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Disclosures: Jack D Sobel, MD Nothing to disclose. Robert L Barbieri, MD Nothing to disclose. Vanessa A Barss, MD Employee of UpToDate, Inc. Equity Ownership/Stock Options: Merck; Pfizer; Abbvie.
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INTRODUCTION — Bacterial vaginosis (BV) is the most common cause of vaginal discharge in women of childbearing age, accounting for 40 to 50 percent of cases [1-3]. In the United States, the National Health and Nutrition Examination Survey (NHANES), which included results from self-collected vaginal swabs from over 3700 women, estimated the prevalence of BV was 29 percent in the general population of women aged 14 to 49 years and 50 percent in African-American women . This included both symptomatic and asymptomatic infection. Worldwide, BV is common among women of reproductive age, with variations according to the population studied .
The absence of inflammation is the basis for the term "vaginosis" rather than "vaginitis."
PATHOGENESIS AND MICROBIOLOGY — Bacterial vaginosis (BV) represents a complex change in the vaginal flora characterized by a reduction in concentration of the normally dominant hydrogen-peroxide producing lactobacilli and an increase in concentration of other organisms, especially anaerobic gram negative rods [6-9]. The major bacteria detected are Gardnerella vaginalis, Prevotella species, Porphyromonas species, Bacteroides species, Peptostreptococcus species, Mycoplasma hominis, Ureaplasma urealyticum, and Mobiluncus species . Fusobacterium species and Atopobium vaginae are also common. The mechanism by which the floral imbalance occurs and the role of sexual activity in the pathogenesis of BV are not clear, but formation of an epithelial biofilm containing G. vaginalis appears to play an important role [10-12].
Hydrogen-peroxide producing lactobacilli appear to be important in preventing overgrowth of the anaerobes normally present in the vaginal flora. With the loss of lactobacilli, pH rises and massive overgrowth of vaginal anaerobes occurs. These anaerobes produce large amounts of proteolytic carboxylase enzymes, which break down vaginal peptides into a variety of amines that are volatile, malodorous, and associated with increased vaginal transudation and squamous epithelial cell exfoliation, resulting in the typical clinical features observed in patients with BV. (See 'Clinical features' below.) The rise in pH also facilitates adherence of G. vaginalis to the exfoliating epithelial cells.
The difference in vaginal flora between women with and without BV was illustrated in a study that used broad range DNA probes to determine the vaginal flora of 27 women with BV and 46 controls . Overall, 35 bacterial phylotypes were identified in women with BV, including 16 which were newly recognized. Women with BV had a mean of 12.6 phylotypes (range 9 to 17) per sample compared to 3.3 phylotypes (range 1 to 6) per sample in women without BV. The organisms newly identified by polymerase chain reaction (PCR) include fastidious bacteria termed “BV associated bacterium (BVAB) 1, 2 and 3” in the Clostridiales order, which appear to be specific indicators of BV .
However, increasing evidence suggests that G. vaginalis is the key player in the pathogenesis of BV and the development of a biofilm may be an essential component of this process, in addition to the gradual overgrowth of resident anaerobic vaginal flora . In this model, a cohesive form of G. vaginalis adheres to the vaginal epithelium and then becomes the scaffolding to which other species adhere . This hypothesis is supported by a study of microbiota on the epithelial surfaces of vaginal biopsy specimens from women with BV that showed a biofilm adhered to part or all of the epithelium, and G.vaginalis comprised 90 percent of bacteria in the biofilm, while Atopobium vaginae accounted for most of the remainder . Subsequent desquamation of these epithelial cells would result in the classic clue cells diagnostic of the disorder. (See 'Diagnosis' below.) In contrast, most healthy controls had unstructured accumulations of bacteria within secretions loosely attached to epithelial surfaces.
Extracellular DNA (eDNA) is a factor in the structural stability of biofilms in a variety of bacterial species and appears to play an important role in the establishment and maintenance of the G. vaginalis biofilm in BV . The presence of a biofilm may make it difficult to eradicate BV and increase the rate of recurrence, but discovery of the role of eDNA has led to the hypothesis that a DNase might be able to destroy the eDNA that helps to maintain the BV biofilm.
RISK FACTORS — Sexual activity is a risk factor for bacterial vaginosis (BV), and most experts believe that BV does not occur in women who have never had vaginal intercourse [18,19]. Epidemiologic studies are strongly supportive of sexual transmission of BV pathogens. A systematic review and meta-analysis concluded that BV is significantly associated with sexual contact with new and multiple male and female partners and decreasing the number of unprotected sexual encounters may reduce incident and recurrent infection .
There is a high occurrence of BV and concordance of flora in women who have sex with women, further suggesting sexual transmission is important [21-23]. It is not clear, however, whether one type of sexual activity may be more important in the pathogenesis of infection than another. As an example, oral-genital sex may be a more important risk factor than penile intromission into the vagina.
Among sexually active women, additional risk factors for acquisition of BV include multiple or new sexual partners, douching, and cigarette smoking [1,2,24-28]. Douching, but not other personal hygienic behaviors, appears to be causally associated with BV .
Although some degree of genetic susceptibility to BV is likely, no association between a gene polymorphism and BV has been established .
Use of condoms and estrogen-containing contraceptives may be protective factors .
CLINICAL FEATURES — Fifty to 75 percent of women with bacterial vaginosis (BV) are asymptomatic [18,32,33]. Symptomatic women typically present with vaginal discharge and/or vaginal odor [18,32,33]. The discharge is off-white, thin, and homogeneous; the odor is an unpleasant "fishy smell" that may be more noticeable after sexual intercourse and during menses .
BV alone does not cause dysuria, dyspareunia, pruritus, burning, or vaginal inflammation (erythema, edema) [32,33]. The presence of these symptoms suggests mixed vaginitis (symptoms due to two pathogens) .
DIAGNOSIS — The general diagnostic approach to women with vaginal discharge is reviewed separately. (See "Approach to women with symptoms of vaginitis".)
In clinical practice, the diagnosis of bacterial vaginosis (BV) in premenopausal women is usually based on the presence of at least three Amsel criteria (characteristic vaginal discharge, elevated pH, clue cells, fishy odor) if microscopy is available [37,38]. Use of Nugent or Hay/Ison criteria to evaluate a Gram-stained smear of vaginal discharge is the diagnostic standard in research studies, but requires more time, resources, and expertise. If microscopy is not available, the diagnosis should be based on findings on clinical examination (characteristic vaginal discharge, elevated vaginal pH, fishy odor) and results of commercial diagnostic tests. The best performing commercial diagnostic test is a DNA probe-based test for high concentrations of G. vaginalis (Affirm VP III). Acceptable alternatives include a proline-aminopeptidase test card (Pip Activity TestCard) or a test for elevated sialidase activity (OSOM BVBlue test) .
Amsel criteria — The diagnosis of BV is usually based on Amsel criteria, which are simple and useful in an office practice where microscopy is available . The first three findings are sometimes also present in patients with trichomoniasis (table 1).
Amsel criteria for diagnosis of BV (at least three criteria must be present):
●Homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls
●Vaginal pH >4.5
●Positive whiff-amine test, defined as the presence of a fishy odor when a drop of 10 percent potassium hydroxide (KOH) is added to a sample of vaginal discharge
●Clue cells on saline wet mount (picture 1A-B). Clue cells are vaginal epithelial cells studded with adherent coccobacilli that are best appreciated at the edge of the cell. For a positive result, at least 20 percent of the epithelial cells on wet mount should be clue cells. The presence of clue cells diagnosed by an experienced microscopist is the single most reliable predictor of BV .
Mobiluncus species may be noted on microscopy as well (movie 1).
Using Gram’s stain as the standard for diagnosing BV, the sensitivity of Amsel criteria for diagnosis of BV is over 90 percent and specificity is 77 percent .
Gram's stain — Gram’s stain of vaginal discharge is the gold standard for diagnosis of BV (picture 2A-B) , but is mostly performed in research studies because it requires more time, resources, and expertise than Amsel criteria [42-44]. The Gram-stained smear is evaluated using Nugent criteria (table 2) or Hay/Ison criteria (table 3). If clinical criteria are used to define infection, then reported sensitivity ranges from 62 to 100 percent .
Cytology — The Papanicolaou smear is not reliable for diagnosis of BV (sensitivity 49 percent, specificity 93 percent) . No information is available on the sensitivity and specificity of liquid-based cervical cytology screening methods. If a cytology smear suggests BV (ie, shift in flora from predominantly lactobacilli to predominantly coccobacilli with or without clue cells), the patient should be asked about symptoms, and if symptomatic, she should undergo standard diagnostic testing for BV and treatment, if appropriate. Treatment of asymptomatic women is not routinely indicated. (See 'Asymptomatic infection' below.)
Culture — Because BV represents complex changes in the vaginal flora, vaginal culture has no role in diagnosis. Although cultures for G. vaginalis are positive in almost all women with symptomatic infection, the organism is detected in up to 50 to 60 percent of healthy asymptomatic women; thus, its presence alone is not diagnostic of BV.
Commercial tests — Commercial tests for diagnosis of BV are not widely used, given the excellent performance of Amsel criteria, but can be useful when microscopy is not available.
The Affirm VP III test is an automated DNA probe assay for detecting G. vaginalis when present at a high concentration . It takes less than one hour to perform and is the best option when findings on physical examination suggest BV (characteristic vaginal discharge and results of pH and whiff test, if available), but microscopy cannot be performed to look for clue cells. In one study, for example, the combination of a positive DNA probe (concentration of G. vaginalis ≥2 times 107 CFU/mL) and vaginal pH >4.5 had a sensitivity and specificity of 95 and 99 percent, respectively, for diagnosis of BV when clinical criteria were used as the diagnostic standard . Not all studies have reproduced these excellent results, and over-diagnosis is possible.
The OSOM BVBlue system is a chromogenic diagnostic test based on the presence of elevated sialidase enzyme activity in vaginal fluid samples. This enzyme is produced by bacterial pathogens associated with bacterial vaginosis including Gardnerella, Bacteroides, Prevotella, and Mobiluncus. The test can be performed at the point of care and results are available in 10 minutes (Clinical Laboratory Improvement Amendments [CLIA]-waived). Sensitivity ranging from 88 to 94 percent and specificity ranging from 91 to 98 percent have been reported when compared with Amsel and Nugent criteria [49-51].
Investigational tests — Quantitative polymerase chain reaction (PCR)-based assays are based upon molecular quantification of G. vaginalis and Atopobium vaginae, and other bacteria [52,53]. Although these tests have good sensitivity and specificity compared with standard clinical tests , they are expensive and of questionable advantage .
A urine test that uses fluorescence in situ hybridization (FISH) to identify the BV biofilm on desquamated vaginal epithelial cells in urine sediment appears promising and is also under investigation .
Diagnosis without speculum examination — BV has been diagnosed using a swab of vaginal discharge obtained by the patient or clinician without physical examination. However, omission of the speculum examination results in under-diagnosis and should be avoided.
●In one study, young women with or without vaginitis symptoms self-tested for BV using a pH or sialidase test and results were compared with clinician-performed examination with clinical diagnosis of BV by modified Amsel criteria . Compared with diagnosis by clinician examination, self-pH was 73 percent sensitive and 67 percent specific and self-sialidase was 40 percent sensitive and 90 percent specific.
●In another study of the diagnostic accuracy for BV among women presenting with vaginal discharge to a sexually transmitted diseases (STD) clinic, all women provided self-obtained vaginal swabs for examination, completed a questionnaire, and then were examined by a clinician . A non-examining clinician reviewed the findings of the questionnaire and self-obtained vaginal swab and diagnosed BV if at least two of three Amsel criteria were positive (pH>4.5, >20 percent clue cells, positive Whiff test). Examining clinicians diagnosed BV if at least three of the four standard Amsel criteria were positive (characteristic discharge, pH>4.5, >20 percent clue cells, positive Whiff test). In all cases, Gram-stained slides for diagnosis of BV by Nugent criteria were made, but the results were not disclosed, and 125 were positive. The investigators found that clinical examination with a speculum exam was more likely to result in a correct diagnosis of BV than just examination of a self-obtained vaginal swab (90/125 versus 68/125), but also resulted in over diagnosis/over treatment in 15 patients (105 positive diagnoses versus 61 positive diagnoses).
DIFFERENTIAL DIAGNOSIS — In the absence of microscopy, a lack of fishy odor (negative whiff test) makes the diagnosis of bacterial vaginosis (BV) unlikely. BV is usually suspected because of high vaginal pH (>4.5). Other causes of increased pH include trichomoniasis, atrophic vaginitis, and desquamative inflammatory vaginitis. These four entities are easily distinguishable by clinical and microscopic features.
●Women with BV do not have dyspareunia or signs of vaginal inflammation; in contrast, women with atrophic vaginitis, desquamative inflammatory vaginitis, and trichomoniasis usually have these signs and symptoms.
●Both atrophic vaginitis and desquamative inflammatory vaginitis are associated with an increased number of parabasal cells on microscopy, which is not observed in women with BV.
●A large number of polymorphonuclear leukocytes on microscopy are characteristic of desquamative inflammatory vaginitis, trichomoniasis, and atrophic vaginitis with infection, but not BV.
●Visualization of trichomonads readily makes the diagnosis of trichomoniasis in the setting of an elevated pH, however, in other cases, we suggest using more sensitive and specific diagnostic tests to diagnose or exclude trichomoniasis.
●BV is a cause of [62-64]:
•Endometrial bacterial colonization
•Post-hysterectomy vaginal cuff cellulitis
●BV is a risk factor for human immunodeficiency virus (HIV) acquisition and transmission [65-67].
●BV is a risk factor for acquisition of herpes simplex virus type 2 (HSV-2), gonorrhea, chlamydia, and trichomonas infection [68-70]. Although BV is more common among women with pelvic inflammatory disease (PID), it is not clear whether it is a causal factor or an independent risk factor for this disease [71,72].
It has been hypothesized that the increased risk of acquisition of sexually transmitted infections in women with BV may be due to lack of hydrogen peroxide-producing lactobacilli in the vaginal flora of affected women; other factors associated with BV infection, such as local cytokine production, may also play a role.
●BV may be a factor in development of precancerous cervical lesions. In a systematic review and meta-analysis of primarily cross-sectional studies, the risk of cervical intraepithelial neoplasia (CIN) or squamous intraepithelial lesions (SIL) was increased in women with BV (OR 1.15, 95% CI 1.24-1.83); however, there was considerable heterogeneity among these studies and both CIN 1 and low-grade SIL, which do not usually progress to cancer, were included as outcomes . BV appears conducive to the persistence of human papillomavirus (HPV) infection [74,75], which is necessary but not sufficient for development of high grade cervical lesions and cancer. (See "Cervical intraepithelial neoplasia: Terminology, incidence, pathogenesis, and prevention", section on 'Role of human papillomavirus'.)
TREATMENT — Bacterial vaginosis (BV) resolves spontaneously in up to one-third of nonpregnant and one-half of pregnant women [76-79]. Treatment is indicated for relief of symptoms in women with symptomatic infection and to prevent postoperative infection in those with asymptomatic infection prior to abortion or hysterectomy (see 'Gynecologic procedures' below).
Treatment of BV may also reduce the risk of acquiring sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) [66,80]. For this reason, some experts support the concept of treating all women with BV regardless of presence or absence of symptoms; however, we agree with the United States Centers for Disease Control and Prevention (CDC) recommendations to not treat asymptomatic women.
Asymptomatic pregnant women with previous preterm births may also benefit, but screening and treatment of these women is controversial (see 'Pregnant women' below).
Drugs — Metronidazole or clindamycin administered either orally or intravaginally results in a high rate of clinical cure (70 to 80 percent at four weeks of follow-up) (table 4) [83-86]. Oral medication is more convenient, but associated with a higher rate of systemic side effects than vaginal administration. Tinidazole is a reasonable oral alternative. No new drugs have been introduced for BV therapy in the past decade.
Metronidazole — The efficacy of metronidazole has been established in randomized trials using either placebo or active drug controls [86,87]. The oral regimen we recommend is 500 mg twice daily for seven days . Treatment with a single oral dose of 2 grams of metronidazole has lower efficacy  and is no longer recommended for treatment of BV . Alcohol should not be consumed during therapy and for one day after completion of therapy.
There is little evidence of benefit from prolonging therapy longer than seven days. Most comparative studies using divided-dose oral regimens for one week achieved early cure rates in excess of 90 percent, and cure rates (by Amsel criteria) at four weeks of approximately 80 percent [84,86,89-93]. Although early cure rates are significantly higher when the initial course of metronidazole therapy is 14 days rather than 7 days, long-term cure rates (21 days after completion of therapy) are similar for both treatment regimens . Published cure rates vary widely according to the investigators’ diagnostic criteria, definition of cure and treatment failure, and length of time post-therapy before the follow-up visit.
Vaginal therapy with 0.75 percent metronidazole gel (5 grams once daily for five days) is as effective as oral metronidazole [90,91,94,95]. The choice of oral versus vaginal therapy should depend upon patient preference.
Side effects of metronidazole include a metallic taste, nausea (in 10 percent of patients), transient neutropenia (7.5 percent), a disulfiram-like effect with alcohol, prolongation of International Normalized Ratio (INR) in patients taking vitamin K antagonists (eg, warfarin), and peripheral neuropathy. Gastrointestinal side effects are less common with vaginal administration . Allergy to metronidazole is uncommon; it manifests as rash, urticaria, pruritus, and rarely, anaphylaxis, which can be successfully treated by oral desensitization .
Clindamycin — The efficacy of clindamycin has been demonstrated in a meta-analysis of randomized trials, both comparative and placebo controlled . The preferred regimen is a seven-day course of 2 percent clindamycin cream vaginally (5 grams of cream containing 100 mg of clindamycin phosphate), but may be less effective than the metronidazole regimens; nevertheless, vaginal clindamycin cream is a reasonable therapeutic choice .
Alternative regimens include oral clindamycin (300 mg twice daily for seven days) or clindamycin ovules (100 mg intravaginally once daily for three days) [37,97]. A one-day or single application of clindamycin as a bioadhesive is another option (Clindesse). These regimens have not been studied extensively and may have lower efficacy for eradicating BV.
Intravaginal clindamycin therapy has been associated with an increased prevalence of clindamycin resistant anaerobic bacteria in the vagina posttreatment (17 percent of bacterial isolates before versus 53 percent of isolates after therapy) . This effect persisted in most women for at least 90 days after clindamycin treatment. In contrast, increased resistance to metronidazole was not observed in women treated with that drug. Further investigation is required to determine the clinical implications of these findings.
Clindamycin cream should not be used concurrently with latex condoms, which may be weakened.
Pseudomembranous colitis has been reported with both oral and topical clindamycin.
Tinidazole — Tinidazole is a second generation nitroimidazole. It has a longer half-life than metronidazole (12 to 14 hours versus 6 to 7 hours) and fewer side effects , but is more costly since no generic formulation is available. If used, we suggest 1 gram orally once daily for five days, as efficacy is slightly higher and side effects are slightly less frequent than with shorter course therapy (tinidazole 2 grams orally daily for two days) . Randomized trials have shown that it is at least as effective as metronidazole, but not superior [100-104], and a single dose regimen appears to be as effective as vaginal clindamycin cream .
Secnidazole — Secnidazole is a nitroimidazole antibiotic not available in the United States, but available internationally. In a randomized double-blind non-inferiority trial, a single 2 gram oral dose of secnidazole was at least as effective as a seven-day course of 500 mg metronidazole administered orally twice daily, and was well tolerated . A single 1 gram oral dose of secnidazole appears to be as effective as the 2 gram dose .
Probiotics — Probiotics (live microorganisms which confer a health benefit on the host when administered in adequate amounts) have been used alone and as adjunctive therapy to antibiotics for treatment of BV and prevention of relapse. Systemic reviews of trials of probiotics for treatment of BV have not found sufficient evidence for or against efficacy [108,109]. Although some trials have reported very promising results, we feel the results should be reproduced in more well-designed and larger trials before use of this therapy is considered. In addition, further investigation is needed to determine the optimum route of administration (oral or vaginal), which strains or combination of strains are most effective (eg, Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC-14, Lactobacillus acidophilus), and the dose and duration of use. Lastly, the quality of commercially available probiotics varies worldwide. In the United States, the content of these products is not standardized and often of poor quality.
Less effective and ineffective therapies — Triple-sulfa creams, erythromycin, tetracycline, ampicillin, amoxicillin, lactic acid gel, acetic acid gel, ascorbic acid, azithromycin, chlorhexidine, hydrogen peroxide, and povidone-iodine vaginal douches are significantly less effective than metronidazole and clindamycin and should not be used [27,110-116]. Cure rates with ampicillin and amoxicillin are mediocre.
Follow-up — Follow-up is unnecessary if symptoms resolve .
●Male partners – It is not necessary to treat male sexual partners of affected women, as there is no strong evidence that the woman's response to therapy and risk of relapse are influenced by treatment of her male sex partner(s) [37,117]. However, the available trials are flawed; well-designed and larger trials should be performed to assess the efficacy of male partner treatment .
Sexual intercourse appears to play a role in disease activity. Some studies have reported reduced rates of recurrence when male sexual partners used condoms routinely during coitus or when women remained abstinent [27,31,119-122].
●Female partners – Women with BV who have sex with women (WSW) should encourage their partners to be aware of the signs and symptoms of BV, given the high risk of concordant infection (25 to 50 percent ). In women with confirmed infection, treatment is indicated for relief of symptoms. It has been hypothesized that behavioral interventions that reduce transfer of vaginal fluid between female sex partners may be helpful (eg, cleaning sex toys between use, use of gloves during digital-vaginal sex); however, a small randomized trial evaluating this approach reported no reduction in BV persistence . Further study is needed. (See "Medical care of women who have sex with women", section on 'Sexually transmitted diseases'.)
Relapse and recurrent infection — Approximately 30 percent of patients with initial responses to therapy have a recurrence of symptoms within three months  and more than 50 percent experience a recurrence within 12 months . The explanation for this high rate of recurrence is unclear. Reinfection is possible, but recurrence more likely reflects a failure to eradicate the offending organisms or to reestablish the normal protective vaginal flora dominated by lactobacillus. Infections involving biofilms can be more difficult to eradicate . The only interventions proven to reduce development or recurrence of BV are chronic suppressive therapy and circumcision of male partners [125,126].
We suggest symptomatic relapse be treated initially with a seven-day course of oral or vaginal metronidazole or clindamycin. The treatment regimen may be the same or different from the initial or previous treatment regimen .
After initial induction therapy, most women with a history of recurrent infection benefit from suppressive therapy to maintain an asymptomatic state. We believe any patient with more than three documented episodes of BV in the previous 12 months should be offered a long-term maintenance regimen consisting of maintenance metronidazole gel. Long-term clindamycin regimens, oral or topical, are not advised because of toxicity and lack of documented efficacy . Accordingly, if any of the aforementioned antimicrobials fail, we prescribe metronidazole gel 0.75 percent or an oral nitroimidazole for 7 to 10 days followed by twice weekly dosing of gel for four to six months . In one multicenter prospective trial of this metronidazole gel regimen, recurrent BV occurred in 25.5 percent of patients on suppressive therapy versus 59.1 percent of those receiving placebo . Secondary vaginal candidiasis was a common side effect.
Results can be improved by adding vaginal boric acid to the oral nitroimidazole induction therapy . Metronidazole or tinidazole is taken orally for seven days; vaginal boric acid 600 mg once daily at bedtime is begun at the same time and continued for 21 days. Patients are seen for follow-up a day or two after their last boric acid dose; if they are in remission, we immediately begin metronidazole gel twice weekly for four to six months as suppressive therapy. Therapy is then discontinued. Boric acid can cause death if consumed orally; patients should be told to store boric acid in a secure place that is inaccessible to children.
As discussed above, no study has demonstrated reduced rates of recurrence in women whose partners were treated with metronidazole. However, some studies have reported reduced rates of recurrence when sexual partners used condoms routinely with coitus or the patient remained abstinent [27,31,119-122]. For this reason, some experts suggest these behavioral interventions for women with recurrent infection.
A single trial has reported that use of condoms and combination metronidazole/nystatin ovule therapy may reduce the frequency of recurrent infection . The higher efficacy of the ovule may be due to the higher content of metronidazole (500 mg) compared with the gel (37.5 mg).
Exogenous lactobacillus recolonization with 30 days of oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 in addition to seven days of metronidazole therapy has been suggested, but there is minimal evidence of the efficacy of this approach [86,128]. These results should be reproduced in other trials before use of this therapy is considered.
Vaginal acidifying agents, although popular and widely used, have no role in the treatment of acute or chronic BV, as they have never been shown to enhance cure rates. Douching should be avoided. Likewise, in a randomized trial, probiotics were not more effective than placebo for prevention of relapse .
Asymptomatic infection — Treatment of asymptomatic BV is typically avoided since patients often spontaneously improve over a period of several months and any antibacterial therapy is often followed by symptomatic vaginal yeast infection. This practice is supported by a double-blind, placebo controlled trial of 54 women with asymptomatic BV who were randomly assigned to receive intravaginal metronidazole or placebo gel . There was no difference in the proportion of women in either group who noticed improvement in vaginal odor or discharge. In addition, 6 of 28 women receiving metronidazole developed symptomatic vaginal candidiasis compared with no women taking placebo.
Although some experts recommend treatment of asymptomatic BV because affected women are more susceptible to acquiring other STDs (including HIV and herpes simplex virus), available evidence is insufficient to clearly support or exclude a benefit of treatment [80,129-131].
Treatment is indicated for asymptomatic women who are scheduled for certain gynecologic procedures (see below). Treatment of asymptomatic infection in pregnant women is more complex and is discussed in detail below (see 'Pregnant women' below).
Gynecologic procedures — Evidence linking asymptomatic BV with gynecologic complications has caused this issue to be reassessed, especially with the availability of topical therapy. It is reasonable to treat asymptomatic BV prior to hysterectomy and before pregnancy termination to prevent postprocedure infection (cuff infection after hysterectomy, endometritis after abortion). Reported reductions in postoperative infectious complications range from 10 to 75 percent [132-138].
Symptomatic BV infection — All women with symptomatic BV should be treated to relieve bothersome symptoms. Oral treatment is effective and has not been associated with adverse fetal or obstetrical effects [139-144]. The therapeutic options include :
●Metronidazole 500 mg orally twice daily for 7 days
●Metronidazole 250 mg orally 3 times daily for 7 days
●Clindamycin 300 mg orally twice daily for 7 days
Some clinicians avoid use of metronidazole in the first trimester because it crosses the placenta, and thus has a potential for teratogenicity. However, meta-analysis has not found any relationship between metronidazole exposure during the first trimester of pregnancy and birth defects , and the CDC no longer discourage the use of metronidazole in the first trimester . An additional concern is that the drug is mutagenic in bacteria and carcinogenic in mice, but there is no evidence of harm in humans.
As mentioned above, topical therapy is as effective as oral therapy in the treatment of nonpregnant women with BV. In contrast, some experts avoid topical therapy in pregnant women because they believe oral treatment is more effective against potential subclinical upper genital tract infection [147-149].
Asymptomatic infection and screening — As many as one-third of pregnant women in the United States have BV . Of concern, a 2007 meta-analysis reported a statistically significant increased risk of preterm birth in these women; the pooled odds ratio for prematurity was 2.16 (95% CI 1.56-3.00) . The increased risk of preterm birth attributable to BV appears to be linked to preterm labor due to chorioamnionitis [59,151]. Other complications of BV include postpartum endometritis (OR 2.53, 95% CI 1.25-5.08), and an increased risk of late miscarriage (OR 6.32, 95% CI 3.65-10.9) .
Despite the association between BV and adverse outcome, screening and treatment of asymptomatic BV during pregnancy is controversial. Meta-analyses of randomized trials performed in general obstetric populations have generally found that treatment of asymptomatic infection does not reduce the incidence of preterm labor or delivery in the overall obstetrical population [139,152,153], but some subgroups of women, such as those at high risk for preterm birth, may benefit. The available evidence is discordant due to differences in selection of trials and differences between the included trials.
●In a 2013 Cochrane meta-analysis including 21 trials involving 7847 pregnant women with BV (symptomatic or asymptomatic) detected through screening, antibiotic therapy was highly effective in eradicating infection, but did not significantly reduce the odds of preterm birth at less than 37 weeks (OR 0.88, 95% CI 0.71-1.09) or the risk of preterm premature rupture of membranes (OR 0.74, 95% CI 0.30-1.84) . Treatment initiated before 20 weeks of gestation also did not reduce the risk of preterm birth before 37 weeks (OR 0.85, 95% CI 0.62-1.17).
When the Cochrane reviewers separately analyzed the subgroup of women with a history of one or more prior preterm births (ie, women at high risk for preterm birth), the detection and treatment of BV still did not significantly reduce the risk of preterm birth (OR 0.78, 95% CI 0.42-1.48; 3 trials, 421 women).
●In 2008, the United States Preventive Services Task Force (USPSTF) evaluated the effect of treatment of asymptomatic BV in women at high risk for preterm birth . Due to heterogeneity, results could not be pooled. Three trials showed fewer deliveries before 37 weeks of gestation with treatment, one showed no benefit, and one trial  reported an increase in preterm deliveries after treatment with metronidazole. For delivery before 34 weeks of gestation, meta-analysis was possible and showed no significant treatment benefit.
●In a 2011 meta-analysis of five randomized trials of asymptomatic women with BV at <22 weeks of gestation treated with clindamycin or placebo/no treatment, clindamycin therapy was associated with a reduction in preterm birth <37 weeks (3.7 percent [44/1183] versus 6.2 percent [72/1163]; fixed effects RR 0.60, 95% CI 0.42-0.86, random effects 0.64, 95% CI 0.39-1.05) and late miscarriage (0.3 percent [2/639] versus 1.9 percent [12/631]; RR 0.20, 95% CI 0.05-0.76) . Subgroup analysis revealed that oral, not vaginal, clindamycin therapy was associated with a significant reduction in preterm birth (oral therapy RR 0.39, 95% CI 0.20-0.76; vaginal RR 0.73, 95% CI 0.47-1.14). The analysis included a mixed population of women at both low and high risk of preterm birth.
Based upon these data, we agree with the American College of Obstetricians and Gynecologists (ACOG), USPSTF, and CDC recommendations to not routinely screen and treat all pregnant women with asymptomatic BV to prevent preterm birth and its consequences [37,152,155]. It is not possible to define specific features characterizing a subgroup of women who might respond favorably to a screening and treatment protocol. Defining these features is an active area of investigation.
As illustrated above, there may be benefits to early screening and treatment of asymptomatic pregnant women who have a history of a previous preterm delivery, but there are insufficient data to recommend this as a routine practice [141,156-159]. Further definition of high risk subgroups is under investigation. As an example, women with polymorphisms of genes regulating cytokine production (eg, tumor necrosis factor variants) have a greater proinflammatory immune response to infectious stimuli, such as BV . Enhanced induction of cytokines in these women could then lead to preterm labor or rupture of membranes. Other aspects of host response (eg, low levels of IgA to Gardnerella vaginalis) or the specific types of BV associated bacteria involved (eg, bacteria that produce high levels of sialidase or protease) may also play a role in placing some women with BV at high risk of preterm birth. (See "Risk factors for preterm labor and delivery", section on 'Infection' and "Risk factors for preterm labor and delivery", section on 'Genetic factors'.)
When treatment of BV is initiated, the optimal choice of antibiotic, timing of therapy, duration of use, and harms of therapy are also controversial. The first trials demonstrated a reduction in preterm birth in high risk women treated with oral metronidazole or oral metronidazole and erythromycin (table 5) [147-149]. However, in two studies, metronidazole use in pregnancy appeared to increase the risk of preterm birth [154,161]. This association requires further investigation and confirmation before avoiding metronidazole for treatment of BV in pregnancy. Other trials suggest that oral clindamycin given early in pregnancy is an effective therapy  and that topical clindamycin given in the second half of pregnancy is less effective and even associated with an increase in low birth weight and neonatal infection . Therefore, we use oral therapy when treatment is indicated, and consider both metronidazole and clindamycin acceptable choices.
Breastfeeding women — Clindamycin has the potential to cause adverse effects on the breastfed infant's gastrointestinal flora so the infant should be monitored for diarrhea, candidiasis (thrush, diaper rash) or, rarely, blood in the stool indicating possible antibiotic-associated colitis . Infant side effects are less likely with vaginal than oral use since only about 30 percent of a vaginal dose is absorbed.
When indicated, metronidazole is used for treatment of infection in neonates. There are no human data supporting an association between metronidazole use and cancer; however, an association with carcinogenesis in rodents has been demonstrated . Outcomes data of maternal metronidazole use did not show a significant increase in adverse events compared to use of other antimicrobials, although a cohort study found a nonsignificant trend toward more loose stools and more candidal colonization in metronidazole-exposed infants. Since the relative infant dose of metronidazole is high (29 percent) with maternal administration of the 2 gram one-time dose, a cautious approach for mothers receiving this dose is to express and discard their milk for 12 to 24 hours. This recommendation has not been extended to other metronidazole regimens.
Use of vaginal metronidazole has not been studied during breastfeeding. After vaginal administration, plasma levels are less than 2 percent of those after a 500 mg oral dose, so vaginal use of metronidazole during breastfeeding is unlikely to be of concern .
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Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient information: Bacterial vaginosis (The Basics)")
●Beyond the Basics topics (see "Patient information: Bacterial vaginosis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Bacterial vaginosis (BV) is the most common cause of vaginitis in women of childbearing age. (See 'Introduction' above.)
●BV represents a complex change in the vaginal flora characterized by a reduction in concentration of the normally dominant hydrogen-peroxide producing lactobacilli and an increase in concentration of other organisms, particularly anaerobes. (See 'Pathogenesis and microbiology' above.)
●Approximately 50 to 75 percent of women with BV are asymptomatic. Those with symptoms often present with an off-white, thin, and homogeneous "fishy smelling" discharge that is more noticeable after coitus and during menses. (See 'Clinical features' above.)
●Sequelae of BV can include an increased risk of preterm birth, plasma-cell endometritis, postpartum fever, post-hysterectomy vaginal cuff cellulitis, postabortal infection, pelvic inflammatory disease, and acquisition of other sexually transmitted infections. (See 'Consequences' above.)
●When microscopy is available, the diagnosis of BV is based on the presence of at least three of the following four Amsel criteria (see 'Diagnosis' above):
•Homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls
•Vaginal pH greater than 4.5
•Positive whiff-amine test, defined as the presence of a fishy odor when 10 percent potassium hydroxide (KOH) is added to a sample of vaginal discharge
•Clue cells on saline wet mount, comprising at least 20 percent of epithelial cells
●If microscopy is not available, we suggest using physical examination, pH testing, whiff-amine test, and a commercial test using a DNA probe (eg, Affirm VP III) to make the diagnosis of BV. (See 'Commercial tests' above.)
●Vaginal culture is not useful. (See 'Culture' above.)
Treatment of nonpregnant women
●Treatment of symptomatic women with bacterial vaginosis is indicated to reduce vaginal discharge and odor. We recommend metronidazole or clindamycin (Grade 1A). (See 'Treatment' above.) Options include:
•Metronidazole 500 mg twice daily orally for 7 days
•Metronidazole gel 0.75 percent (5 grams) once daily vaginally for 5 days
•Clindamycin 2% vaginal cream once daily at bedtime for 7 days
•Clindamycin 300 mg twice per day orally for 7 days
•Clindamycin 100 mg vaginal suppositories at bedtime for 3 days
•Clindamycin bioadhesive cream (Clindesse) 2% as a single vaginal dose of 5 grams of cream containing 100 mg of clindamycin phosphate.
●Approximately 30 percent of patients with an initial response to therapy have a recurrence of symptoms within three months and more than 50 percent experience a recurrence within 12 months. We treat symptomatic relapse with a longer course of therapy, using a different antibiotic than that used for the initial episode. For women who prefer preventive therapy instead of treatment of frequent episodes of BV, we suggest metronidazole or tinidazole orally for 7 days; vaginal boric acid 600 mg is begun at the same time and continued for 21 days (Grade 2B). Patients are seen for follow-up a day or two after their last boric acid dose; if they are in remission, we immediately begin metronidazole gel twice weekly for four to six months as suppressive therapy. (See 'Relapse and recurrent infection' above.)
●We suggest treatment of asymptomatic women who are to undergo hysterectomy (Grade 2B). Preoperative treatment decreases the frequency of postoperative infectious complications. (See 'Gynecologic procedures' above.)
Treatment of pregnant women
●Pregnant women with BV are at increased risk of preterm birth. We recommend not screening all pregnant women for BV, given there is no evidence that screening and treatment of asymptomatic infection reduces the risk of preterm birth (Grade 1A). (See 'Asymptomatic infection and screening' above.)
●We treat pregnant women with symptomatic BV infection to relieve symptoms. We prescribe clindamycin 300 mg orally twice daily for 7 days or metronidazole 500 mg orally twice daily for 7 days. (See 'Symptomatic BV infection' above.)
●We suggest treatment of asymptomatic women who are to undergo pregnancy termination (Grade 2B). Preoperative treatment decreases the frequency of postoperative infectious complications. (See 'Gynecologic procedures' above.)
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