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Molecular analysis of the relationship between specific vaginal bacteria and bacterial vaginosis metronidazole therapy failure

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Abstract

Bacterial vaginosis frequently persists, even after treatment. The role of some strains of bacteria associated with bacterial vaginosis treatment failure remains poorly defined. The aim of our study was to define the risk of bacterial vaginosis treatment failure, including pre-treatment detection of specific vaginal bacteria. Bacterial vaginosis is present when the Nugent score is ≥7 and the modified Amsel criteria is positive. Women with bacterial vaginosis were treated with intravaginal metronidazole gel nightly for 5 nights. The 454 pyrosequencing method was used to detect bacteria in vaginal fluid. By univariate analysis, a history of bacterial vaginosis, intrauterine device use and the presence of Facklamia, Corynebacterium and Veillonella were significantly associated with bacterial vaginosis treatment failure. Lactobacillus crispatus, Lactobacillus pentosus and Megasphaera were significantly associated with curing bacterial vaginosis. After logistic regression analysis and detection of these bacteria for test-of-cure, we found that women who had a history of bacterial vaginosis had a higher incidence of bacterial vaginosis treatment failure, whereas women with L. crispatus had a lower incidence of treatment failure. Post-treatment sexual activity was not associated with the treatment effect. Our data suggested that treatment failure may be not caused by drug resistance. Rather, it has a closer relationship with the failed restoration of lactobacilli.

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References

  1. Schwebke JR (2009) New concepts in the etiology of bacterial vaginosis. Curr Infect Dis Rep 11(2):143–147

    Article  PubMed  Google Scholar 

  2. Koumans EH, Sternberg M, Bruce C, McQuillan G, Kendrick J, Sutton M et al (2007) The prevalence of bacterial vaginosis in the United States, 2001–2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis 34(11):864–869

    Article  PubMed  Google Scholar 

  3. Fredricks DN, Fiedler TL, Marrazzo JM (2005) Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 353(18):1899–1911

    Article  PubMed  CAS  Google Scholar 

  4. Ling Z, Kong J, Liu F, Zhu H, Chen X, Wang Y et al (2010) Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis. BMC Genomics 11:488

    Article  PubMed  PubMed Central  Google Scholar 

  5. Schellenberg JJ, Card CM, Ball TB, Mungai JN, Irungu E, Kimani J et al (2012) Bacterial vaginosis, HIV serostatus and T-cell subset distribution in a cohort of East African commercial sex workers: retrospective analysis. AIDS 26(3):387–393

    Article  PubMed  Google Scholar 

  6. King CC, Jamieson DJ, Wiener J, Cu-Uvin S, Klein RS, Rompalo AM et al (2011) Bacterial vaginosis and the natural history of human papillomavirus. Infect Dis Obstet Gynecol 2011:319460

    Article  PubMed  PubMed Central  Google Scholar 

  7. Cohen CR, Lingappa JR, Baeten JM, Ngayo MO, Spiegel CA, Hong T et al (2012) Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples. PLoS Med 9(6):e1001251

    Article  PubMed  PubMed Central  Google Scholar 

  8. Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH et al (1995) Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group. N Engl J Med 333(26):1737–1742

    Article  PubMed  CAS  Google Scholar 

  9. Myer L, Denny L, Telerant R, Souza Md, Wright TC Jr, Kuhn L (2005) Bacterial vaginosis and susceptibility to HIV infection in South African women: a nested case–control study. J Infect Dis 192(8):1372–1380

    Article  PubMed  Google Scholar 

  10. Ness RB, Kip KE, Hillier SL, Soper DE, Stamm CA, Sweet RL et al (2005) A cluster analysis of bacterial vaginosis-associated microflora and pelvic inflammatory disease. Am J Epidemiol 162(6):585–590

    Article  PubMed  Google Scholar 

  11. Ferris DG, Litaker MS, Woodward L, Mathis D, Hendrich J (1995) Treatment of bacterial vaginosis: a comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. J Fam Pract 41(5):443–449

    PubMed  CAS  Google Scholar 

  12. Bunge KE, Beigi RH, Meyn LA, Hillier SL (2009) The efficacy of retreatment with the same medication for early treatment failure of bacterial vaginosis. Sex Transm Dis 36(11):711–713

