Effectiveness of the combined drug ternidazole–neomycin sulfate–nystatin–prednisolone in topical therapy of vaginal dysbiosis associated with Atopobium vaginae in nonpregnant and pregnant women with reproductive failure

Authors

DOI:

https://doi.org/10.18370/2309-4117.2024.74.55-72

Keywords:

reproductive failure, recurrent implantation failures, vaginal dysbiosis, bacterial vaginosis, aerobic vaginitis, aerobic-anaerobic dysbiosis, Atopobium vaginae, treatment, combined drug, ternidazole– neomycin sulfate–nystatin–prednisolone

Abstract

Background. Atopobium vaginae is an important component of the complex abnormal anaerobic vaginal microflora in vaginal dysbiosis and is believed to be at least partially responsible for known adverse gynecological and obstetric outcomes. Resistance of A. vaginae to traditional therapy (metronidazole and clindamycin) is described.
Objective of the study: to evaluate the effectiveness of topical therapy with the combined drug ternidazole–neomycin sulfate–nystatin–prednisoloneof vaginal dysbiosis associated with A. vaginae in diagnostically significant concentrations in non-pregnant and pregnant women of reproductive age with a history of reproductive failure.
Materials and methods. 78 women of reproductive age with vaginal dysbiosis associated with A. vaginae in diagnostically significant concentrations were under observation. 37 infertile women had recurrent implantation failures and 41 pregnant women with infertility treated in cycles of assisted reproductive technologies. Control groups consisted of 30 fertile non-pregnant women and 30 pregnant women after natural conception with vaginal normocenosis. Comprehensive quantitative assessment of the vaginal anaerobic microbiota was performed using real-time polymerase chain reaction.
Results. A. vaginae in diagnostically significant concentrations in the vaginal microbiota in the vast majority of cases is accompanied by the presence of Gardnerella vaginalis and other co-pathogens, mixed infections. Every second woman has aerobic-anaerobic dysbiosis, which makes it advisable to use combined topical drugs. The use of ternidazole–neomycin sulfate–nystatin–prednisolone vaginal tablets resulted in the absence of facultative and obligate anaerobes, Ureaplasma (urealiticum + parvum) and Candida spp. in the vaginal microbiota in diagnostically significant concentrations in women of treated groups. The average relative content of none of the studied conditionally pathogenic microorganisms after treatment did not exceed -3 CFU.
Conclusions. The combined vaginal drug ternidazole–neomycin sulfate–nystatin–prednisolone is a highly effective, safe and compliant remedy for restoring vaginal health in non-pregnant and pregnant women with a history of reproductive failure and vaginal dysbiosis associated with the presence of A. vaginae in diagnostically significant concentrations.

