Making inroads into improving treatment of bacterial vaginosis - striving for long-term cure

Catriona S Bradshaw, Rebecca M Brotman, Catriona S Bradshaw, Rebecca M Brotman

Abstract

Bacterial vaginosis (BV) is one of the great enigmas in women's health, a common condition of unknown aetiology, which is associated with significant morbidity and unacceptably high recurrence rates. While it remains unclear whether BV recurrence is predominantly due to failure of current antibiotic regimens to eradicate BV-associated bacteria (BVAB) and biofilm, a failure of some women to re-establish a resilient Lactobacillus-dominant vaginal microbiota, reinfection from sexual partners, or a combination of these factors, it is inherently challenging to make significant inroads towards this goal. In this review, we will outline why BV is such a clinical and epidemiologic conundrum, and focus on several key approaches that we believe merit discussion and clinical research, including strategies to: i) prevent reinfection (partner treatment trials), ii) boost favourable vaginal Lactobacillus species and promote a Lactobacillus-dominant vaginal microbiome (hormonal contraceptive and probiotic trials) and iii) disrupt vaginal BV-associated biofilm.

Figures

Fig. 1
Fig. 1
BV recurrence and potential therapeutic strategies
Fig. 2
Fig. 2
Heatmap showing the distribution of bacterial taxa found in the vaginal microbial communities of 394 reproductive-age women in the U.S. Adapted with permission from Proceedings of the National Academy of Sciences of the United States of America [70]
Fig. 3
Fig. 3
Daily temporal dynamics of vaginal bacterial communities in six women over a 10-week period. The relative abundance of each bacterial taxa is depicted as interpolated bar graphs. The bacterial taxa are indicated on the right of each bar graph with color codes. Daily Nugent Gram stain scores (range 0–10) and pH (range 4–7) are indicated below the graph. Red solid circles represent menstruation. Missing pH values are indicated by red box, otherwise pH is in line with a value of 4. Missing Nugent scores are also indicated by the red box, otherwise the score is in line with 0. The figure illustrates that the top four participants (a, b, c, d) carry highly stable communities dominated by L. crispatus (a), L. iners (b) and non-Lactobacillus dominated communities (c and d). Women e and f experienced unstable communities with both high Nugent scores and pH. Adapted with permission from Microbiome [78]
Fig. 4
Fig. 4
Meta-analysis of hormonal contraception and prevalent BV. Figure first published in PLoS One [93]
Fig. 5
Fig. 5
Meta-analysis of hormonal contraception and incident BV. Figure first published in PLoS One [93]

References

    1. Bradshaw CS, Walker J, Fairley CK, Chen MY, Tabrizi SN, Donovan B, et al. Prevalent and incident bacterial vaginosis are associated with sexual and contraceptive behaviours in young Australian women. PLoS One. 2013;8(3):e57688. doi: 10.1371/journal.pone.0057688.
    1. Koumans EH, Sternberg M, Bruce C, McQuillan G, Kendrick J, Sutton M, et al. The prevalence of bacterial vaginosis in the United States, 2001–2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis. 2007;34(11):864–9. doi: 10.1097/OLQ.0b013e318074e565.
    1. Allsworth JE. Bacterial vaginosis--race and sexual transmission: issues of causation. Sex Transm Dis. 2010;37(3):137–9. doi: 10.1097/OLQ.0b013e3181d36bdc.
    1. Chico RM, Mayaud P, Ariti C, Mabey D, Ronsmans C, Chandramohan D. Prevalence of malaria and sexually transmitted and reproductive tract infections in pregnancy in sub-Saharan Africa: a systematic review. JAMA. 2012;307(19):2079–86. doi: 10.1001/jama.2012.3428.
    1. Koumans EH, Markowitz LE, Hogan V. Indications for therapy and treatment recommendations for bacterial vaginosis in nonpregnant and pregnant women: a synthesis of data. Clin Infect Dis. 2002;35(Suppl 2):S152–72. doi: 10.1086/342103.
    1. Brotman RM, Klebanoff MA, Nansel TR, Yu KF, Andrews WW, Zhang J, et al. Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection. J Infect Dis. 2010;202(12):1907–15. doi: 10.1086/657320.
    1. Peipert JF, Lapane KL, Allsworth JE, Redding CA, Blume JD, Stein MD. Bacterial vaginosis, race, and sexually transmitted infections: does race modify the association? Sex Transm Dis. 2008;35(4):363–7. doi: 10.1097/OLQ.0b013e31815e4179.
