Bacterial vaginosis

Bacterial vaginosis
Other names: Anaerobic vaginositis, non-specific vaginitis, vaginal bacteriosis, Gardnerella vaginitis[1]
Micrograph of bacterial vaginosis — cells of the cervix covered with rod-shaped bacteria, Gardnerella vaginalis (arrows).
SpecialtyGynecology, infectious disease
SymptomsVaginal discharge that often smells like fish, burning with urination[2]
ComplicationsEarly delivery among pregnant women[3]
CausesImbalance of the naturally occurring bacteria in the vagina[4][5]
Risk factorsDouching, new or multiple sex partners, antibiotics, using an intrauterine device[5]
Diagnostic methodTesting the vaginal discharge[6]
Differential diagnosisVaginal yeast infection, infection with Trichomonas[7]
PreventionProbiotics[6]
MedicationClindamycin or metronidazole[6]
Frequency~ 5% to 70% of women[8]

Bacterial vaginosis (BV) is a disease of the vagina caused by excessive growth of bacteria.[6][9] Common symptoms include increased vaginal discharge that often smells like fish.[2] The discharge is usually white or gray in color.[2] Burning with urination may occur.[2] Itching is uncommon.[2][6] Occasionally, there may be no symptoms.[2] Having BV approximately doubles the risk of infection by a number of sexually transmitted infections, including HIV/AIDS.[8][10] It also increases the risk of early delivery among pregnant women.[3][11]

BV is caused by an imbalance of the naturally occurring bacteria in the vagina.[4][5] There is a change in the most common type of bacteria and a hundred to thousandfold increase in total numbers of bacteria present.[6] Typically, bacteria other than Lactobacilli become more common.[12] Risk factors include douching, new or multiple sex partners, antibiotics, and using an intrauterine device, among others.[5] However, it is not considered a sexually transmitted infection.[13] Diagnosis is suspected based on the symptoms, and may be verified by testing the vaginal discharge and finding a higher than normal vaginal pH, and large numbers of bacteria.[6] BV is often confused with a vaginal yeast infection or infection with Trichomonas.[7]

Usually treatment is with an antibiotic, such as clindamycin or metronidazole.[6] These medications may also be used in the second or third trimesters of pregnancy.[6] However, the condition often recurs following treatment.[6] Probiotics may help prevent re-occurrence.[6] It is unclear if the use of probiotics or antibiotics affects pregnancy outcomes.[6][14]

BV is the most common vaginal infection in women of reproductive age.[5] The percentage of women affected at any given time varies between 5% and 70%.[8] BV is most common in parts of Africa and least common in Asia and Europe.[8] In the United States about 30% of women between the ages of 14 and 49 are affected.[15] Rates vary considerably between ethnic groups within a country.[8] While BV like symptoms have been described for much of recorded history, the first clearly documented case occurred in 1894.[1]

Signs and symptoms

Homogeneous white discharge suggestive of bacterial vaginosis

Common symptoms include increased vaginal discharge that usually smells like fish. The discharge is often white or gray in color. There may be burning with urination. Occasionally, there may be no symptoms.[2]

The discharge coats the walls of the vagina, and is usually without significant irritation, pain, or erythema (redness), although mild itching can sometimes occur. By contrast, the normal vaginal discharge will vary in consistency and amount throughout the menstrual cycle and is at its clearest at ovulation—about two weeks before the period starts. Some practitioners claim that BV can be asymptomatic in almost half of affected women,[16] though others argue that this is often a misdiagnosis.[17]

Complications

Although previously considered a mere nuisance infection, untreated bacterial vaginosis may cause increased susceptibility to sexually transmitted infections, including HIV, and pregnancy complications.[18][19]

It has been shown that HIV-infected women with bacterial vaginosis (BV) are more likely to transmit HIV to their sexual partners than those without BV.[10] Diagnostic criteria for BV have also been associated with a female genital tract factor that induces expression of HIV.[18]