    Article  PubMed  Google Scholar 

  13. Livengood CH 3rd, Soper DE, Sheehan KL, Fenner DE, Martens MG, Nelson AL et al (1999) Comparison of once-daily and twice-daily dosing of 0.75% metronidazole gel in the treatment of bacterial vaginosis. Sex Transm Dis 26(3):137–142

    Article  PubMed  Google Scholar 

  14. Fischbach F, Petersen EE, Weissenbacher ER, Martius J, Hosmann J, Mayer H (1993) Efficacy of clindamycin vaginal cream versus oral metronidazole in the treatment of bacterial vaginosis. Obstet Gynecol 82(3):405–410

    PubMed  CAS  Google Scholar 

  15. Bradshaw CS, Morton AN, Hocking J, Garland SM, Morris MB, Moss LM et al (2006) High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis 193(11):1478–1486

    Article  PubMed  Google Scholar 

  16. Klatt TE, Cole DC, Eastwood DC, Barnabei VM (2010) Factors associated with recurrent bacterial vaginosis. J Reprod Med 55(1–2):55–61

    PubMed  Google Scholar 

  17. Bradshaw CS, Morton AN, Hocking J, Garland SM, Morris MB, Moss LM et al (2006) High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis 193(11):1478–1486

    Article  PubMed  Google Scholar 

  18. Marrazzo JM, Thomas KK, Agnew K, Ringwood K (2010) Prevalence and risks for bacterial vaginosis in women who have sex with women. Sex Transm Dis 37(5):335–339

    PubMed  PubMed Central  Google Scholar 

  19. Bradshaw CS, Vodstrcil LA, Hocking JS, Law M, Pirotta M, Garland SM et al (2013) Recurrence of bacterial vaginosis is significantly associated with posttreatment sexual activities and hormonal contraceptive use. Clin Infect Dis 56(6):777–786

    Article  PubMed  CAS  Google Scholar 

  20. Fredricks DN, Fiedler TL, Thomas KK, Mitchell CM, Marrazzo JM (2009) Changes in vaginal bacterial concentrations with intravaginal metronidazole therapy for bacterial vaginosis as assessed by quantitative PCR. J Clin Microbiol 47(3):721–726

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Marrazzo JM, Thomas KK, Fiedler TL, Ringwood K, Fredricks DN (2008) Relationship of specific vaginal bacteria and bacterial vaginosis treatment failure in women who have sex with women. Ann Intern Med 149(1):20–28

    Article  PubMed  PubMed Central  Google Scholar 

  22. Nugent RP, Krohn MA, Hillier SL (1991) Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol 29(2):297–301

    PubMed  CAS  PubMed Central  Google Scholar 

  23. Marrazzo JM, Martin DH, Watts DH, Schulte J, Sobel JD, Hillier SL et al (2010) Bacterial vaginosis: identifying research gaps proceedings of a workshop sponsored by DHHS/NIH/NIAID. Sex Transm Dis 37(12):732–744

    Article  PubMed  PubMed Central  Google Scholar 

  24. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA et al (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature 437(7057):376–380

    PubMed  CAS  PubMed Central  Google Scholar 

  25. Hamady M, Walker JJ, Harris JK, Gold NJ, Knight R (2008) Error-correcting barcoded primers for pyrosequencing hundreds of samples in multiplex. Nat Methods 5(3):235–237

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Turovskiy Y, Sutyak Noll K, Chikindas ML (2011) The aetiology of bacterial vaginosis. J Appl Microbiol 110(5):1105–1128

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Pavlova SI, Kiliç AO, Mou SM, Tao L (1997) Phage infection in vaginal lactobacilli: an in vitro study. Infect Dis Obstet Gynecol 5(1):36–44

    PubMed  CAS  PubMed Central  Google Scholar 

  28. Pavlova SI, Tao L (2000) Induction of vaginal Lactobacillus phages by the cigarette smoke chemical benzo[a]pyrene diol epoxide. Mutat Res 466(1):57–62

    Article  PubMed  CAS  Google Scholar 

  29. Damelin LH, Paximadis M, Mavri-Damelin D, Birkhead M, Lewis DA, Tiemessen CT (2011) Identification of predominant culturable vaginal Lactobacillus species and associated bacteriophages from women with and without vaginal discharge syndrome in South Africa. J Med Microbiol 60(Pt 2):180–183

    Article  PubMed  Google Scholar 

  30. Hale LP, Swidsinski A, Mendling W (2006) Bacteria associated with bacterial vaginosis. N Engl J Med 354(2):202–203, author reply 202–203

