Recurrent bacterial vaginosis: a variable approach taking into account possible pathogenetic aspects

Authors

  • N.F. Zakharenko SI Centre for Innovative Medical Technologies of the NAMS of Ukraine, Kyiv, Ukraine
  • I.P. Manoliak SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine
  • V.S. Solskiy SI «Institute of Pediatrics, Obstetrics and Gynecology named after academician O.M. Lukyanova of the NAMS of Ukraine», Kyiv, Ukraine

DOI:

https://doi.org/10.15574/HW.2023.167.5

Keywords:

women, bacterial vaginosis, complex treatment, probiotic, eubiotic strains

Abstract

Purpose - to evaluate the effectiveness, duration of the clinical result, safety and tolerability of the complex treatment of recurrent bacterial vaginosis (BV) with the sequential use of an antibacterial agent and probiotic suppositories.

Materials and methods. 91 women of reproductive age with a symptomatic course and a diagnosis of recurrent BV participated in the study. Primary decontamination of the vaginal tract was performed by all subjects and consisted of a 10-day intravaginal administration of the drug Terzhinan. Subsequently, the participants were randomized into three comparable groups. After primary remediation, no additional medication was prescribed to patients in the Group 1 (n=30). Subjects of the Groups 2 (n=30) and 3 (n=31) were recommended daily administration of vaginal probiotic suppositories Bifolak for a 10-day course, followed by prolongation of their use twice a week for 2 months in the Group 3. The effectiveness of BV therapy was evaluated immediately after antibacterial treatment and after a 6-month follow-up period based on the results of clinical examination, microscopic analysis of smears, and determination of vaginal pH with litmus strips.

Results. At the end of the 10-day course of vaginal sanitation, subjective and objective signs of bacterial infection were not detected among all study participants, the pH of the vaginal secretion was within physiological limits and did not differ statistically between the Groups. At the stage of the sixth month of observation, data from a gynecological examination, smear microscopy and pH-metry confirmed 4 recurrences of the disease in the Group 1. In the Group 2, whose women additionally received a ten-day course of probiotic therapy, the number of episodes of repeated development of the disease was significantly lower, and amounted to 1 case for the entire observation period. Patients of the Group 3 did not notice manifestations of reinfection during the study and had no objective signs of BV. The use of a probiotic for a continuous course of 10 days in the Group 2, as well as its prolongation in a maintenance regimen (twice a week for 2 months) in the Group 3, was combined with a stable normalization of the acidity of the vaginal secretion, which was evidenced by the preservation of optimal pH until the end of the observation period (4.07±0.14 and 3.94±0.17, respectively, in the Groups 2 and 3 against 4.43±0.14 in the Group 1, p<0.05). The complete absence of repeated cases of BV and the lower pH values (p>0,05) in the Group 3 allowed us to consider the greater anti-relapse effectiveness of the long-term use of the probiotic at the trend level.

Conclusions. Traditional schemes for the use of antibacterial agents in the treatment of BV allow to achieve a clinical and laboratory effect at the end of the course, but do not ensure its complete preservation for a long period of time. The disadvantage of the etiotropic approach to the treatment of BV is the lack of attention to the competitive properties of the indigenous flora as a factor in countering dysbiosis. Taking into account the pathogenetic essence of BV, which consists in the violation of the growth balance between conditionally pathogenic microorganisms and its own flora, classical antibacterial schemes can be successfully supplemented by the external introduction of eubiotic strains. Our study showed the benefits of complex therapy with an antibacterial agent and a probiotic, which consisted in stabilizing the acidity of the vaginal space and reducing the rate of disease recurrence, with a tendency to increase the effect in parallel with the duration of treatment.

The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies.

No conflict of interests was declared by the authors.

References

Alves P, Castro J, Sousa C, Cereija TB, Cerca N. (2014). Gardnerella vaginalis outcompetes 29 other bacterial species isolated from patients with bacterial vaginosis, using in an in vitro biofilm formation model. J Infect Dis. 210 (4): 593-596. https://doi.org/10.1093/infdis/jiu131; PMid:24596283

Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. (1983). Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 74: 14-22. https://doi.org/10.1016/0002-9343(83)91112-9; PMid:6600371

Anderson MR, Klink K, Cohrssen A. (2004). Evaluation of vaginal complaints. JAMA. 291: 1368-1379. https://doi.org/10.1001/jama.291.11.1368; PMid:15026404

Ankirskaya AS. (2000). Nonspecific vaginitis. Clinical microbiology and antimicrobial therapy. 2 (17): 29-31.