There is evidence of an association between BV and increased rates of sexually transmitted infections such as HIV/AIDS.[18] BV is associated with up to a six-fold increase in HIV shedding. BV is a risk factor for viral shedding and herpes simplex virus type 2 infection. BV may increase the risk of infection with or reactivation of human papillomavirus (HPV).[18][20]

In addition, bacterial vaginosis as either pre-existing, or acquired, may increase the risk of pregnancy complications, most notably premature birth or miscarriage.[21][22] Pregnant women with BV have a higher risk of chorioamnionitis, miscarriage, preterm birth, premature rupture of membranes, and postpartum endometritis.[23] Women with BV who are treated with in vitro fertilization have a lower implantation rate and higher rates of early pregnancy loss.[18][20]

Causes

Main article: List of bacterial vaginosis microbiota

Healthy vaginal microbiota consists of species which neither cause symptoms or infections, nor negatively affect pregnancy. It is dominated mainly by Lactobacillus species.[12][24] BV is defined by the disequilibrium in the vaginal microbiota, with decline in the number of lactobacilli. While the infection involves a number of bacteria, it is believed that most infections start with Gardnerella vaginalis creating a biofilm, which allows other opportunistic bacteria to thrive.[9][25]

One of the main risks for developing BV is douching, which alters the vaginal microbiota and predisposes women to developing BV.[26] Douching is strongly discouraged by the U.S. Department of Health and Human Services and various medical authorities, for this and other reasons.[26]

BV is a risk factor for pelvic inflammatory disease, HIV, sexually transmitted infections (STIs), and reproductive and obstetric disorders or negative outcomes. It is possible for sexually inactive persons to develop bacterial vaginosis.[9]

Bacterial vaginosis may sometimes affect women after menopause. Also, subclinical iron deficiency may correlate with bacterial vaginosis in early pregnancy.[27] A longitudinal study published in February 2006, in the American Journal of Obstetrics and Gynecology, showed a link between psychosocial stress and bacterial vaginosis persisted even when other risk factors were taken into account.[28] Exposure to the spermicide nonoxynol-9 does not affect the risk of developing bacterial vaginosis.[29]

Having a female partner increases the risk of BV by 60%. The bacteria associated with BV have been isolated from male genitalia. BV microbiota has been found in the penis, coronal sulcus, and male urethra, in the male partners of infected females. Partners who have not been circumcised may act as a ‘reservoir’ increasing the likelihood of acquiring an infection after sexual intercourse. Another mode of transmission of the BV-associated microbiota is to a female sexual partner via skin-to-skin transfer. BV may be transmitted via the perineal enteric bacteria from the microbiota of the female and male genitalia.[18]

Diagnosis

A pH indicator to detect vaginal alkalinization (here showing approximately pH 8), and a microscope slide to microscopically detect clue cells.

To make a diagnosis of bacterial vaginosis, a swab from inside the vagina should be obtained. These swabs should be tested for:

  • A characteristic "fishy" odor on wet mount. This test, called the whiff test, is performed by adding a small amount of potassium hydroxide to a microscopic slide containing the vaginal discharge. A characteristic fishy odor is considered a positive whiff test and is suggestive of bacterial vaginosis.
  • Loss of acidity. To control bacterial growth, the vagina is normally slightly acidic with a pH of 3.8–4.2. A swab of the discharge is put onto litmus paper to check its acidity. A pH greater than 4.5 is considered alkaline and is suggestive of bacterial vaginosis.
  • The presence of clue cells on wet mount. Similar to the whiff test, the test for clue cells is performed by placing a drop of sodium chloride solution on a slide containing vaginal discharge. If present, clue cells can be visualized under a microscope. They are so-named because they give a clue to the reason behind the discharge. These are epithelial cells that are coated with bacteria.

