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Archives of Gynecology and Obstetrics

, Volume 295, Issue 6, pp 1331–1339 | Cite as

Effects of metronidazole combined probiotics over metronidazole alone for the treatment of bacterial vaginosis: a meta-analysis of randomized clinical trials

  • Hongying Tan
  • Yunque Fu
  • Chunlin Yang
  • Jianting MaEmail author
Review

Abstract

Object

To evaluate the curative effect of metronidazole combined probiotics over metronidazole alone in the treatment of BV.

Methods

We are searching randomized controlled trials on major online databases including PubMed, Science Direct, and Cochrane Database between 1990 and 2015. The primary outcome measure was the cure rate of BV. Cochran’s Chi-square test (Q test) was used to test for heterogeneity among trials, and the I 2 index. We used mixed-effects modeling for parameters of the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs).

Results

Analysis suggests the cure rate of BV [RR = 1.12, 95% CI (0.94–1.32), p = 0.20], and the I 2 index was 83%. The value of I 2 index decreased to 16% after removing the study of Anukam et al., and Amsel 1.04 (95% CI 0.96–1.13) (p = 0.35), Nugent 1.02 (95% CI 0.94–1.11), short-term 1.01 (95% CI 0.93–1.10) (p = 0.79), long-term 1.06 (95% CI 0.98–1.14) (p = 0.13), Europe 1.06 (95% CI 0.95–1.19) (p = 0.32), Non-Europe 0.99 (95% CI 0.94–1.05) (p = 0.83). When the two same groups data were combined, respectively, the RRs for all studies were the same as 1.03 (95% CI 0.96–1.09) (p = 0.42) showing that there is not statistically significant in relevant stratums.

Conclusion

The result has showed an overall little significance for the efficacy of metronidazole combined probiotics over metronidazole alone for the treatment of BV. We need more further studies to provide enough evidence to confirm the benefits of probiotics in the treatment of BV.

Keywords

Bacterial vaginosis Meta-analysis Probiotics Metronidazole 

Notes

Compliance with ethical standards

Conflict of interest

All authors declare no conflicts of interest. We have had full control of all primary data and we agree to allow the Journal to review their data if requested.