Aroutcheva AA, Simoes JA, Faro S. (2001). Antimicrobial protein produced by vaginal Lactobacillus acidophilus that inhibits Gardnerella vaginalis. Infect Dis Obstet Gynecol. 9 (1): 33-39. https://doi.org/10.1155/S1064744901000060; PMid:11368257 PMCid:PMC1784632

Austin M, Beigi R, Meyn L, Hillier S. (2005). Microbiologic response to treatment of bacterial vaginosis with topical clindamycin or metronidazole. J. Clin. Microbiol. 43: 4492-4497. https://doi.org/10.1128/JCM.43.9.4492-4497.2005; PMid:16145097 PMCid:PMC1234077

Beigi RH, Austin MN, Meyn LA, Krohn MA, Hillier SL. (2004). Antimicrobial resistance associated with the treatment of bacterial vaginosis. Am J Obstet Gynecol. 191: 1124-1129. https://doi.org/10.1016/j.ajog.2004.05.033; PMid:15507930

Borgdorff H, Gautam R, Armstrong SD et al. (2016). Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier. Mucosal Immunol. 9: 621-633. https://doi.org/10.1038/mi.2015.86; PMid:26349657

Boris J, Påhlson C, Larsson PG. (1997). Six years observation after successful treatment of bacterial vaginosis. Infect. Dis Obstet Gynecol. 5 (297): 302. https://doi.org/10.1002/(SICI)1098-0997(1997)5:4<297::AID-IDOG7>3.0.CO;2-U

Boris S, Suarez JE. Vazquez F, Barbes C. (1998). Adherence of human vaginal lactobacilli to vaginal epithelial cells and interaction with uropathogens. Infect Immun. 66 (5): 1985-1989. https://doi.org/10.1128/IAI.66.5.1985-1989.1998; PMid:9573080 PMCid:PMC108154

Briselden AM, Moncla BJ, Stevens CE, Hillier SL. (1992). Sialidases (neuraminidases) in bacterial vaginosis and bacterial vaginosis-associated microflora. J Clin Microbiol. 30: 663-666. https://doi.org/10.1128/jcm.30.3.663-666.1992; PMid:1551983 PMCid:PMC265128

Castro J, Machado D, Cerca N. (2019). Unveiling the role of Gardnerella vaginalis in polymicrobial Bacterial Vaginosis biofilms: the impact of other vaginal pathogens living as neighbors. ISME J. 13 (5): 1306-1317. https://doi.org/10.1038/s41396-018-0337-0; PMid:30670827 PMCid:PMC6474217

Cauci S. (2004). Vaginal Immunity in Bacterial Vaginosis. Curr Infect Dis Rep. 6: 450-456. https://doi.org/10.1007/s11908-004-0064-8; PMid:15538982

Chee WJY, Chew SY, Than LTL. (2020). Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health. Microb Cell Fact. 19: 203. https://doi.org/10.1186/s12934-020-01464-4; PMid:33160356 PMCid:PMC7648308

Chen KC, Forsyth PS, Buchanan TM, Holmes KK. (1979). Amine content of vaginal fluid from untreated and treated patients with nonspecific vaginitis. J Clin Invest. 63: 828-835. https://doi.org/10.1172/JCI109382; PMid:447831 PMCid:PMC372023

Chen W, Luo Y, Yuan L, Xia Y, Nelson KE, Huang S et al. (2013). The restoration of the vaginal microbiota after treatment for bacterial vaginosis with metronidazole or probiotics. Microb Ecol. 65 (3): 773-780. https://doi.org/10.1007/s00248-012-0154-3; PMid:23250116

Chu DM, Seferovic M, Pace RM, Aagaard KM. (2018). The microbiome in preterm birth. Best Pract Res Clin Obstet Gynaecol. 52: 103-113. https://doi.org/10.1016/j.bpobgyn.2018.03.006; PMid:29753695

Eriksson K, Carlsson B, Forsum U, Larsson P‐G. (2005). A double‐blind treatment study of bacterial vaginosis with normal vaginal lactobacilli after an open treatment with vaginal clindamycin ovules. Acta Derm Venereol. 85: 42-46. https://doi.org/10.1080/00015550410022249; PMid:15848990

Gao H, Li X, Chen X, Hai D, Wei C, Zhang L, Li P. (2022). The Functional Roles of Lactobacillus acidophilus in Different Physiological and Pathological Processes. J. Microbiol. Biotechnol. 32: 1226-1233. https://doi.org/10.4014/jmb.2205.05041; PMid:36196014 PMCid:PMC9668099

