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Women's Health

Bacterial Vaginosis: Diagnosis and Therapy

Brian L. Elkins, MD; E. J. Mayeaux Jr, MD

Common Clinical Scenario: A 32-year-old woman who recently moved to your city presents for her first prenatal visit with you at 26 weeks of pregnancy. Her only prior pregnancy resulted in a preterm delivery at 32 weeks. No underlying cause for the preterm labor was found. She is otherwise healthy, and her prenatal care to date has been unremarkable. Cervical length has been checked and is normal. Examination reveals a relatively asymptomatic vaginal discharge which screens positive for bacterial vaginosis. She wants to know if she should be treated. What do you advise?

The prevalence of symptomatic bacterial vaginosis (BV) ranges from 10% to 40%, depending on the population studied.1 Patients commonly self-treat any vaginal symptoms as a candidal infection, but such self-diagnosis—or even clinician diagnosis of vaginal symptoms by history—is often incorrect.2,3 Bacterial vaginosis and candidiasis cannot be differentiated by history alone.3

A complete examination—including visual inspection, wet-mount analysis, and pH evaluation—is essential for accurate diagnosis of any vaginal discharge. Sexually transmitted infections (STIs) must also be considered, necessitating a detailed sexual history.

PATHOLOGY

Bacterial vaginosis is a clinical syndrome resulting from an alteration in the bacterial makeup of the vaginal ecosystem. It is classified as a vaginosis (as opposed to a vaginitis) because it is confined to epithelial involvement without tissue infection.

Bacterial vaginosis is associated with activities and conditions that alter vaginal flora or pH, including douching, multiple sexual partners, and STIs.4-8 It has been linked to gynecologic infections, including endometritis, acute salpingitis, and pelvic-cuff cellulitis.4,9 It has also been implicated in adverse pregnancy outcomes—ie, first-trimester miscarriage, premature rupture of membranes, preterm labor, and preterm birth—especially in women with previous preterm deliveries.10-12

Hydrogen peroxide–producing lactobacilli are the most common organisms in normal vaginal flora but are present in only 35% of women with BV, raising the vaginal pH to accommodate a wide variety of other bacteria.4,13,14 This environment also increases the risk of acquiring human immunodeficiency virus.15-18

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DIAGNOSIS

The patient should be questioned about vaginal discharge, itching, odor, irritation, dysuria, and pelvic discomfort. The history should include the use of antibiotics or other medications before or after symptom development, douching habits, and a brief sexual history. Douching predisposes women to BV and can also lower the yield for diagnostic tests.4,19 The prevalence of BV is also greater among women with high-risk sexual practices and among women who have sex with women.20,21

Careful inspection of the external genitalia and speculum examination will reveal any inflammation and discharge. Chlamydia and gonorrhea assays or cultures may be performed in sexually active women based on history or clinical suspicion. A bimanual examination should also be performed. The differential diagnosis of BV is summarized in Table 1.

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TABLE 1. Diagnostic Values for Differential Diagnosis of Vaginal Infections

The gold standard for diagnosis of BV remains the Gram stain using Nugent’s criteria, but most health care offices no longer have this equipment. The diagnosis can be established clinically using the Amsel criteria to confirm 3 of the following 4 signs: a homogeneous, off-white, creamy discharge that adheres to the vaginal walls; clue cells (Figure); a pH of ≥4.5; and a fishy odor before or after the addition of 10% potassium hydroxide solution to a wet-mount slide.6,7

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FIGURE. Clue cells.

Several rapid diagnostic kits have been developed for BV, including kits for the simplified application of Amsel’s criteria. Over-the-counter tests are also available for patients to screen for BV via vaginal fluid pH. A colorimetric test for Gardnerella vaginalis proline iminopeptidase activity is available (QuickVue Advance G. vaginalis test), but its results are not considered diagnostic apart from Amsel’s criteria.22 A commercial DNA hybridization test is available (Affirm VPIII), which may simplify testing, but it has similar sensitivity and specificity as the conventional diagnostic methods.23 Also, because BV is polymicrobial and includes bacteria that are present in normal vaginal flora, cultures are not useful in diagnosis.14

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THERAPY

The principal goal of BV treatment in nonpregnant patients is to relieve symptoms (Table 2).4 Both clindamycin and metronidazole produce high clinical cure rates, although clindamycin cream may be less efficacious than the metronidazole regimens.4 Oral medication is more convenient but may lead to a higher rate of systemic side effects than intravaginal dosing, and patients using intravaginal products report greater satisfaction with treatment.24

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TABLE 2. Treatment of Bacterial Vaginosis4

Oral metronidazole can produce a disulfiram-type reaction if the patient drinks alcohol while using the medication, and oral clindamycin is associated with the rare but potentially fatal pseudomembranous colitis. The intravaginal preparations of these drugs carry the same warnings as their oral counterparts but yield much lower serum concentrations.