Two positive results in addition to the discharge itself are enough to diagnose BV. If there is no discharge, then all three criteria are needed.[30] Differential diagnosis for bacterial vaginosis includes the following:[31]

The Center For Disease Control (CDC) defines STIs as "a variety of clinical syndromes and infections caused by pathogens that can be acquired and transmitted through sexual activity."[33] But the CDC does not specifically identify BV as sexually transmitted infection.[13]

Amsel criteria

In clinical practice BV can be diagnosed using the Amsel criteria:[30]

  1. Thin, white, yellow, homogeneous discharge
  2. Clue cells on microscopy
  3. pH of vaginal fluid >4.5
  4. Release of a fishy odor on adding alkali—10% potassium hydroxide (KOH) solution.

At least three of the four criteria should be present for a confirmed diagnosis.[34] A modification of the Amsel criteria accepts the presence of two instead of three factors and is considered equally diagnostic.

Gram stain

An alternative is to use a Gram-stained vaginal smear, with the Hay/Ison[35] criteria or the Nugent[23] criteria. The Hay/Ison criteria are defined as follows:[34]

  • Grade 1 (Normal): Lactobacillus morphotypes predominate.
  • Grade 2 (Intermediate): Some lactobacilli present, but Gardnerella or Mobiluncus morphotypes also present.
  • Grade 3 (Bacterial Vaginosis): Predominantly Gardnerella and/or Mobiluncus morphotypes. Few or absent lactobacilli. (Hay et al., 1994)

Gardnerella vaginalis is the main culprit in BV. Gardnerella vaginalis is a short rod (coccobacillus). Hence, the presence of clue cells and gram variable coccobacilli are indicative or diagnostic of bacterial vaginosis.

Nugent score

The Nugent Score is now rarely used by physicians due to the time it takes to read the slides and requires the use of a trained microscopist.[4] A score of 0-10 is generated from combining three other scores. The scores are as follows:

  • 0–3 is considered negative for BV
  • 4–6 is considered intermediate
  • 7+ is considered indicative of BV.

At least 10–20 high power (1000× oil immersion) fields are counted and an average determined.

Lactobacillus morphotypes — average per high powered (1000× oil immersion) field. View multiple fields.

Gardnerella / Bacteroides morphotypes — average per high powered (1000× oil immersion) field. View multiple fields.

Curved Gram variable rods — average per high powered (1000× oil immersion) field. View multiple fields (note that this factor is less important — scores of only 0–2 are possible)

  • Score 0 for >30
  • Score 1 for 15–30
  • Score 2 for 14
  • Score 3 for <1 (this is an average, so results can be >0, yet <1)
  • Score 4 for 0
  • Score 0 for 0
  • Score 1 for <1 (this is an average, so results can be >0, yet <1)
  • Score 2 for 1–4
  • Score 3 for 5–30
  • Score 4 for >30
  • Score 0 for 0
  • Score 1 for <5
  • Score 2 for 5+

DNA hybridization testing with Affirm VPIII was compared to the Gram stain using the Nugent criteria.[36] The Affirm VPIII test may be used for the rapid diagnosis of BV in symptomatic women but uses expensive proprietary equipment to read results, and does not detect other pathogens that cause BV, including Prevotella spp, Bacteroides spp, & Mobiluncus spp.

Screening

Screening during pregnancy is not recommended in the United States as of 2020.[37]

Prevention

Some steps suggested to lower the risk include: not douching, avoiding sex, or limiting the number of sex partners.[38]

One review concluded that probiotics may help prevent re-occurrence.[6] Another review found that, while there is tentative evidence, it is not strong enough to recommend their use for this purpose.[39]

Early evidence suggested that antibiotic treatment of male partners could re-establish the normal microbiota of the male urogenital tract and prevent the recurrence of infection.[18] However, a 2016 Cochrane review found high-quality evidence that treating the sexual partners of women with bacterial vaginosis had no effect on symptoms, clinical outcomes, or recurrence in the affected women. It also found that such treatment may lead treated sexual partners to report increased adverse events.[18]