Gaspar C, Donders GG, Palmeira-de-Oliveira R, Queiroz JA, Tomaz C, Martinez-de-Oliveira J, Palmeira-de-Oliveira A. (2018). Bacteriocin production of the probiotic Lactobacillus acidophilus KS400. AMB Express. 8 (1): 153. https://doi.org/10.1186/s13568-018-0679-z; PMid:30264211 PMCid:PMC6160374

Gillet E, Meys JFA, Verstraelen H et al. (2012). Association between bacterial vaginosis and cervical intraepithelial neoplasia: Systematic review and meta-analysis. Plos One. 7 (10): e45201. https://doi.org/10.1371/journal.pone.0045201; PMid:23056195 PMCid:PMC3462776

Giordani B, Melgoza LM, Parolin P, Foschi C, Marangoni A, Abruzzo A et al. (2018). Vaginal Bifidobacterium breve for preventing urogenital infections: Development of delayed release mucoadhesive oral tablets. Int J Pharm. 550 (1-2): 455-462. https://doi.org/10.1016/j.ijpharm.2018.09.003; PMid:30195082

Hallen A, Jarstrand C, Pahlson C. (1992). Treatment of bacterial vaginosis with lactobacilli. Sex Transm Dis. 19: 146-148. https://doi.org/10.1097/00007435-199205000-00007; PMid:1523530

Hall-Stoodley L, Stoodley P. (2009). Evolving concepts in biofilm infections. Cell Microbiol. 11 (7):1034-1043. https://doi.org/10.1111/j.1462-5822.2009.01323.x; PMid:19374653

Hearps AC, Tyssen D, Srbinovski D, Bayigga L, Diaz DJD, Aldunate M et al. (2017). Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition. Mucosal Immunol. 10 (6): 1480-1490. https://doi.org/10.1038/mi.2017.27; PMid:28401934

Hellinger R, Koehbach J, Fedchuk H, Sauer B, Huber R, Gruber C, Gründemanna C. (2014). Immunosuppressive activity of an aqueous Viola tricolor herbal extract. J Ethnopharmacol. 151 (1): 299-306. https://doi.org/10.1016/j.jep.2013.10.044; PMid:24216163 PMCid:PMC3918579

Hillier SL. (1995). Treatment of bacterial vaginosis. Female Patient. 5: 6-16.

Ibnou-Zekri N, Blum S, Schiffrin EJ, von der Weid T. (2003). Divergent Patterns of Colonization and Immune Response Elicited from Two Intestinal Lactobacillus Strains That Display Similar Properties In Vitro. Infect Immun. 71 (1): 428-436. https://doi.org/10.1128/IAI.71.1.428-436.2003; PMid:12496193 PMCid:PMC143181

Joseph RJ, Ser HL, Kuai YH, Tan LT, Arasoo V, Letchumanan V et al. (2021). Finding a Balance in the Vaginal Microbiome: How Do We Treat and Prevent the Occurrence of Bacterial Vaginosis? Antibiotics. 10 (6): 719. https://doi.org/10.3390/antibiotics10060719; PMid:34203908 PMCid:PMC8232816

Kroon SJ, Ravel J, Huston WM. (2018). Cervicovaginal microbiota, women's health, and reproductive outcomes. Fertil Steril. 110: 327-336. https://doi.org/10.1016/j.fertnstert.2018.06.036; PMid:30098679

Leitich H, Bodner-Adler B, Brunbauer M, Kaider A, Egarter C, Husslein P. (2003). Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis. Am J Obstet Gynecol 189 (1): 139-147. https://doi.org/10.1067/mob.2003.339; PMid:12861153

Machado A, Cerca N. (2015). Influence of biofilm formation by Gardnerella vaginalis and other anaerobes on bacterial vaginosis. J Infect Dis. 212 (12): 1856-1861. https://doi.org/10.1093/infdis/jiv338; PMid:26080369

Makella S, Madhivanan С. (2020). Bacterial vaginosis-A brief synopsis of the literature. Eur J Obstet Gynecol Reprod Biol. 245: 143-148. Epub 2019 Dec 24. https://doi.org/10.1016/j.ejogrb.2019.12.035; PMid:31901667 PMCid:PMC6989391

Mason MJ, Winter AJ. (2017). How to diagnose and treatbaerobic and desquamative inflammatory vaginitis. Sex Transm Infect. 93: 8-10. https://doi.org/10.1136/sextrans-2015-052406; PMid:27272705