Author Biographies

O.M. Nosenko, Odesa National Medical University, Odesa

MD, professor, Obstetrics and Gynecology Department

F.O. Khancha, LLC «Clinic of Reproductive Medicine «Nadia Odesa», Odesa

PhD, obstetrician gynecologist

R.Y. Demydchyk, Odesa National Medical University, Odesa

Postgraduate student, Obstetrics and Gynecology Department

References

  1. Abou Chacra L, Fenollar F, Diop K. Bacterial Vaginosis: What Do We Currently Know? Front Cell Infect Microbiol. 2022 Jan 18;11:672429. DOI: 10.3389/fcimb.2021.672429.
  2. Castro J, Rosca AS, Cools P, et al. Gardnerella vaginalis Enhances Atopobium vaginae Viability in an in vitro Model. Front Cell Infect Microbiol. 2020 Mar 4;10:83. DOI: 10.3389/fcimb.2020.00083.
  3. Kairys N, Garg M. Bacterial Vaginosis. In: StatPearls. (Treasure Island (FL): StatPearls Publishing; 2017); 2021.
  4. Farr A, Swidsinski S, Surbek D, et al. Bacterial Vaginosis: Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/028, June 2023). Geburtshilfe Frauenheilkd. 2023 Nov 3;83(11):1331-1349. DOI: 10.1055/a-2169-8539.
  5. Castro J, Rosca AS, Muzny CA, Cerca N. Atopobium vaginae and Prevotella bivia Are Able to Incorporate and Influence Gene Expression in a Pre-Formed Gardnerella vaginalis Biofilm. Pathogens. 2021 Feb 20;10(2):247. DOI: 10.3390/pathogens10020247.
  6. Lakhno IV. Modern possibilities of diagnosing disorders of the condition of the vaginal biotope. With care for the woman. 2020;1-2:103-104.
  7. Mendling W, Palmeira-de-Oliveira A, Biber S, Prasauskas V. An update on the role of Atopobium vaginae in bacterial vaginosis: what to consider when choosing a treatment? A mini review. Arch Gynecol Obstet. 2019 Jul;300(1):1-6. DOI: 10.1007/s00404-019-05142-8.
  8. Collins MD, Wallbanks S. Comparative sequence analyses of the 16S rRNA genes of Lactobacillus minutus, Lactobacillus rimae and Streptococcus parvulus: proposal for the creation of a new genus Atopobium. FEMS Microbiol Lett. 1992 Aug 15;74(2-3):235-40. DOI: 10.1016/0378-1097(92)90435-q.
  9. Rodriguez Jovita M, Collins MD, Sjödén B, Falsen E. Characterization of a novel Atopobium isolate from the human vagina: description of Atopobium vaginae sp. nov. Int J Syst Bacteriol. 1999 Oct;49 Pt 4:1573-6. DOI: 10.1099/00207713-49-4-1573.
  10. Fernández-Edreira D, Liñares-Blanco J, V-Del-Río P, Fernandez-Lozano C. VIBES: A consensus subtyping of the vaginal microbiota reveals novel classification criteria. Comput Struct Biotechnol J. 2023 Nov 30;23:148-156. DOI: 10.1016/j.csbj.2023.11.050.
  11. Hardy L, Jespers V, Abdellati S, et al. A fruitful alliance: the synergy between Atopobium vaginae and Gardnerella vaginalis in bacterial vaginosis-associated biofilm. Sex Transm Infect. 2016 Nov;92(7):487-491. DOI: 10.1136/sextrans-2015-052475.
  12. Swidsinski A, Mendling W, Loening-Baucke V, et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol. 2005 Nov;106(5 Pt 1):1013-23. DOI: 10.1097/01.AOG.0000183594.45524.d2.
  13. Redelinghuys MJ, Ehlers MM, Bezuidenhoudt JE, et al. Assessment of Atopobium vaginae and Gardnerella vaginalis concentrations in a cohort of pregnant South African women. Sex Transm Infect. 2017 Sep;93(6):410-415. DOI: 10.1136/sextrans-2016-052883.
  14. Afolabi BB, Moses OE, Oduyebo OO. Bacterial Vaginosis and Pregnancy Outcome in Lagos, Nigeria. Open Forum Infect Dis. 2016 Feb 9;3(1):ofw030. DOI: 10.1093/ofid/ofw030.
  15. Brown RG, Marchesi JR, Lee YS, et al. Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin. BMC Med. 2018 Jan 24;16(1):9. DOI: 10.1186/s12916-017-0999-x.
  16. Dos Anjos Borges LG, Pastuschek J, Heimann Y, et al. Vaginal and neonatal microbiota in pregnant women with preterm premature rupture of membranes and consecutive early onset neonatal sepsis. BMC Med. 2023 Mar 13;21(1):92. DOI: 10.1186/s12916-023-02805-x.
  17. Datsomor EA, Zubach O, Prykuda N, Zinchuk A. A case report of septic gardnerellosis. IDCases. 2021 Mar 10;24:e01069. DOI: 10.1016/j.idcr.2021.e01069.
  18. Zhang F, Zhang T, Ma Y, et al. Alteration of vaginal microbiota in patients with unexplained recurrent miscarriage. Exp Ther Med. 2019 May;17(5):3307-3316. DOI: 10.3892/etm.2019.7337.