    1. Martin H, Richardson B, Nyange P, Lavreys L, Hillier S, Chohan B, et al. Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis. 1999;180:1863–8. doi: 10.1086/315127.
    1. Myer L, Kuhn L, Stein ZA, Wright TC, Jr, Denny L. Intravaginal practices, bacterial vaginosis, and women’s susceptibility to HIV infection: epidemiological evidence and biological mechanisms. Lancet Infect Dis. 2005;5(12):786–94. doi: 10.1016/S1473-3099(05)70298-X.
    1. Cherpes T, Meyn L, Krohn M, Lurie J, Hillier S. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Infect Dis. 2003;37:319–25. doi: 10.1086/375819.
    1. Martin DH. The microbiota of the vagina and its influence on women’s health and disease. Am J Med Sci. 2012;343:2–9. doi: 10.1097/MAJ.0b013e31823ea228.
    1. Cohen CR, Lingappa JR, Baeten JM, Ngayo MO, Spiegel CA, Hong T, et al. Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples. PLoS Med. 2012;9(6):e1001251. doi: 10.1371/journal.pmed.1001251.
    1. Bilardi JE, Walker S, Temple-Smith M, McNair R, Mooney-Somers J, Bellhouse C, et al. The burden of bacterial vaginosis: women’s experience of the physical, emotional, sexual and social impact of living with recurrent bacterial vaginosis. PLoS One. 2013;8(9):e74378. doi: 10.1371/journal.pone.0074378.
    1. Fredricks DN, Marrazzo JM. Molecular methodology in determining vaginal flora in health and disease: its time has come. Curr Infect Dis Rep. 2005;7(6):463–70. doi: 10.1007/s11908-005-0049-2.
    1. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med. 2005;353(18):1899–911. doi: 10.1056/NEJMoa043802.
    1. Fredricks DN, Fiedler TL, Thomas KK, Oakley BB, Marrazzo JM. Targeted PCR for detection of vaginal bacteria associated with bacterial vaginosis. J Clin Microbiol. 2007;45(10):3270–6. doi: 10.1128/JCM.01272-07.
    1. Boskey ER, Cone RA, Whaley KJ, Moench TR. Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. Hum Reprod. 2001;16(9):1809–13. doi: 10.1093/humrep/16.9.1809.
    1. Aroutcheva A, Gariti D, Simon M, Shott S, Faro J, Simoes JA, et al. Defense factors of vaginal lactobacilli. Am J Obstet Gynecol. 2001;185(2):375–9. doi: 10.1067/mob.2001.115867.
    1. Donia MS, Cimermancic P, Schulze CJ, Wieland Brown LC, Martin J, Mitreva M, et al. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell. 2014;158(6):1402–14. doi: 10.1016/j.cell.2014.08.032.
    1. Aldunate M, Tyssen D, Johnson A, Zakir T, Sonza S, Moench T, et al. Vaginal concentrations of lactic acid potently inactivate HIV. J Antimicrob Chemother. 2013;68(9):2015–25. doi: 10.1093/jac/dkt156.
    1. O’Hanlon DE, Moench TR, Cone RA. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect Dis. 2011;11(1):200. doi: 10.1186/1471-2334-11-200.
    1. Witkin SS, Alvi S, Bongiovanni AM, Linhares IM, Ledger WJ. Lactic acid stimulates interleukin-23 production by peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide. FEMS Immunol Med Microbiol. 2011;61(2):153–8. doi: 10.1111/j.1574-695X.2010.00757.x.
    1. Phukan N, Parsamand T, Brooks AE, Nguyen TN, Simoes-Barbosa A. The adherence of Trichomonas vaginalis to host ectocervical cells is influenced by lactobacilli. Sex Transm Infect. 2013;89(6):455–9. doi: 10.1136/sextrans-2013-051039.
    1. Macklaim JM, Gloor GB, Anukam KC, Cribby S, Reid G. At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4688–95. doi: 10.1073/pnas.1000086107.
    1. McMillan A, Macklaim JM, Burton JP, Reid G. Adhesion of lactobacillus iners AB-1 to human fibronectin: a key mediator for persistence in the vagina? Reprod Sci. 2013;20(7):791–6. doi: 10.1177/1933719112466306.