Mastromarino P, Macchia S, Meggiorini L et al. (2009). Effectiveness of Lactobacillus-containing vaginal tablets in the treatment of symptomatic bacterial vaginosis. Clin Microbiol Infect. 15: 67-74. https://doi.org/10.1111/j.1469-0691.2008.02112.x; PMid:19046169

Meng B, Li G, Zeng Z, Zheng B, Xia Y, Li C et al. (2022). Establishment of early diagnosis models for cervical precancerous lesions using large-scale cervical cancer screening datasets. Virol J. 19 (1): 177. https://doi.org/10.1186/s12985-022-01908-w; PMid:36335385 PMCid:PMC9636682

Mitchell C, Manhart LE, Thomas K, Fiedler T, Fredricks DN, Marrazzo J. (2012). Behavioral predictors of colonization with Lactobacillus crispatus or Lactobacillus jensenii after treatment for bacterial vaginosis: a cohort study. Infect Dis Obstet Gynecol. Article ID: 706540. https://doi.org/10.1155/2012/706540; PMid:22693410 PMCid:PMC3369434

Mitchell CM, Anyalechi GE, Cohen CR, Haggerty C, Manhart L, Hillier S. (2021). Etiology and Diagnosis of Pelvic Inflammatory Disease: Looking Beyond Gonorrhea and Chlamydia. J Infect Dis. 12: 29-35. https://doi.org/10.1093/infdis/jiab067; PMid:34396407 PMCid:PMC8365120

Mitchell H. (2004). Vaginal discharge - causes, diagnosis, and treatment. BMJ. 328: 1306-1308. https://doi.org/10.1136/bmj.328.7451.1306; PMid:15166070 PMCid:PMC420177

Muñoz-Barreno A, Cabezas-Mera F, Tejera E, Machado A. (2021). Comparative Effectiveness of Treatments for Bacterial Vaginosis: A Network Meta-Analysis. Antibiotics. 10: 978. https://doi.org/10.3390/antibiotics10080978; PMid:34439028 PMCid:PMC8388924

Nagaraja P. (2005). Antibiotic resistance of Gardnerella vaginalis in recurrent bacterial vaginosis. Ind J of Med Microbiol. 26 (2): 155-157. https://doi.org/10.1016/S0255-0857(21)01933-2; PMid:18445953

Nikonyuk TR, Beniuk VO. (2007). Bacterial vaginosis. Contemporary approaches to diagnosis and treatment. News of medicine and pharmacy. 1: 205.

Oduyebo OO, Anorlu RI, Ogunsola FT. (2009). The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant women. Cochrane Database Syst. Rev. 3: CD006055. https://doi.org/10.1002/14651858.CD006055.pub2; PMid:19588379

Oduyebo OO, Anorlu RI, Ogunsola FT. (2009). The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant women. Cochrane Database Syst Rev. 3: CD006055. https://doi.org/10.1002/14651858.CD006055.pub2; PMid:19588379

Peebles K, Velloza J, Balkus E, McClelland R, Barnabas R. (2019). High Global Burden and Costs of Bacterial Vaginosis: A Systematic Review and Meta-Analysis. Sex Transm Dis. 46 (5): 304-311. https://doi.org/10.1097/OLQ.0000000000000972; PMid:30624309

Ravel J, Moreno I, Simón C. (2021). Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease. Am J Obstet Gynecol. 224 (3): 251-257 https://doi.org/10.1016/j.ajog.2020.10.019; PMid:33091407

Satterwhite CL, Torrone E, Meites E, Dunne EF, Mahajan R, Ocfemia MC et al. (2013). Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008. Sex Transm Dis. 40 (3): 187-193. https://doi.org/10.1097/OLQ.0b013e318286bb53; PMid:23403598

Shalev E, Battino S, Weiner E, Colodner R, Keness Y. (1996). Ingestion of yogurt containing Lactobacillus acidophilus compared with pasteurized yogurt as prophylaxis for recurrent candidal vaginitis and bacterial vaginosis. Arch Fam Med. 5 (5): 593-596. https://doi.org/10.1001/archfami.5.10.593; PMid:8930233

Sherrard J, Wilson J, Donders G et al. (2018). European (IUSTI/WHO) International Union against sexually transmitted infections (IUSTI) World Health Organisation (WHO) guideline on the management of vaginal discharge. International Journal of STD & AIDS. 29 (13): 1258-1272. https://doi.org/10.1177/0956462418785451; PMid:30049258

Sobel JD, Karpas Z, Lorber A. (2012). Diagnosing vaginal infections through measurement of biogenic amines by ion mobility spectrometry. Eur J Obstet Gynecol Reprod Biol. 163: 81-84. https://doi.org/10.1016/j.ejogrb.2012.03.022; PMid:22520996

Sobel JD, Schmitt C, Meriweather C. (1993). Long term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin. J Infect Dis. 167: 783-784. https://doi.org/10.1093/infdis/167.3.783; PMid:8440952

Spandorfer SD, Neuer A, Giraldo PC, Rosenwaks Z, Witkin SS. (2001). Relationship of abnormal vaginal flora, proinflammatory cytokines and idiopathic infertility in women undergoing IVF. J Reprod Med. 46: 806-810.