Treatment

Antibiotics

Treatment is typically with the antibiotics metronidazole or clindamycin.[40] They can be either given by mouth or applied inside the vagina.[40] About 10% to 15% of people, however, do not improve with the first course of antibiotics and recurrence rates of up to 80% have been documented.[20] Recurrence rates are increased with sexual activity with the same pre-/posttreatment partner and inconsistent condom use although estrogen-containing contraceptives decrease recurrence.[41] When clindamycin is given to pregnant women symptomatic with BV before 22 weeks of gestation the risk of pre-term birth before 37 weeks of gestation is lower.[42]

Other antibiotics that may work include macrolides, lincosamides, nitroimidazoles, and penicillins.[18]

Bacterial vaginosis is not considered a sexually transmitted infection, and treatment of a male sexual partner of a woman with bacterial vaginosis is not recommended.[43][44]

Probiotics

A 2009 Cochrane review found tentative but insufficient evidence for probiotics as a treatment for BV.[20] A 2014 review reached the same conclusion.[45] A 2013 review found some evidence supporting the use of probiotics during pregnancy.[46] The preferred probiotics for BV are those containing high doses of lactobacilli (around 109 CFUs) given in the vagina.[47] Intravaginal administration is preferred to taking them by mouth.[47] Prolonged repetitive courses of treatment appear to be more promising than short courses.[47]

Antiseptics

Topical antiseptics, for example dequalinium chloride, policresulen, hexetidine or povidone-iodine vaginal suppositories may be applied, if the risk of ascending infections is low (outside of pregnancy and in immunocompetent patients without histories of upper genital tract infections).[48] One study found that vaginal irrigations with hydrogen peroxide (3%) resulted in a slight improvement but this was much less than with the use of oral metronidazole.[49]

Epidemiology

BV is the most common infection of the vagina in women of reproductive age.[5] The percentage of women affected at any given time varies between 5% and 70%.[8] BV is most common in parts of Africa, and least common in Asia and Europe.[8] In the United States, about 30% of those between the ages of 14 and 49 are affected.[15] Rates vary considerably between ethnic groups within a country.[8]