    1. Verstraelen H, Verhelst R, Claeys G, De Backer E, Temmerman M, Vaneechoutte M. Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and/or L. iners are more conducive to the occurrence of abnormal vaginal microflora. BMC Microbiol. 2009;9:116. doi: 10.1186/1471-2180-9-116.
    1. Witkin SS, Mendes-Soares H, Linhares IM, Jayaram A, Ledger WJ, Forney LJ. Influence of vaginal bacteria and D- and L-lactic acid isomers on vaginal extracellular matrix metalloproteinase inducer: implications for protection against upper genital tract infections. MBio. 2013;4(4):e00460–13. doi: 10.1128/mBio.00460-13.
    1. Fredricks DN. Molecular methods to describe the spectrum and dynamics of the vaginal microbiota. Anaerobe. 2011;17(4):191–5. doi: 10.1016/j.anaerobe.2011.01.001.
    1. Zozaya-Hinchliffe M, Lillis R, Martin DH, Ferris MJ. Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis. J Clin Microbiol. 2010;48(5):1812–9. doi: 10.1128/JCM.00851-09.
    1. Swidsinski A, Mendling W, Loening-Baucke V, Ladhoff A, Swidsinski S, Hale LP, et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol. 2005;106(5 Pt 1):1013–23. doi: 10.1097/01.AOG.0000183594.45524.d2.
    1. Swidsinski A, Mendling W, Loening-Baucke V, Swidsinski S, Dorffel Y, Scholze J, et al. An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am J Obstet Gynecol. 2008;198(1):97.e1–6. doi: 10.1016/j.ajog.2007.06.039.
    1. Averette HE, Weinstein GD, Frost P. Autoradiographic analysis of cell proliferation kinetics in human genital tissues. I. Normal cervix and vagina. Am J Obstet Gynecol. 1970;108(1):8–17. doi: 10.1016/0002-9378(70)90195-X.
    1. Yildirim S, Yeoman CJ, Janga SC, Thomas SM, Ho M, Leigh SR, et al. Primate vaginal microbiomes exhibit species specificity without universal Lactobacillus dominance. ISME J. 2014;8(12):2431–44. doi: 10.1038/ismej.2014.90.
    1. Neuendorf E, Gajer P, Bowlin AK, Marques PX, Ma B, Yang H, et al. Chlamydia caviae infection alters abundance but not composition of the guinea pig vaginal microbiota. Pathog Dis. 2015;73(4):ftv019. doi: 10.1093/femspd/ftv019.
    1. Noguchi K, Tsukumi K, Urano T. Qualitative and quantitative differences in normal vaginal flora of conventionally reared mice, rats, hamsters, rabbits, and dogs. Comp Med. 2003;53(4):404–12.
    1. Rivera AJ, Frank JA, Stumpf R, Salyers AA, Wilson BA, Olsen GJ, et al. Differences between the normal vaginal bacterial community of baboons and that of humans. Am J Primatol. 2011;73(2):119–26. doi: 10.1002/ajp.20851.
    1. Stumpf RM, Wilson BA, Rivera A, Yildirim S, Yeoman CJ, Polk JD, et al. The primate vaginal microbiome: comparative context and implications for human health and disease. Am J Phys Anthropol. 2013;152(Suppl 57):119–34. doi: 10.1002/ajpa.22395.
    1. Oduyebo OO, Anorlu RI, Ogunsola FT. The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant women. Cochrane Database Syst Rev. 2009;3:CD006055.
    1. Sobel JD, Schmitt C, Meriwether C. Long-term follow-up of patients with bacterial vaginosis treated with oral metronidazole and topical clindamycin. J Infect Dis. 1993;167(3):783–4. doi: 10.1093/infdis/167.3.783.
    1. Bradshaw CS, Morton AN, Hocking J, Garland SM, Morris MB, Moss LM, et al. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis. 2006;193(11):1478–86. doi: 10.1086/503780.
    1. Marrazzo JM, Thomas KK, Fiedler TL, Ringwood K, Fredricks DN. Relationship of specific vaginal bacteria and bacterial vaginosis treatment failure in women who have sex with women. Ann Intern Med. 2008;149(1):20–8. doi: 10.7326/0003-4819-149-1-200807010-00006.
    1. Sobel JD, Ferris D, Schwebke J, Nyirjesy P, Wiesenfeld HC, Peipert J, et al. Suppressive antibacterial therapy with 0.75 % metronidazole vaginal gel to prevent recurrent bacterial vaginosis. Am J Obstet Gynecol. 2006;194(5):1283–9. doi: 10.1016/j.ajog.2005.11.041.