Swidsinski A, Doerffel Y, Loening-Baucke V et al. (2010). Gardnerella Biofilm involves Females and Males and is sexually transmitted. Gynecol Obstet Invest. 70: 256-263. https://doi.org/10.1159/000314015; PMid:21051845

Swidsinski A, Mendling W, Loening-Baucke V et al. (2005). Adherent biofilms in bacterial vaginosis. Obstet Gynecol. 106 (5); Part 1: 1013-1023. https://doi.org/10.1097/01.AOG.0000183594.45524.d2; PMid:16260520

Swidsinski A, Mendling W, Loening-Baucke V, Swidsinski S, Dörffel Y, Scholze J et al. (2008). An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am J Obstet Gynecol. 198 (1): 97.e1-6. https://doi.org/10.1016/j.ajog.2007.06.039; PMid:18005928

Tachedjian G, Aldunate M, Bradshaw CS, Cone RA. (2017). The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol. 168: 782-792. https://doi.org/10.1016/j.resmic.2017.04.001; PMid:28435139

Tan H, Fu Y, Yang C, Ma J. (2017). Effects of metronidazole combined probiotics over metronidazole alone for the treatment of bacterial vaginosis: a meta-analysis of randomized clinical trials. Arch Gynecol Obstet. 295 (6): 1331-1339. https://doi.org/10.1007/s00404-017-4366-0; PMid:28386675

Tatarchuk TF, Bulavenko OV, Bondarenko HM, Dubossarska ZM, Dubossarska YuO, Artyomenko VV et al. (2023). Abnormal vaginal discharge. Evidence-based clinical guideline on Ministry of Health of Ukraine SE "State Expert Center of the Ministry of Health of Ukraine" SI "Institute of Pediatrics, Obstetrics and Gynecology named after Academician O.M. Lukyanova of the National Academy of Sciences of Ukraine". URL: https://www.dec.gov.ua/wp-content/uploads/2023/01/knavv2022-2264.pdf.

Tatarchuk TF, Kalugina LV, Petrova GA, Radchenko VV et al. (2020). Vaginal discharge syndrome. Problem with many unknowns. Reproductive endocrinology. 3 (53): 102-108. https://doi.org/10.18370/2309-4117.2020.53.94-100

Van Oostrum N, De Sutter P, Meys J, Verstraelen H. (2013). Risks associated with bacterial vaginosis in infertility patients: a systematic review and meta-analysis. Hum Reprod. 28: 1809-1815. https://doi.org/10.1093/humrep/det096; PMid:23543384

Van Teijlingen NH, Helgers LC, Zijlstra-Willems EM et al. (2020). Vaginal dysbiosis associatedbacteria Megasphaera elsdenii and Prevotella timonensis induce immune activation via dendritic cells. J Reprod Immunol. 138: 103085. https://doi.org/10.1016/j.jri.2020.103085; PMid:32004804

Volkov TA, Bolshakova GM. (2009). Microflora of the vagina in women of reproductive age in normal conditions and with various pathologies. Annals of the Mechnikov Institute. 1: 5-13.

Watts H, Fazarri M, Minkoff H, Hillier SL, Sha B, Glesby M et al. (2005). Genital Infections on the Natural History of Human Papillomavirus Infection in HIV-1 - Infected and High-Risk HIV-1 Uninfected Women. J Infect Dis. 7: 1129-1139. https://doi.org/10.1086/427777; PMid:15747249

Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I et al. (2021). Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep. 70 (4): 1-187. https://doi.org/10.15585/mmwr.rr7004a1; PMid:34292926 PMCid:PMC8344968

Workowski KA, Bolan GA. (2015). Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines. MMWR Recomm. Rep. 64: 69-72.

Zhabchenko IA, Lishchenko IS. (2015). The effectiveness of the use of express tests in patients with premature and late pregnancy on the background of bacterial vaginosis. Medical aspects of a woman's health. 1 (87): 43-47.

Published

2023-09-28