  19. Odogwu NM, Chen J, Onebunne CA, et al. Predominance of Atopobium vaginae at Midtrimester: a Potential Indicator of Preterm Birth Risk in a Nigerian Cohort. mSphere. 2021 Jan 27;6(1):e01261-20. DOI: 10.1128/mSphere.01261-20.
  20. Abbe C, Mitchell CM. Bacterial vaginosis: a review of approaches to treatment and prevention. Front Reprod Health. 2023 May 31;5:1100029. DOI: 10.3389/frph.2023.1100029.
  21. Bradshaw CS, Tabrizi SN, Fairley CK, et al. The association of Atopobium vaginae and Gardnerella vaginalis with bacterial vaginosis and recurrence after oral metronidazole therapy. J Infect Dis. 2006 Sep 15;194(6):828-36. DOI: 10.1086/506621.
  22. Raba G, Durkech A, Malík T, et al. Efficacy of Dequalinium Chloride vs Metronidazole for the Treatment of Bacterial Vaginosis: A Randomized Clinical Trial. JAMA Netw Open. 2024 May 1;7(5):e248661. DOI: 10.1001/jamanetworkopen.2024.8661. 40
  23. Polatti F. Bacterial vaginosis, Atopobium vaginae and nifuratel. Curr Clin Pharmacol. 2012 Feb 1;7(1):36-40. DOI: 10.2174/157488412799218824.
  24. Khomyak NV, Mamchur VI. Vaginitis: possibilities and advantages of combined local therapy. Medical aspects of women’s health. 2019; 4-5 (125-126):46-54.
  25. Dubossary YuA, Dubossary ZM. Terzhinan is the drug of choice in the treatment of bacterial vaginosis. Women’s health. 2012; 6 (72): 147-152.
  26. Mamchur VI, Dronov SN. Terzhinan eyes pharmacologist: an innovative approach to the therapy of vaginitis of different genesis. Medical aspects of women’s health. 2015; 9: 50–57.
  27. Kogan BG, Bondarenko YG. Nitroimidazoles yesterday and today: 50 years in the fight against trichomoniasis. Women’s reproductive health. 2007; 5 (34): 13–19.
  28. Choukri F, Benderdouche M, Sednaoui P. In vitro susceptibility profile of 200 recent clinical isolates of Candida spp. to topical antifungal treatments of vulvovaginal candidiasis, the imidazoles and nystatin agents. J Mycol Med. 2014 Dec;24(4):303–7. DOI: 10.1016/j.mycmed.2014.05.001.
  29. San Juan Galán J, Poliquin V, Gerstein AC. Insights and advances in recurrent vulvovaginal candidiasis. PLoS Pathog. 2023 Nov 10;19(11):e1011684. DOI: 10.1371/journal.ppat.1011684.
  30. Compendium-2011 – medicinal products: in 2 volumes. Ed. V. M. Kovalenko, O. P. Viktorova. K.: MORION, 2011. 1760 p.
  31. Savicheva AM, Spasibova EV. Effect of the combined drug Terzhinan® on microorganisms isolated from the urogenital tract of women. In vitro experiment. Journal of Obstetrics and Women’s Diseases. 2017; LXVI;5(66):21-26.
  32. Vdovichenko UP, Gopchuk OM. Terzhinan in obstetrics and gynecology practice. Women’s health. 2011;10(66):71-74.
  33. Comparative assessment of the activity of the constituent drugs Polygynax and Terzhinan in vitro (report of a study conducted in the Nosocotech laboratory (Lyon, France), December 15, 2011). Medical aspects of women’s health. 2012; 3(54):44-46.
  34. Mian DB, Loué VAS, Angoi AV, et al. Efficacity of ternidazole-neomycin sulfate-nystatin and prednisolone association in syndromic management of vaginitis in low and middle incomes countries. Int J Reprod Contracept Obstet Gynecol 2022;11(3):670-5. DOI: 10.18203/2320-1770.ijrcog20220543.
  35. Mian B, Okon G, Nigue L, et al. Management of vaginitis in limited-resource countries in sub-Saharan Africa. What place for the ternidazole, neomycin sulfate, nystatin and prednisolone association? Médecine d’Afrique Noire. 2018, Vol. 65, No. 12, 571–80.

Downloads

Published

2024-11-29

How to Cite

Nosenko, O., Khancha, F., & Demydchyk, R. (2024). Effectiveness of the combined drug ternidazole–neomycin sulfate–nystatin–prednisolone in topical therapy of vaginal dysbiosis associated with Atopobium vaginae in nonpregnant and pregnant women with reproductive failure. REPRODUCTIVE ENDOCRINOLOGY, (74), 55–72. https://doi.org/10.18370/2309-4117.2024.74.55-72

Issue

No. 74 (2024)

Section

Drug therapy

License

Creative Commons License

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

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

    1. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.