    1. Taha TE, Kumwenda NI, Kafulafula G, Makanani B, Nkhoma C, Chen S, et al. Intermittent intravaginal antibiotic treatment of bacterial vaginosis in HIV-uninfected and -infected women: a randomized clinical trial. PLoS Clin Trials. 2007;2(2):e10. doi: 10.1371/journal.pctr.0020010.
    1. Hawes SE, Hillier SL, Benedetti J, Stevens CE, Koutsky LA, Wolner-Hanssen P, et al. Hydrogen peroxide-producing lactobacilli and acquisition of vaginal infections. J Infect Dis. 1996;174(5):1058–63. doi: 10.1093/infdis/174.5.1058.
    1. Fethers KA, Fairley CK, Hocking JS, Gurrin LC, Bradshaw CS. Sexual risk factors and bacterial vaginosis: a systematic review and meta-analysis. Clin Infect Dis. 2008;47(11):1426–35. doi: 10.1086/592974.
    1. Fethers KA, Fairley CK, Morton A, Hocking JS, Hopkins C, Kennedy LJ, et al. Early sexual experiences and risk factors for bacterial vaginosis. J Infect Dis. 2009;200(11):1662–70. doi: 10.1086/648092.
    1. Bump RC, Buesching WJ., III Bacterial vaginosis in virginal and sexually active adolescent females: evidence against exclusive sexual transmission. Am J Obstet Gynecol. 1988;158(4):935–9. doi: 10.1016/0002-9378(88)90097-X.
    1. Yen S, Shafer MA, Moncada J, Campbell CJ, Flinn SD, Boyer CB. Bacterial vaginosis in sexually experienced and non-sexually experienced young women entering the military. Obstet Gynecol. 2003;102(5 Pt 1):927–33. doi: 10.1016/S0029-7844(03)00858-5.
    1. Potter J. Should sexual partners of women with bacterial vaginosis receive treatment? Br J Gen Pract. 1999;49(448):913–8.
    1. Mehta SD. Systematic review of randomized trials of treatment of male sexual partners for improved bacterial vaginosis outcomes in women. Sex Transm Dis. 2012;39(10):822–30. doi: 10.1097/OLQ.0b013e3182631d89.
    1. Bradshaw CS, Vodstrcil LA, Hocking JS, Law M, Pirotta M, Garland SM, et al. Recurrence of bacterial vaginosis is significantly associated with post treatment sexual activities and hormonal contraceptive use. Clin Infect Dis. 2013;56(6):777–86. doi: 10.1093/cid/cis1030.
    1. Sanchez S, Garcia PJ, Thomas KK, Catlin M, Holmes KK. Intravaginal metronidazole gel versus metronidazole plus nystatin ovules for bacterial vaginosis: a randomized controlled trial. Am J Obstet Gynecol. 2004;191(6):1898–906. doi: 10.1016/j.ajog.2004.06.089.
    1. Schwebke JR, Desmond RA. A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis. Clin Infect Dis. 2007;44(2):213–9. doi: 10.1086/509577.
    1. Schwebke JR, Muzny CA, Josey WE. Role of Gardnerella vaginalis in the pathogenesis of bacterial vaginosis: a conceptual model. J Infect Dis. 2014;210(3):338–43. doi: 10.1093/infdis/jiu089.
    1. Bradshaw CS, Tabrizi SN, Read TRH, Garland SM, Hopkins CA, Moss LM, et al. Etiologies of non-gonococcal urethritis: bacteria, viruses and the association with oro-genital exposure. J Infect Dis. 2006;193:336–45. doi: 10.1086/499434.
    1. Piot P. Distribution of eight serotypes of Ureaplasma urealyticum in cases of non-gonococcal urethritis and of gonorrhoea, and in healthy persons. Br J Vener Dis. 1976;52(4):266–8.
    1. Schwebke JR, Rivers C, Lee J. Prevalence of Gardnerella vaginalis in male sexual partners of women with and without bacterial vaginosis. Sex Transm Dis. 2009;36(2):92–4. doi: 10.1097/OLQ.0b013e3181886727.
    1. Nelson DE, Dong Q, Van der Pol B, Toh E, Fan B, Katz BP, et al. Bacterial communities of the coronal sulcus and distal urethra of adolescent males. PLoS One. 2012;7(5):e36298. doi: 10.1371/journal.pone.0036298.