References

  1. 1 2 Borchardt, Kenneth A. (1997). Sexually transmitted diseases : epidemiology, pathology, diagnosis, and treatment. Boca Raton [u.a.]: CRC Press. p. 4. ISBN 9780849394768. Archived from the original on 10 September 2017.
  2. 1 2 3 4 5 6 7 "What are the symptoms of bacterial vaginosis?". 21 May 2013. Archived from the original on 2 April 2015. Retrieved 3 March 2015.
  3. 1 2 Queena JT, Spong CY, Lockwood CJ, eds. (2012). Queenan's management of high-risk pregnancy : an evidence-based approach (6th ed.). Chichester, West Sussex: Wiley-Blackwell. p. 262. ISBN 9780470655764.
  4. 1 2 3 Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 9781455748013.
  5. 1 2 3 4 5 6 "Bacterial Vaginosis (BV): Condition Information". National Institute of Child Health and Human Development. 21 May 2013. Archived from the original on 2 April 2015. Retrieved 3 March 2015.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 Donders GG, Zodzika J, Rezeberga D (April 2014). "Treatment of bacterial vaginosis: what we have and what we miss". Expert Opinion on Pharmacotherapy. 15 (5): 645–57. doi:10.1517/14656566.2014.881800. PMID 24579850. S2CID 19241611.
  7. 1 2 Mashburn J (2006). "Etiology, diagnosis, and management of vaginitis". Journal of Midwifery & Women's Health. 51 (6): 423–30. doi:10.1016/j.jmwh.2006.07.005. PMID 17081932.
  8. 1 2 3 4 5 6 7 8 Kenyon C, Colebunders R, Crucitti T (December 2013). "The global epidemiology of bacterial vaginosis: a systematic review". American Journal of Obstetrics and Gynecology. 209 (6): 505–23. doi:10.1016/j.ajog.2013.05.006. PMID 23659989.
  9. 1 2 3 Sharma H, Tal R, Clark NA, Segars JH (January 2014). "Microbiota and pelvic inflammatory disease". Seminars in Reproductive Medicine. 32 (1): 43–9. doi:10.1055/s-0033-1361822. PMC 4148456. PMID 24390920.
  10. 1 2 Bradshaw CS, Brotman RM (July 2015). "Making inroads into improving treatment of bacterial vaginosis - striving for long-term cure". BMC Infectious Diseases. 15: 292. doi:10.1186/s12879-015-1027-4. PMC 4518586. PMID 26219949.
  11. ↑ "What are the treatments for bacterial vaginosis (BV)?". National Institute of Child Health and Human Development. 15 July 2013. Archived from the original on 2 April 2015. Retrieved 4 March 2015.
  12. 1 2 Nardis C, Mosca L, Mastromarino P (September–October 2013). "Vaginal microbiota and viral sexually transmitted diseases". Annali di Igiene. 25 (5): 443–56. doi:10.7416/ai.2013.1946. PMID 24048183.
  13. 1 2 "Bacterial Vaginosis – CDC Fact Sheet". Centers for Disease Control and Prevention. 11 March 2014. Archived from the original on 28 February 2015. Retrieved 2 March 2015.
  14. ↑ Othman M, Neilson JP, Alfirevic Z (January 2007). "Probiotics for preventing preterm labour". The Cochrane Database of Systematic Reviews (1): CD005941. doi:10.1002/14651858.CD005941.pub2. PMID 17253567.
  15. 1 2 "Bacterial Vaginosis (BV) Statistics Prevalence". cdc.gov. 14 September 2010. Archived from the original on 22 February 2015. Retrieved 3 March 2015.
  16. ↑ Schwebke JR (December 2000). "Asymptomatic bacterial vaginosis: response to therapy". American Journal of Obstetrics and Gynecology. 183 (6): 1434–9. doi:10.1067/mob.2000.107735. PMID 11120507.
  17. ↑ Forney LJ, Foster JA, Ledger W (November 2006). "The vaginal flora of healthy women is not always dominated by Lactobacillus species". The Journal of Infectious Diseases. 194 (10): 1468–9, author reply 1469–70. doi:10.1086/508497. PMID 17054080.
  18. 1 2 3 4 5 6 7 8 9 Amaya-Guio J, Viveros-Carreño DA, Sierra-Barrios EM, Martinez-Velasquez MY, Grillo-Ardila CF (October 2016). "Antibiotic treatment for the sexual partners of women with bacterial vaginosis". The Cochrane Database of Systematic Reviews. 10: CD011701. doi:10.1002/14651858.CD011701.pub2. PMC 6458027. PMID 27696372.
  19. ↑ "STD Facts — Bacterial Vaginosis (BV)". CDC. Archived from the original on 3 December 2007. Retrieved 4 December 2007.
  20. 1 2 3 4 Senok AC, Verstraelen H, Temmerman M, Botta GA (October 2009). "Probiotics for the treatment of bacterial vaginosis". The Cochrane Database of Systematic Reviews (4): CD006289. doi:10.1002/14651858.CD006289.pub2. PMID 19821358.
  21. ↑ Bacterial vaginosis Archived 9 February 2014 at the Wayback Machine from National Health Service, UK. Page last reviewed: 03/10/2013
  22. ↑ Hillier SL, Nugent RP, Eschenbach DA, Krohn MA, Gibbs RS, Martin DH, et al. (December 1995). "Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. The Vaginal Infections and Prematurity Study Group". The New England Journal of Medicine. 333 (26): 1737–42. doi:10.1056/NEJM199512283332604. PMID 7491137.
  23. 1 2 Nugent RP, Krohn MA, Hillier SL (February 1991). "Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation". Journal of Clinical Microbiology. 29 (2): 297–301. doi:10.1128/JCM.29.2.297-301.1991. PMC 269757. PMID 1706728.
  24. ↑ Petrova MI, Lievens E, Malik S, Imholz N, Lebeer S (2015). "Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health". Frontiers in Physiology. 6: 81. doi:10.3389/fphys.2015.00081. PMC 4373506. PMID 25859220.
  25. ↑ Patterson JL, Stull-Lane A, Girerd PH, Jefferson KK (February 2010). "Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes". Microbiology. 156 (Pt 2): 392–9. doi:10.1099/mic.0.034280-0. PMC 2890091. PMID 19910411.
  26. 1 2 Cottrell BH (2010). "An updated review of evidence to discourage douching". MCN. The American Journal of Maternal Child Nursing. 35 (2): 102–7, quiz 108–9. doi:10.1097/NMC.0b013e3181cae9da. PMID 20215951. S2CID 46715131.
  27. ↑ Verstraelen H, Delanghe J, Roelens K, Blot S, Claeys G, Temmerman M (July 2005). "Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early pregnancy". BMC Infectious Diseases. 5 (1): 55. doi:10.1186/1471-2334-5-55. PMC 1199597. PMID 16000177.
  28. ↑ Nansel TR, Riggs MA, Yu KF, Andrews WW, Schwebke JR, Klebanoff MA (February 2006). "The association of psychosocial stress and bacterial vaginosis in a longitudinal cohort". American Journal of Obstetrics and Gynecology. 194 (2): 381–6. doi:10.1016/j.ajog.2005.07.047. PMC 2367104. PMID 16458633.
  29. ↑ Wilkinson D, Ramjee G, Tholandi M, Rutherford G (2002). "Nonoxynol-9 for preventing vaginal acquisition of sexually transmitted infections by women from men". The Cochrane Database of Systematic Reviews (4): CD003939. doi:10.1002/14651858.CD003939. PMID 12519623.
  30. 1 2 Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK (January 1983). "Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations". The American Journal of Medicine. 74 (1): 14–22. doi:10.1016/0002-9343(83)91112-9. PMID 6600371.
  31. ↑ "Diseases Characterized by Vaginal Discharge". cdc.gov. Centers for Disease Control and Prevention. Archived from the original on 11 July 2017.
  32. ↑ Donders GG, Vereecken A, Bosmans E, Dekeersmaecker A, Salembier G, Spitz B (January 2002). "Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis". BJOG. 109 (1): 34–43. doi:10.1111/j.1471-0528.2002.00432.x. hdl:10067/1033820151162165141. PMID 11845812.
  33. ↑ Workowski KA, Bolan GA (June 2015). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and Reports. 64 (RR-03): 1–137. PMC 5885289. PMID 26042815.
  34. 1 2 "National guideline for the management of bacterial vaginosis (2006)". Clinical Effectiveness Group, British Association for Sexual Health and HIV (BASHH). Archived from the original on 3 November 2008. Retrieved 16 August 2008.
  35. ↑ Ison CA, Hay PE (December 2002). "Validation of a simplified grading of Gram stained vaginal smears for use in genitourinary medicine clinics". Sexually Transmitted Infections. 78 (6): 413–5. doi:10.1136/sti.78.6.413. PMC 1758337. PMID 12473800.