Tinidazole, a nitroimidazole that is chemically related to metronidazole, was approved by the FDA for the treatment of BV in 2007. Its principal advantages over metronidazole include once-daily dosing, shorter duration of therapy, and possibly fewer side effects such as nausea. Regimens include tinidazole, 2 g orally once daily for 2 days, or 1 g orally once daily for 5 days. Alcohol should be avoided during and 3 days after taking tinidazole due to its longer half-life.25,26

Bacterial vaginosis often recurs within 1 to 2 months posttreatment, so twice-weekly intravaginal metronidazole gel, 0.75%, may be used for suppression.27 To date, there is no evidence to support consumption of lactobacilli-containing foods or supplements as prophylaxis for BV. The CDC does not advocate treatment of sexual partners, as this does not increase the cure rate or reduce recurrence.4,28

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Pregnancy

The screening and treatment of BV in asymptomatic pregnant women remain controversial. BV confers a risk of preterm birth and is present in up to one-third of pregnant women in the United States; while antibiotic therapy can effectively eradicate infection, it does not reduce this risk in low-risk women.11,29,30 Therefore, screening and treatment of women at low risk of preterm delivery are not recommended.31 A Cochrane review in 2007 suggested that treatment of asymptomatic BV reduced some adverse pregnancy outcomes in women with a prior preterm birth and in women treated prior to 20 weeks’ gestation.30 Although further studies are needed, screening and treatment of women at high risk of preterm delivery (particularly of those with a history of prior preterm birth) may be considered pending further evidence. If screening is undertaken, it should be done at the first prenatal visit, with follow-up one month after completion of therapy.4

While it is unknown whether treating symptomatic BV in pregnant women alters pregnancy outcomes, most clinicians elect to treat symptomatic patients.32 Clindamycin and metronidazole are currently listed as pregnancy category B; they cross the placenta but have not been associated with congenital defects.33 Intravaginal clindamycin was associated with an increased incidence of adverse pregnancy outcomes in some studies involving use from 16 to 32 weeks’ gestation and is not recommended in the second half of pregnancy.4 Tinidazole has not been studied in pregnant women and is designated pregnancy category C.25 Recommended treatment options for pregnant women include oral clindamycin or metronidazole and are summarized in Table 2.

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Gynecologic Surgery

Asymptomatic BV has been associated with vaginal cuff infection after hysterectomy and with postabortion endometritis, so that screening and treatment may reduce the incidence of these complications.34 Thus, it may be reasonable to screen for and treat BV prior to uterine curettage or hysterectomy, but there are no data to support risk reduction or cost-effectiveness.

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CONCLUSION

The maintenance of normal vaginal pH and flora is extremely important for the health of the vaginal ecosystem. Physicians should consistently use the standard criteria to confirm the presence of BV, so that cases can be diagnosed and treated promptly, reducing patient discomfort and possible complications. Although more studies are needed, consideration may be given to screening asymptomatic, at-risk pregnant patients and patients undergoing gynecologic surgery.

Key Points

Bacterial vaginosis (BV) is a common cause of vaginal discharge. It has also been implicated in more serious upper genital tract infections and increases the risks for human immunodeficiency virus and preterm delivery. Patient self-diagnosis and clinician diagnosis by history often incorrectly presume candidiasis. The prevalence of BV appears to be higher among women who have high-risk sexual practices and/or have sex with women. The complaint of vaginal discharge requires clinical and microscopic examination using the Amsel criteria for BV. Commercial products are available to simplify the diagnosis of BV, but they are not superior to conventional methods. It is reasonable to screen for BV early in pregnancy in those women who are at high risk of preterm delivery; they can be treated with oral clindamycin or metronidazole. Intravaginal clindamycin is not recommended beyond the first half of pregnancy.

Answer to question posed in clinical scenario above: You counsel her that there is some evidence that treatment may reduce the recurrence rate of preterm birth. After this discussion, she elects to be treated.

The authors report no actual or potential conflicts of interest in relation to this article.

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Brian L. Elkins, MD, is Associate Professor of Clinical Family Medicine, Department of Family Medicine; E. J. Mayeaux Jr, MD, is Professor of Family Medicine, and Obstetrics and Gynecology. Both are at Louisiana State University Health Sciences Center, Shreveport.

References

1. O’Brien RF. Bacterial vaginosis: many questions—any answers? Curr Opin Pediatr. 2005;17(4):473-479.
2. Ferris DG, Nyirjesy P, Sobel JD, Soper D, Pavletic A, Litaker MS. Over-the-counter antifungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet Gynecol. 2002;99(3):419-425.
3. Landers DV, Wiesenfeld HC, Heine RP, Krohn MA, Hillier SL. Predictive value of the clinical diagnosis of lower genital tract infection in women. Am J Obstet Gynecol. 2004;190(4):1004-1010.
   