    1. Price LB, Liu CM, Johnson KE, Aziz M, Lau MK, Bowers J, et al. The effects of circumcision on the penis microbiome. PLoS One. 2010;5(1):e8422. doi: 10.1371/journal.pone.0008422.
    1. Gray RH, Wawer MJ, Serwadda D, Kigozi G. The role of male circumcision in the prevention of human papillomavirus and HIV infection. J Infect Dis. 2009;199(1):1–3. doi: 10.1086/595568.
    1. Swidsinski A, Loening-Baucke V, Mendling W, Dorffel Y, Schilling J, Halwani Z, et al. Infection through structured polymicrobial Gardnerella biofilms (StPM-GB) Histol Histopathol. 2014;29(5):567–87.
    1. Berger BJ, Kolton S, Zenilman JM, Cummings MC, Feldman J, McCormack WM. Bacterial vaginosis in lesbians: a sexually transmitted disease. Clin Infect Dis. 1995;21(6):1402–5. doi: 10.1093/clinids/21.6.1402.
    1. Marrazzo JM, Koutsky LA, Eschenbach DA, Agnew K, Stine K, Hillier SL. Characterization of vaginal flora and bacterial vaginosis in women who have sex with women. J Infect Dis. 2002;185(9):1307–13. doi: 10.1086/339884.
    1. Bailey JV, Farquhar C, Owen C. Bacterial vaginosis in lesbians and bisexual women. Sex Transm Dis. 2004;31(11):691–4. doi: 10.1097/01.olq.0000143093.70899.68.
    1. Evans AL, Scally AJ, Wellard SJ, Wilson JD. Prevalence of bacterial vaginosis in lesbians and heterosexual women in a community setting. Sex Transm Infect. 2007;83(6):470–5. doi: 10.1136/sti.2006.022277.
    1. Bradshaw CS, Walker SM, Vodstrcil LA, Bilardi JE, Law M, Hocking JS, et al. The influence of behaviors and relationships on the vaginal microbiota of women and their female partners: the WOW Health Study. J Infect Dis. 2014;209(10):1562–72. doi: 10.1093/infdis/jit664.
    1. Marrazzo JM, Thomas KK, Fiedler TL, Ringwood K, Fredricks DN. Risks for acquisition of bacterial vaginosis among women who report sex with women: a cohort study. PLoS One. 2010;5(6):e11139. doi: 10.1371/journal.pone.0011139.
    1. Vodstrcil LA, Walker SM, Hocking JS, Law M, Forcey DS, Fehler G, et al. Incident bacterial vaginosis (BV) in women who have sex with women is associated with behaviors that suggest sexual transmission of BV. Clin Infect Dis. 2015;60(7):1042–53.
    1. Marrazzo JM, Antonio M, Agnew K, Hillier SL. Distribution of genital Lactobacillus strains shared by female sex partners. J Infect Dis. 2009;199(5):680–3. doi: 10.1086/596632.
    1. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4680–7. doi: 10.1073/pnas.1002611107.
    1. Zhou X, Hansmann MA, Davis CC, Suzuki H, Brown CJ, Schütte U, et al. The vaginal bacterial communities of Japanese women resemble those of women in other racial groups. FEMS Immunol Med Microbiol. 2010;58(2):169–81. doi: 10.1111/j.1574-695X.2009.00618.x.
    1. Zhou X, Brown CJ, Abdo Z, Davis CC, Hansmann MA, Joyce P, et al. Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women. ISME J. 2007;1(2):121–33. doi: 10.1038/ismej.2007.12.
    1. Fredricks DN, Fiedler TL, Thomas KK, Mitchell CM, Marrazzo JM. Changes in vaginal bacterial concentrations with intravaginal metronidazole therapy for bacterial vaginosis as assessed by quantitative PCR. J Clin Microbiol. 2009;47(3):721–6. doi: 10.1128/JCM.01384-08.
    1. Martin DH, Zozaya M, Lillis RA, Myers L, Nsuami MJ, Ferris MJ. Unique vaginal microbiota that includes an unknown Mycoplasma-like organism is associated with Trichomonas vaginalis infection. J Infect Dis. 2013;207(12):1922–31. doi: 10.1093/infdis/jit100.
    1. Benning L, Golub ET, Anastos K, French AL, Cohen M, Gilbert D, et al. Comparison of lower genital tract microbiota in HIV-infected and uninfected women from Rwanda and the US. PLoS One. 2014;9(5):e96844. doi: 10.1371/journal.pone.0096844.