  36. ↑ Gazi H, Degerli K, Kurt O, Teker A, Uyar Y, Caglar H, et al. (November 2006). "Use of DNA hybridization test for diagnosing bacterial vaginosis in women with symptoms suggestive of infection". Apmis. 114 (11): 784–7. doi:10.1111/j.1600-0463.2006.apm_485.x. PMID 17078859.
  37. ↑ Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, et al. (April 2020). "Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: US Preventive Services Task Force Recommendation Statement". JAMA. 323 (13): 1286–1292. doi:10.1001/jama.2020.2684. PMID 32259236.
  38. ↑ "Bacterial Vaginosis – CDC Fact Sheet". Centers for Disease Control and Prevention. 11 March 2014. Archived from the original on 7 May 2015. Retrieved 6 May 2015.
  39. ↑ Mastromarino P, Vitali B, Mosca L (July 2013). "Bacterial vaginosis: a review on clinical trials with probiotics" (PDF). The New Microbiologica. 36 (3): 229–38. PMID 23912864. Archived (PDF) from the original on 18 May 2015.
  40. 1 2 Oduyebo OO, Anorlu RI, Ogunsola FT (July 2009). Oduyebo OO (ed.). "The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant women". The Cochrane Database of Systematic Reviews (3): CD006055. doi:10.1002/14651858.CD006055.pub2. PMID 19588379.
  41. ↑ Bradshaw CS, Vodstrcil LA, Hocking JS, Law M, Pirotta M, Garland SM, et al. (March 2013). "Recurrence of bacterial vaginosis is significantly associated with posttreatment sexual activities and hormonal contraceptive use". Clinical Infectious Diseases. 56 (6): 777–86. doi:10.1093/cid/cis1030. PMID 23243173.
  42. ↑ Lamont RF, Nhan-Chang CL, Sobel JD, Workowski K, Conde-Agudelo A, Romero R (September 2011). "Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis". American Journal of Obstetrics and Gynecology. 205 (3): 177–90. doi:10.1016/j.ajog.2011.03.047. PMC 3217181. PMID 22071048.
  43. ↑ Mehta SD (October 2012). "Systematic review of randomized trials of treatment of male sexual partners for improved bacteria vaginosis outcomes in women". Sexually Transmitted Diseases. 39 (10): 822–30. doi:10.1097/OLQ.0b013e3182631d89. PMID 23007709. S2CID 36148239.
  44. ↑ Potter J (November 1999). "Should sexual partners of women with bacterial vaginosis receive treatment?". The British Journal of General Practice. 49 (448): 913–8. PMC 1313567. PMID 10818662. Archived from the original on 26 April 2020. Retrieved 22 March 2010.
  45. ↑ Huang H, Song L, Zhao W (June 2014). "Effects of probiotics for the treatment of bacterial vaginosis in adult women: a meta-analysis of randomized clinical trials". Archives of Gynecology and Obstetrics. 289 (6): 1225–34. doi:10.1007/s00404-013-3117-0. PMID 24318276. S2CID 9696920.
  46. ↑ VandeVusse L, Hanson L, Safdar N (2013). "Perinatal outcomes of prenatal probiotic and prebiotic administration: an integrative review". The Journal of Perinatal & Neonatal Nursing. 27 (4): 288–301, quiz E1-2. doi:10.1097/jpn.0b013e3182a1e15d. PMID 24164813.
  47. 1 2 3 Mastromarino P, Vitali B, Mosca L (July 2013). "Bacterial vaginosis: a review on clinical trials with probiotics". The New Microbiologica. 36 (3): 229–38. PMID 23912864.
  48. ↑ Schaefer C, Spielmann H, Vetter K, eds. (January 2006). "Spezielle Arzneimitteltherapie in der Schwangerschaft" [Special medicamentous therapies in pregnancy]. Arzneiverordnung in Schwangerschaft und Stillzeit (in Deutsch) (7th ed.). Urban & Fischer. pp. 33–557. doi:10.1016/B978-343721332-8.50004-1. ISBN 978-3-437-21332-8. PMC 7271219.
  49. ↑ Verstraelen H, Verhelst R, Roelens K, Temmerman M (June 2012). "Antiseptics and disinfectants for the treatment of bacterial vaginosis: a systematic review". BMC Infectious Diseases. 12: 148. doi:10.1186/1471-2334-12-148. PMC 3458956. PMID 22742642.
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