Author contributions

HT: Resources, Data Collection, Data analysis, Manuscript writing. YF: Data analysis, Manuscript writing. CY: Data analysis, Manuscript writing. JM: Resources, Manuscript writing, Supervision.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    Nelson DB, Macones G (2002) Bacterial vaginosis in pregnancy: current findings and future directions[J]. Epidemiol Rev 24 (2):102–108CrossRefPubMedGoogle Scholar
  2. 2.
    Cauci S, Driussi S, De SD et al (2002) Prevalence of bacterial vaginosis and vaginal flora changes in peri- and postmenopausal women[J]. J Clin Microbiol 40 (6):2147–2152CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Allsworth JE, Peipert JF (2007) Prevalence of bacterial vaginosis: 2001–2004 National Health and Nutrition Examination Survey data[J]. Obstetr Gynecol 109 (109):114–120CrossRefGoogle Scholar
  4. 4.
    Sobel JD (2000) Bacterial vaginosis[J]. Medicine (Baltimore) 71 (51):349–356Google Scholar
  5. 5.
    Mohanty S, Sood S, Kapil A et al (2010) Interobserver variation in the interpretation of Nugent scoring method for diagnosis of bacterial vaginosis[J]. Indian J Med Res 131 (1):88–91PubMedGoogle Scholar
  6. 6.
    Marrazzo JM, Cook RL, Wiesenfeld HC et al (2006) Women’s satisfaction with an intravaginal Lactobacillus capsule for the treatment of bacterial vaginosis[J]. J Womens Health 15 (9):1053–1060CrossRefGoogle Scholar
  7. 7.
    Leitich H, Bodner-Adler B, Brunbauer M et al (2003) Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis ☆[J]. Am J Obstetr Gynecol 189 (1):139–147CrossRefGoogle Scholar
  8. 8.
    Hoyme UB, Huebner J (2010) Prevention of preterm birth is possible by vaginal pH screening, early diagnosis of bacterial vaginosis or abnormal vaginal flora and treatment[J]. Gynecol Obstetr Investig 70 (4):286–290CrossRefGoogle Scholar
  9. 9.
    Guo YL, You K, Qiao J et al (2012) Bacterial vaginosis is conducive to the persistence of HPV infection[J]. Int J Std Aids 23 (8):581–584CrossRefPubMedGoogle Scholar
  10. 10.
    Gillet E, Meys JF, Verstraelen H et al (2011) Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: a meta-analysis[J]. BMC Infect Dis 11 (1):10CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Mcgregor JA, French JI, Jones W et al (1994) Bacterial vaginosis is associated with prematurity and vaginal fluid mucinase and sialidase: results of a controlled trial of topical clindamycin cream[J]. Am J Obstetr Gynecol 170 (4):1059–1060CrossRefGoogle Scholar
  12. 12.
    Amsel R, Totten PA, Spiegel CA et al (1969) Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations[J]. Am J Med 74 (1):14–22CrossRefGoogle Scholar
  13. 13.
    Nugent RP, Krohn MA, Hillier SL (1991) Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation[J]. J Clin Microbiol 29 (2):297–301PubMedPubMedCentralGoogle Scholar
  14. 14.
    Mclean NW, Rosenstein IJ (2000) Characterisation and selection of a Lactobacillus species to re-colonise the vagina of women with recurrent bacterial vaginosis[J]. J Med Microbiol 49 (6):543–552CrossRefPubMedGoogle Scholar
  15. 15.
    Sethi S, Das A, Sharma M (2006) Inhibition of Gardnerella vaginalis by lactobacilli[J]. Int J Gynaecol Obstetr 93 (2):158–159CrossRefGoogle Scholar
  16. 16.
    Joesoef M R, Schmid G P (1995) Bacterial vaginosis: review of treatment options and potential clinical indications for therapy[J]. Clin Infect Dis 20 (Supplement 1):S57CrossRefGoogle Scholar
  17. 17.
    Heczko PB, Tomusiak A, Adamski P et al (2015) Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vaginitis: a randomised, double-blind, placebo-controlled trial[J]. BMC Womens Health 15 (1):1–12CrossRefGoogle Scholar
  18. 18.
    Ozmen S, Turhan NO, Seckin NC (1998) Gardnerella-associated vaginitis: Comparison of three treatment modalities[J]. Turk J Med Sci 2:171–174Google Scholar
  19. 19.
    Marcone V, Calzolari E, Bertini M (2008) Effectiveness of vaginal administration of Lactobacillus rhamnosus following conventional metronidazole therapy: how to lower the rate of bacterial vaginosis recurrences[J]. New Microbiol 31 (3):429–433PubMedGoogle Scholar
  20. 20.
    Marcone V, Rocca G, Lichtner M et al (2010) Long-term vaginal administration of Lactobacillus rhamnosus as a complementary approach to management of bacterial vaginosis[J]. Int J Gynaecol Obstetr 110 (3):223–226CrossRefGoogle Scholar
  21. 21.
    Bradshaw CS, Marie P, Deborah DG et al (2012) Efficacy of oral metronidazole with vaginal clindamycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial[J]. PLoS One 7 (4):136–136CrossRefGoogle Scholar
  22. 22.