    1. Chaban B, Links MG, Jayaprakash TP, Wagner EC, Bourque DK, Lohn Z, et al. Characterization of the vaginal microbiota of healthy Canadian women through the menstrual cycle. Microbiome. 2014;2:23. doi: 10.1186/2049-2618-2-23.
    1. Gajer P, Brotman RM, Bai G, Sakamoto J, Schutte UM, Zhong X, et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med. 2012;4(132):132ra152. doi: 10.1126/scitranslmed.3003605.
    1. Ravel J, Brotman RM, Gajer P, Ma B, Nandy M, Fadrosh DW, et al. Daily temporal dynamics of vaginal microbiota before, during and after episodes of bacterial vaginosis. Microbiome. 2013;1(1):29. doi: 10.1186/2049-2618-1-29.
    1. Srinivasan S, Liu C, Mitchell CM, Fiedler TL, Thomas KK, Agnew KJ, et al. Temporal variability of human vaginal bacteria and relationship with bacterial vaginosis. PLoS One. 2010;5(4):e10197. doi: 10.1371/journal.pone.0010197.
    1. Senok AC, Verstraelen H, Temmerman M, Botta GA. Probiotics for the treatment of bacterial vaginosis. Cochrane Database Syst Rev. 2009;4:CD006289.
    1. Mastromarino P, Macchia S, Meggiorini L, Trinchieri V, Mosca L, Perluigi M, et al. Effectiveness of Lactobacillus-containing vaginal tablets in the treatment of symptomatic bacterial vaginosis. Clin Microbiol Infect. 2009;15(1):67–74. doi: 10.1111/j.1469-0691.2008.02112.x.
    1. Hemmerling A, Harrison W, Schroeder A, Park J, Korn A, Shiboski S, et al. Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis. Sex Transm Dis. 2010;37(12):745–50. doi: 10.1097/OLQ.0b013e3181e50026.
    1. Antonio MA, Meyn LA, Murray PJ, Busse B, Hillier SL. Vaginal colonization by probiotic Lactobacillus crispatus CTV-05 is decreased by sexual activity and endogenous Lactobacilli. J Infect Dis. 2009;199(10):1506–13. doi: 10.1086/598686.
    1. Ngugi BM, Hemmerling A, Bukusi EA, Kikuvi G, Gikunju J, Shiboski S, et al. Effects of bacterial vaginosis-associated bacteria and sexual intercourse on vaginal colonization with the probiotic lactobacillus crispatus CTV-05. Sex Transm Dis. 2011;38(11):1020–7. doi: 10.1097/OLQ.0b013e3182267ac4.
    1. Hemalatha R, Mastromarino P, Ramalaxmi BA, Balakrishna NV, Sesikeran B. Effectiveness of vaginal tablets containing lactobacilli versus pH tablets on vaginal health and inflammatory cytokines: a randomized, double-blind study. Eur J Clin Microbiol Infect Dis. 2012;31(11):3097–105. doi: 10.1007/s10096-012-1671-1.
    1. Reid G, Charbonneau D, Erb J, Kochanowski B, Beuerman D, Poehner R, et al. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol. 2003;35(2):131–4. doi: 10.1016/S0928-8244(02)00465-0.
    1. Martinez R, Franceschini S, Patta M. Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial. Can J Microbiol. 2009;55(2):133–8. doi: 10.1139/W08-102.
    1. Workowski KA, Berman S, Centers for Disease Control and Prevention Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59(RR-12):1–110.
    1. Riggs M, Klebanoff M, Nansel T, Zhang J, Schwebke J, Andrews W. Longitudinal association between hormonal contraceptives and bacterial vaginosis in women of reproductive age. Sex Transm Dis. 2007;34(12):954–9.
    1. Shoubnikova M, Hellberg D, Nilsson S, Mardh PA. Contraceptive use in women with bacterial vaginosis. Contraception. 1997;55(6):355–8. doi: 10.1016/S0010-7824(97)00044-9.
    1. Rifkin SB, Smith MR, Brotman RM, Gindi RM, Erbelding EJ. Hormonal contraception and risk of bacterial vaginosis diagnosis in an observational study of women attending STD clinics in Baltimore, MD. Contraception. 2009;80(1):63–7. doi: 10.1016/j.contraception.2009.01.008.