4. Sexually transmitted diseases treatment guidelines 2006. Centers for Disease Control and Prevention. MMWR Recomm Rep. 2006;55(RR-11):1-100.
5. Zhang J, Thomas AG, Leybovich E. Vaginal douching and adverse health effects: a meta-analysis. Am J Public Health. 1997;87(7):1207-1211.
6. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation. J Clin Microbiol. 1991;29(2):297-301.
7. Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983;74(1):14-22.
8. Hanna NF, Taylor-Robinson D, Kalodiki-Karamanoli M, Harris JR, McFadyen IR. The relationship between vaginal pH and the microbial status in vaginitis. Br J Obstet Gynaecol. 1985;92(12):1267-1271.
9. Soper DE, Brockwell NJ, Dalton HP, Johnson D. Observations concerning the microbial etiology of acute salpingitis. Am J Obstet Gynecol. 1994;170(4):1008-1017.
10. Morales WJ, Schorr S, Albritton J. Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Am J Obstet Gynecol. 1994;171(2): 345-349.
11. Flynn CA, Helwig AL, Meurer LN. Bacterial vaginosis in pregnancy and risk of prematurity: a meta-analysis. J Fam Pract. 1999;48(11):885-892.
12. Ralph SG, Rutherford AJ, Wilson JD. Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study. BMJ. 1999;319(7204):220-223.
13. Holst E, Wathne B, Hovelius B, Mardh PA. Bacterial vaginosis: microbiological and clinical findings. Eur J Clin Microbiol. 1987;6(5):536-541.
14. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med. 2005;353(18):1899-1911.
15. Martin HL, Richardson BA, Nyange PM, et al. Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis. 1999;180(6):1863-1868.
16. Taha TE, Hoover DR, Dallabetta GA, et al. Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS. 1998;12(13): 1699-1706.
17. Sturm-Ramirez K, Gaye-Diallo A, Eisen G, Mboup S, Kanki PJ. High levels of tumor necrosis factor-alpha and interleukin-1beta in bacterial vaginosis may increase susceptibility to human immunodeficiency virus. J Infect Dis. 2000;182(2):467-473.
18. Cu-Uvin S, Hogan JW, Caliendo AM, et al. Association between bacterial vaginosis and expression of human immunodeficiency virus type 1 RNA in the female genital tract. Clin Infect Dis. 2001;33(6):894-896.
19. 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;(12): 786-794.
20. 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):1307-1313.
21. Skinner CJ, Stokes J, Kirlew Y, Kavanagh J, Forster GE. A case-controlled study of the sexual health needs of lesbians. Genitourin Med. 1996;72(4):277-280.
22. QuickVue Advance G. vaginalis test [package insert]. San Diego, CA: Quidel Corp. 2007. www.quidel.com/libraries/pkginserts/RD/QVAdvGvag.pdf. Accessed August 2, 2009.
23. Boggess KA, Trevett TN, Madianos PN, et al. Use of DNA hybridization to detect vaginal pathogens associated with bacterial vaginosis among asymptomatic pregnant women. Am J Obstet Gynecol. 2005;193(3 pt 1): 752-756.
24. Ferris DG, Litaker MS, Woodward L, Mathis D, Hendrich J. Treatment of bacterial vaginosis: a comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. J Fam Pract. 1995;41(5):443-449.
25. Tindamax (tinidazole) [prescribing information]. San Antonio, TX: Mission Pharmaceutical Co, 2007. www.missionpharmacal.com/Global_Content/Package_ Inserts/Tindamax.pdf. Accessed June 16, 2009.
26. Flagyl (metronidazole) [prescribing information]. New York, NY: Pfizer Inc, 2006. www.pfizer.com/files/products/uspi_flagyl.pdf. Accessed June 16, 2009.
27. Sobel JD, Ferris D, Schwebke J, et al. Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis. Am J Obstet Gynecol. 2006;194(5):1283-1289.
28. Moi H, Erkkola R, Jerve F, et al. Should male consorts of women with bacterial vaginosis be treated? Genitourin Med. 1989;65(4):263-268.
29. Klebanoff MA, Hillier SL, Nugent RP, et al. Is bacterial vaginosis a stronger risk factor for preterm birth when it is diagnosed earlier in gestation? Am J Obstet Gynecol. 2005; 192(2):470-477.
30. McDonald H, Brocklehurst P, Gordon A. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. 2007;(1):CD000262.
31. US Preventive Services Task Force. Screening for bacterial vaginosis in pregnancy to prevent preterm delivery: US Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2008;148(3):214-219.
32. Leitich H, Brunbauer M, Bodner-Adler B, Kaider A, Egarter C, Husslein P. Antibiotic treatment of bacterial vaginosis in pregnancy: a meta-analysis. Am J Obstet Gynecol. 2003; 188(3):752-758.
33. Caro-Paton T, Carvajal A, Martin de Diego I, Martin-Arias LH, Alvarez Requejo A, Rodriguez Pinilla E. Is metronidazole teratogenic? A meta-analysis. Br J Clin Pharmacol. 1997;44(2):179-182.
34. Koumans EH, Kendrick JS; CDC Bacterial Vaginosis Working Group. Preventing adverse sequelae of bacterial vaginosis: public health program and research agenda. Sex Transm Dis. 2001;28(5):292-297.

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