    Anukam K, Osazuwa E, Ahonkhai I et al (2006) Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial[J]. Microbes Infect 8 (6):1450–1454CrossRefPubMedGoogle Scholar
  23. 23.
    Myziuk L, Romanowski B, Johnson SC (2003) BVBlue test for diagnosis of bacterial vaginosis[J]. J Clin Microbiol 41 (5):1925–1928CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Blackwell AL, Phillips I, Fox AR et al (1984) Anaerobic vaginosis (non-specific vaginitis): clinical, microbiological, and therapeutic findings[J]. Lancet 2 (8364):1379–1382Google Scholar
  25. 25.
    Puapermpoonsiri S, Kato N, Watanabe K et al (1996) Vaginal microflora associated with bacterial vaginosis in japanese and thai pregnant women[J]. Clin Infect Dis 23 (4):748–752CrossRefPubMedGoogle Scholar
  26. 26.
    Smayevsky J, Canigia LF, Lanza A et al (2000) Vaginal microflora associated with bacterial vaginosis in nonpregnant women: reliability of sialidase detection[J]. Infect Dis Obstetr Gynecol 9 (1):17–22CrossRefGoogle Scholar
  27. 27.
    Marrazzo JM, Koutsky LA, Eschenbach DA et al (2002) Characterization of vaginal flora and bacterial vaginosis in women who have sex with women[J]. J Infect Dis 185 (9):1307–1313CrossRefPubMedGoogle Scholar
  28. 28.
    Ness RB, Hillier S, Richter HE et al (2003) Can known risk factors explain racial differences in the occurrence of bacterial vaginosis?[J]. J Natl Med Assoc 95 (3):201–212PubMedPubMedCentralGoogle Scholar
  29. 29.
    Brotman RM, Klebanoff MA, Nansel TR et al (2008) A longitudinal study of vaginal douching and bacterial vaginosis—a marginal structural modeling analysis[J]. Am J Epidemiol 168 (2):188–196CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Shu-Ning LI, Huang GL, Qun-Shan XU et al (2012) Analysis of vaginal secretion detection results of 13102 cases by combination of routine examination and BV 3-in -1 test[J]. Chin J Health Lab Technol 22(8):1880–1882Google Scholar
  31. 31.
    Senok AC, Verstraelen H, Temmerman M et al (2009) Probiotics for the treatment of bacterial vaginosis[J]. Cochrane Database Syst Rev 4:CD006289–CD006289Google Scholar
  32. 32.
    Reid G (2001) Probiotic agents to protect the urogenital tract against infection[J]. Am J Clin Nutr 73 (73):437S–443SPubMedGoogle Scholar
  33. 33.
    Fuller R (1989) Probiotics in man and animals[J]. J Appl Bacteriol 66 (5):365–378CrossRefPubMedGoogle Scholar
  34. 34.
    Reid G, Jass J, Sebulsky MT et al (2003) Potential uses of probiotics in clinical practice[J]. Clin Microbiol Rev 16 (4):658–672CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Lee JE, Lee S, Lee H et al (2013) Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort[J]. PLoS One 8 (5):e63514–e63514CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Hg K, Nr K, Mg G et al (2008) Lipoteichoic acid isolated from Lactobacillus plantarum inhibits lipopolysaccharide-induced TNF-alpha production in THP-1 cells and endotoxin shock in mice[J]. J Immunol 180 (4):2553–2561CrossRefGoogle Scholar
  37. 37.
    Kaji R, Kiyoshimashibata J, Nagaoka M et al (2010) Bacterial teichoic acids reverse predominant IL-12 production induced by certain Lactobacillus strains into predominant IL-10 production via TLR2-dependent ERK activation in macrophages[J]. J Immunol 184 (7):3505–3513CrossRefPubMedGoogle Scholar
  38. 38.
    Mcmillan A, Dell M, Zellar MP et al (2011) Disruption of urogenital biofilms by lactobacilli[J]. Colloids Surf B Biointerfaces 86 (1):58–64CrossRefPubMedGoogle Scholar
  39. 39.
    Gardiner GE, Heinemann C, Bruce AW et al (2002) Persistence of Lactobacillus fermentum RC-14 and Lactobacillus rhamnosus GR-1 but not L. rhamnosus GG in the human vagina as demonstrated by randomly amplified polymorphic DNA[J]. Clin Diagn Lab Immunol 9 (1):92–96PubMedPubMedCentralGoogle Scholar
  40. 40.
    Hughes VL, Hillier SL (1990) Microbiologic characteristics of Lactobacillus products used for colonization of the vagina[J]. Obstetr Gynecol 75 (2):244–248Google Scholar
  41. 41.
    Påhlson C, Larsson PG (1991) The ecologically wrong vaginal lactobacilli[J]. Med Hypotheses 36 (2):126–130CrossRefPubMedGoogle Scholar
  42. 42.
    Shen DS (2012) Microecology, bacterial vaginosis and probiotics[J]. Chin J Microecol 24 (6):570–572Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Hongying Tan
    • 1
  • Yunque Fu
    • 2
  • Chunlin Yang
    • 2
  • Jianting Ma
    • 2
    Email author
  1. 1.Medical School of Ningbo UniversityNingboChina
  2. 2.Department of Obstetrics and GynecologyThe Affiliated Yangming Hospital of Ningbo UniversityYuyaoChina

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