZh. Mat’ i ditya = Russian Medical Journal. Mother and Child. 2014;(19):1394. (In Russ.) AvaiLabLe at: https://www.rmj.ru/articLes/gine-koLogiya/Mestnaya_terapiya_vuLyvovaginaLynogo_kandidoza.

29. Voznesenskaya N.V., Kharitonov V.M., Burganova R.F., Istomina N.S., Saakyan G.K. SertaconazoL (zaLain) in the treatment of vaginaL candida during pregnancy. Ul'yanovskiy mediko-biologicheskiy zhurnal = Ulyanovsk Medico-Biological Journal. 2013;(2):36-39. (In Russ.) AvaiLabLe at: https://cyberLeninka.ru/articLe/n/sertakonazoL-zaLain-v-Lechenii-vuLvovaginaLno-go-kandidoza-u-beremennyh/viewer.

30. Gasparyan S.A., Khazhbiev A.A., Ryzhkov V.V. Experience with sertaconazoLe in pregnant women with vuLvo-vaginaL candidiasis. Meditsinskiy sovet = Medical Council. 2019;(13):160-165. (In Russ.) doi: 10.21518/2079-701X-2019-13-160-165.

31. PaLacin C., Tarrago C., Ortiz J.A. SertaconazoLe: pharmacoLogy of a gynecoLogicaL antifungaL agent. Int J Gynaecol Obstet. 2000;71(S1):37-46. doi: 10.1016/S0020-7292(00)00351-9.

32. Kaur S., Sur R., LiebeL F.T., SouthaLL M.D. Induction of ProstagLandin D2 through the p38 MAPK Pathway Is ResponsibLe for the Antipruritic Activity of SertaconazoLe Nitrate. J Invest Dermatol. 2010;130(10):2448-2456. doi: 10.1038/jid.2010.152.

33. Khamaganova I.V. TopicaL therapy for vuLvovaginaL candidiasis. Akusherstvo i ginekologiya = Obstetrics and Gynegology. 2012;(4-2):122-124. (In Russ.) Available at: https:://aig-jQurnaL.ru/articLes/Mestnaya-terapiya-vuLvovaginaLnogo-kandidoza.htmL

34. Mondello F., De Bernardis F., Girolamo A., Cassone A., Salvatore G. In vivo activity of terpinen-4-ol, the main bioactive component of Melaleuca alternifolia Cheel (tea tree) oil against azole-susceptible and -resistant human pathogenic Candida species. BMC Infect Dis. 2006;6:158. doi: 10.1186/1471-2334-6-158.

35. Hammer K.A., Carson C.F., Riley T.V. In vitro susceptibilities of lactobacilli and organisms associated with bacterial vaginosis to Melaleuca alternifo-lia (tea tree) oil. Antimicrob Agents Chemother. 1999;43(1):196. doi: 10.1128/AAC.43.1.196.

36. Astani A., Reichling J., Schnitzler P. Comparative study on the antiviral activity of selected monoterpenes derived from essential oils. Pythother Res. 2010;24(5):673-679. doi: 10.1002/ptr.2955.

37. Carson C.F., Hammer K.A., Riley T.V. Melaleuca alternifolia (Tea Tree) oil: a review of antimicrobial and other medicinal properties. Clin Microbiol Rev. 2006;19(1):50-62. doi: 10.1128/CMR.19.1.50-62.2006.

38. Ignatovsky A.V., Sokolovsky E.V. New possibilities in therapy of pathology of the vulva and the vagina. Zhurnal akusherstva i zhenskikh bolezney = Journal of Obstetrics and Women’s Diseases. 2009;58(1):56-59. (In Russ.) Available at: https://elibrary.ru/item.asp?id=12807050.