    1. Baeten JM, Nyange PM, Richardson BA, Lavreys L, Chohan B, Martin HL, Jr, et al. Hormonal contraception and risk of sexually transmitted disease acquisition: results from a prospective study. Am J Obstet Gynecol. 2001;185(2):380–5. doi: 10.1067/mob.2001.115862.
    1. Vodstrcil LA, Hocking JS, Law M, Walker S, Tabrizi SN, Fairley CK, et al. Hormonal contraception is associated with a reduced risk of bacterial vaginosis: a systematic review and meta-analysis. PLoS One. 2013;8(9):e73055. doi: 10.1371/journal.pone.0073055.
    1. De Seta F, Restaino S, De Santo D, Stabile G, Banco R, Busetti M, et al. Effects of hormonal contraception on vaginal flora. Contraception. 2012;86(5):526–9. doi: 10.1016/j.contraception.2012.02.012.
    1. Veres S, Miller L, Burington B. A comparison between the vaginal ring and oral contraceptives. Obstet Gynecol. 2004;104(3):555–63. doi: 10.1097/01.AOG.0000136082.59644.13.
    1. Calzolari E, Masciangelo R, Milite V, Verteramo R. Bacterial vaginosis and contraceptive methods. Int J Gynaecol Obstet. 2000;70(3):341–6. doi: 10.1016/S0020-7292(00)00217-4.
    1. Madden T, Grentzer JM, Secura GM, Allsworth JE, Peipert JF. Risk of bacterial vaginosis in users of the intrauterine device. Sex Transm Dis. 2012;39(3):217–22. doi: 10.1097/OLQ.0b013e31823e68fe.
    1. Jacobson JC, Turok DK, Dermish AI, Nygaard IE, Settles ML. Vaginal microbiome changes with levonorgestrel intrauterine system placement. Contraception. 2014;90(2):130–5. doi: 10.1016/j.contraception.2014.04.006.
    1. Spear GT, French AL, Gilbert D, Zariffard MR, Mirmonsef P, Sullivan TH, et al. Human alpha-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus. J Infect Dis. 2014;210(7):1019–28. doi: 10.1093/infdis/jiu231.
    1. Eschenbach DA, Thwin SS, Patton DL, Hooton TM, Stapleton AE, Agnew K, et al. Influence of the normal menstrual cycle on vaginal tissue, discharge, and microflora. Clin Infect Dis. 2000;30(6):901–7. doi: 10.1086/313818.
    1. Achilles SL, Hillier SL. The complexity of contraceptives: understanding their impact on genital immune cells and vaginal microbiota. AIDS. 2013;27(Suppl 1):S5–15. doi: 10.1097/QAD.0000000000000058.
    1. Muzny CA, Schwebke JR. Biofilms: an underappreciated mechanism of treatment failure and recurrence in vaginal infections. Clin Infect Dis. 2015. [Epub ahead of print].
    1. Turovskiy Y, Cheryian T, Algburi A, Wirawan RE, Takhistov P, Sinko PJ, et al. Susceptibility of Gardnerella vaginalis biofilms to natural antimicrobials subtilosin, epsilon-poly-L-lysine, and lauramide arginine ethyl ester. Infect Dis Obstet Gynecol. 2012;2012:284762. doi: 10.1155/2012/284762.
    1. Reichman O, Akins R, Sobel JD. Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis. Sex Transm Dis. 2009;36(11):732–4. doi: 10.1097/OLQ.0b013e3181b08456.
    1. Hymes SR, Randis TM, Sun TY, Ratner AJ. DNase inhibits gardnerella vaginalis biofilms in vitro and in vivo. J Infect Dis. 2013;207(10):1491–7. doi: 10.1093/infdis/jit047.
    1. Dukes MNG; Excerpta Medica Foundation. Side effects of drugs annual. Amsterdam, New York: Excerpta Medica; sole distributors for the USA and Canada: Elsevier/North Holland.
    1. Van Kessel K, Assefi N, Marrazzo J, Eckert L. Common complementary and alternative therapies for yeast vaginitis and bacterial vaginosis: a systematic review. Obstet Gynecol Surv. 2003;58(5):351–8.
    1. Swate TE, Weed JC. Boric acid treatment of vulvovaginal candidiasis. Obstet Gynecol. 1974;43(6):893–5.
    1. Van Slyke KK, Michel VP, Rein MF. Treatment of vulvovaginal candidiasis with boric acid powder. Am J Obstet Gynecol. 1981;141(2):145–8.