    Article  PubMed  CAS  Google Scholar 

  31. 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(4):1124–1129

    Article  PubMed  Google Scholar 

  32. Meltzer MC, Desmond RA, Schwebke JR (2008) Association of mobiluncus curtisii with recurrence of bacterial vaginosis. Sex Transm Dis 35(6):611–613

    Article  PubMed  PubMed Central  Google Scholar 

  33. Nagaraja P (2008) Antibiotic resistance of Gardnerella vaginalis in recurrent bacterial vaginosis. Indian J Med Microbiol 26(2):155–157

    Article  PubMed  CAS  Google Scholar 

  34. Menard JP, Fenollar F, Raoult D, Boubli L, Bretelle F (2012) Self-collected vaginal swabs for the quantitative real-time polymerase chain reaction assay of Atopobium vaginae and Gardnerella vaginalis and the diagnosis of bacterial vaginosis. Eur J Clin Microbiol Infect Dis 31(4):513–518

    Article  PubMed  CAS  Google Scholar 

  35. 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.e1–97.e6

    Article  Google Scholar 

  36. Sobel JD, Ferris D, Schwebke J, Nyirjesy P, Wiesenfeld HC, Peipert J et al (2006) Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis. Am J Obstet Gynecol 194(5):1283–1289

    Article  PubMed  CAS  Google Scholar 

  37. Schwebke JR, Desmond RA (2007) A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis. Clin Infect Dis 44(2):213–219

    Article  PubMed  CAS  Google Scholar 

  38. Ness RB, Hillier SL, Richter HE, Soper DE, Stamm C, McGregor J et al (2002) Douching in relation to bacterial vaginosis, lactobacilli, and facultative bacteria in the vagina. Obstet Gynecol 100(4):765

    Article  PubMed  Google Scholar 

  39. Hassan WM, Lavreys L, Chohan V, Richardson BA, Mandaliya K, Ndinya-Achola JO et al (2007) Associations between intravaginal practices and bacterial vaginosis in Kenyan female sex workers without symptoms of vaginal infections. Sex Transm Dis 34(6):384–388

    PubMed  Google Scholar 

  40. Holzman C, Leventhal JM, Qiu H, Jones NM, Wang J; BV Study Group (2001) Factors linked to bacterial vaginosis in nonpregnant women. Am J Public Health 91(10):1664–1670

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  41. Madden T, Grentzer JM, Secura GM, Allsworth JE, Peipert JF (2012) Risk of bacterial vaginosis in users of the intrauterine device: a longitudinal study. Sex Transm Dis 39(3):217–222

    Article  PubMed  PubMed Central  Google Scholar 

  42. Sanchez S, Garcia PJ, Thomas KK, Catlin M, Holmes KK (2004) Intravaginal metronidazole gel versus metronidazole plus nystatin ovules for bacterial vaginosis: a randomized controlled trial. Am J Obstet Gynecol 191(6):1898–1906

    Article  PubMed  CAS  Google Scholar 

  43. Fethers KA, Fairley CK, Morton A, Hocking JS, Hopkins C, Kennedy LJ et al (2009) Early sexual experiences and risk factors for bacterial vaginosis. J Infect Dis 200(11):1662–1670

    Article  PubMed  Google Scholar 

  44. Fethers K, Twin J, Fairley CK, Fowkes FJ, Garland SM, Fehler G et al (2012) Bacterial vaginosis (BV) candidate bacteria: associations with BV and behavioural practices in sexually-experienced and inexperienced women. PLoS One 7(2):e30633

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  45. Evans AL, Scally AJ, Wellard SJ, Wilson JD (2007) Prevalence of bacterial vaginosis in lesbians and heterosexual women in a community setting. Sex Transm Infect 83(6):470–475

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was funded by a project supported by the National Natural Science Foundation of China: 81200411, 81170535. The funding sources had no role in the design and conduct of the study.

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The authors declare that they have no conflict of interest in relation to this article.

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Correspondence to Q. Liao.

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B. Wang and B.B. Xiao contributed equally to this study.

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Wang, B., Xiao, B.B., Shang, C.G. et al. Molecular analysis of the relationship between specific vaginal bacteria and bacterial vaginosis metronidazole therapy failure. Eur J Clin Microbiol Infect Dis 33, 1749–1756 (2014). https://doi.org/10.1007/s10096-014-2128-5

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