    1. Singh S, Sobel JD, Bhargava P, Boikov D, Vazquez JA. Vaginitis due to Candida krusei: epidemiology, clinical aspects, and therapy. Clin Infect Dis. 2002;35(9):1066–70. doi: 10.1086/343826.
    1. Sobel JD, Chaim W, Nagappan V, Leaman D. Treatment of vaginitis caused by Candida glabrata: use of topical boric acid and flucytosine. Am J Obstet Gynecol. 2003;189(5):1297–300. doi: 10.1067/S0002-9378(03)00726-9.
    1. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1–137.
    1. Aggarwal A, Shier RM. Recalcitrant Trichomonas vaginalis infections successfully treated with vaginal acidification. J Obstet Gynaecol Can. 2008;30(1):55–8. doi: 10.1016/S1701-2163(16)32714-1.
    1. Prutting SM, Cerveny JD. Boric acid vaginal suppositories: a brief review. Infect Dis Obstet Gynecol. 1998;6(4):191–4. doi: 10.1155/S1064744998000386.
    1. Shinohara YT, Tasker SA. Successful use of boric acid to control azole-refractory Candida vaginitis in a woman with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16(3):219–20. doi: 10.1097/00042560-199711010-00013.
    1. Van Slyke KK, Michel VP, Rein MF. The boric acid powder treatment of vulvovaginal candidiasis. J Am Coll Health Assoc. 1981;30(3):107–9. doi: 10.1080/01644300.1981.10393050.
    1. Sobel JD, Chaim W. Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy. Clin Infect Dis. 1997;24(4):649–52. doi: 10.1093/clind/24.4.649.
    1. Pulcini E. Effects of boric acid (BA) and TOL-463 against biofilms formed by key vaginitis pathogens gardnerella vaginalis and candida albicans. Infect Dis Soc Obstet Gynecol Stowe Vermont. 2014.
    1. Swidsinski A, Loening-Baucke V, Swidsinski S, Verstraelen H. Polymicrobial Gardnerella biofilm resists repeated intravaginal antiseptic treatment in a subset of women with bacterial vaginosis: a preliminary report. Arch Gynecol Obstet. 2015;291(3):605–9. doi: 10.1007/s00404-014-3484-1.
    1. Rupf S, Balkenhol M, Sahrhage TO, Baum A, Chromik JN, Ruppert K, et al. Biofilm inhibition by an experimental dental resin composite containing octenidine dihydrochloride. Dent Mater. 2012;28(9):974–84. doi: 10.1016/j.dental.2012.04.034.
    1. Hubner NO, Siebert J, Kramer A. Octenidine dihydrochloride, a modern antiseptic for skin, mucous membranes and wounds. Skin Pharmacol Physiol. 2010;23(5):244–58. doi: 10.1159/000314699.
    1. Sennhenn-Kirchner S, Wolff N, Klaue S, Mergeryan H, Borg-von Zepelin M. Decontamination efficacy of antiseptic agents on in vivo grown biofilms on rough titanium surfaces. Quintessence Int. 2009;40(10):e80–8.
    1. Bartoszewicz M, Rygiel A, Krzeminski M, Przondo-Mordarska A. Penetration of a selected antibiotic and antiseptic into a biofilm formed on orthopedic steel implants. Ortop Traumatol Rehabil. 2007;9(3):310–8.
    1. Eade CR, Cole AL, Diaz C, Rohan LC, Parniak MA, Marx P, et al. The anti-HIV microbicide candidate RC-101 inhibits pathogenic vaginal bacteria without harming endogenous flora or mucosa. Am J Reprod Immunol. 2013;69(2):150–8. doi: 10.1111/aji.12036.
    1. Hooven TA, Randis TM, Hymes SR, Rampersaud R, Ratner AJ. Retrocyclin inhibits Gardnerella vaginalis biofilm formation and toxin activity. J Antimicrob Chemother. 2012;67(12):2870–2. doi: 10.1093/jac/dks305.
    1. Brackman G, Coenye T. Quorum sensing inhibitors as anti-biofilm agents. Curr Pharm Des. 2015;21(1):5–11. doi: 10.2174/1381612820666140905114627.
    1. Deng Y, Lim A, Lee J, Chen S, An S, Dong YH, et al. Diffusible signal factor (DSF) quorum sensing signal and structurally related molecules enhance the antimicrobial efficacy of antibiotics against some bacterial pathogens. BMC Microbiol. 2014;14:51. doi: 10.1186/1471-2180-14-51.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera