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Literature review current through: Jun 2014. | This topic last updated: Jul 29, 2014.

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 [4]. This included both symptomatic and asymptomatic infection. Worldwide, BV is common among women of reproductive age, with variations according to the population studied [5].

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 [6]. 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 [10-13].

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 [14]. 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 [15].

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 [16]. In this model, a cohesive form of G. vaginalis adheres to the vaginal epithelium and then becomes the scaffolding to which other species adhere [17]. 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 [10]. 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 [18]. 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 [19,20]. Epidemiologic studies are strongly supportive of sexual transmission of BV pathogens. In a systematic review and meta-analysis of 43 observational studies, sexual contact with new and multiple male and female partners was associated with an increased risk of BV, while condom use was associated with a decreased risk [21].

BV is highly prevalent (25 to 50 percent) in women who have sex with women (WSW), and is associated with increasing numbers of female sexual partners, a female partner with symptomatic BV, and various sexual practices, suggesting sexual transmission is an important factor [22-26]. In a large prospective study, the two key behaviors that consistently increased the odds of BV in WSW were lifetime exposure to increased numbers of female sexual partners and having a female sexual partner with BV symptoms [25]. However, sexually active monogamous WSW partnerships over six months tended to have concordant, stable, vaginal microbiota, which was most concordant for normal flora. This suggests that longer duration, sexually active partnerships led to stability and alignment of a favorable vaginal microbiota in WSW couples.  

In addition to multiple or new sexual partners, most studies indicate douching and cigarette smoking are risk factors for acquisition of BV among sexually active women [1,2,25,27-32]. Although some degree of genetic susceptibility to BV is likely, no association between a gene polymorphism and BV has been established [33].

Use of condoms and estrogen-containing contraceptives may be protective factors [34].

CLINICAL FEATURES — Fifty to 75 percent of women with bacterial vaginosis (BV) are asymptomatic [19,35,36]. Symptomatic women typically present with vaginal discharge and/or vaginal odor [19,35,36]. 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 [37].

BV alone does not cause dysuria, dyspareunia, pruritus, burning, or vaginal inflammation (erythema, edema) [35,36]. The presence of these symptoms suggests mixed vaginitis (symptoms due to two pathogens) [38].

Although BV does not involve the cervix, the disorder may be associated with acute cervicitis (endocervical mucopurulent discharge or easily induced cervical bleeding) [39]. (See "Acute cervicitis".)

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 [40,41]. 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) [40].

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 [35]. 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 [42].

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 [43].

Gram's stain — Gram’s stain of vaginal discharge is the gold standard for diagnosis of BV (picture 2A-B) [44], but is mostly performed in research studies because it requires more time, resources, and expertise than Amsel criteria [45-47]. 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 [48].

Cytology — The Papanicolaou smear is not reliable for diagnosis of BV (sensitivity 49 percent, specificity 93 percent) [49]. 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 [50]. 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 [51]. 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 [52-54].

Investigational tests — Quantitative polymerase chain reaction (PCR)-based assays are based upon molecular quantification of G. vaginalis and Atopobium vaginae, and other bacteria [55,56]. Although these tests have good sensitivity and specificity compared with standard clinical tests [57], they are expensive and of questionable advantage [58].

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 [11].

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 [59]. 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 [60]. 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.

CONSEQUENCES

Pregnant women with bacterial vaginosis (BV) are at higher risk of preterm delivery (see 'Pregnant women' below) [61-64].

BV is a cause of [65-67]:

Endometrial bacterial colonization

Plasma-cell endometritis

Postpartum fever

Post-hysterectomy vaginal cuff cellulitis

Postabortal infection

BV is a risk factor for human immunodeficiency virus (HIV) acquisition and transmission [68-70].

BV is a risk factor for acquisition of herpes simplex virus type 2 (HSV-2), gonorrhea, chlamydia, and trichomonas infection [71-73]. 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 [74,75].

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 [76]. BV appears conducive to the persistence of human papillomavirus (HPV) infection [77,78], 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 [79-82]. 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) [69,83]. 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).

The following treatment recommendations are consistent with those of the CDC [40]. Guidelines from other organizations are available elsewhere [84,85].

Nonpregnant women

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) [86-89]. 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 [89,90]. The oral regimen we recommend is 500 mg twice daily for seven days [40]. Treatment with a single oral dose of 2 grams of metronidazole has lower efficacy [91] and is no longer recommended for treatment of BV [40]. 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 [87,89,92-96]. 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 [30]. 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 (5 grams of gel contains 37.5 mg of metronidazole) [93,94,97,98]. 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 [94]. Allergy to metronidazole is uncommon; it manifests as rash, urticaria, pruritus, and rarely, anaphylaxis, which can be successfully treated by oral desensitization [99].

Clindamycin — The efficacy of clindamycin has been demonstrated in a meta-analysis of randomized trials, both comparative and placebo controlled [89]. 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 [40].

Alternative regimens include oral clindamycin (300 mg twice daily for seven days) or clindamycin ovules (100 mg intravaginally once daily for three days) [40,100]. 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) [101]. 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 [102], 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) [103]. Randomized trials have shown that it is at least as effective as metronidazole, but not superior [103-107], and a single dose regimen appears to be as effective as vaginal clindamycin cream [108].

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 [109]. A single 1 gram oral dose of secnidazole appears to be as effective as the 2 gram dose [110].

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 [111,112]. 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 [30,113-119]. Cure rates with ampicillin and amoxicillin are mediocre.

Follow-up — Follow-up is unnecessary if symptoms resolve [40].

Sexual partners

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) [40,120]. However, the available trials are flawed; well-designed and larger trials should be performed to assess the efficacy of male partner treatment [121].

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 [30,34,122-125].

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 [25]). 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 [126]. 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 [92] and more than 50 percent experience a recurrence within 12 months [122]. 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 [12]. The only interventions proven to reduce development or recurrence of BV are chronic suppressive therapy and circumcision of male partners [127,128].

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 [40].

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 [34]. 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 [40]. 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 [127]. Secondary vaginal candidiasis was a common side effect.

Results can be improved by adding vaginal boric acid to the oral nitroimidazole induction therapy [129]. 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 [30,34,122-125]. 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 [123]. 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 [89,130]. 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 [34].

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 [81]. 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 [83,131-133].

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 [134-140].

Pregnant women

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 [141-146]. The therapeutic options include [40]:

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 [147], and the CDC no longer discourage the use of metronidazole in the first trimester [148]. 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 [149-151].

Asymptomatic infection and screening — As many as one-third of pregnant women in the United States have BV [61]. 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) [152]. The increased risk of preterm birth attributable to BV appears to be linked to preterm labor due to chorioamnionitis [62,153]. 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) [152].

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 [141,154,155], 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) [141]. 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 [154]. 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 [156] 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) [155]. 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 [40,154,157]. 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 [143,158-161]. 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 [162]. 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) [149-151]. However, in two studies, metronidazole use in pregnancy appeared to increase the risk of preterm birth [156,163]. 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 [155] 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 [164]. 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 [165]. 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 [166]. 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 [166].

In lactating women who are administered tinidazole, interruption of breastfeeding is recommended during treatment and for three days after the last dose [40].

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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 anerobic and highly specific fastidious BV-associated bacteria. Vaginal wall biofilms, comprised predominantly of Gardnerella vaginalis, appear to play a role in pathogenesis. (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.)

Diagnosis

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 containing 37.5 mg metronidazole) 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.

During therapy with metronidazole, alcohol should not be consumed. During therapy with clindamycin cream, latex condoms should not be used. (See 'Metronidazole' above and 'Clindamycin' above.)

We recommend not treating sexual partners of women with BV (Grade 1B). (See 'Sexual partners' above.)

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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REFERENCES

  1. Joesoef, M, Schmid, G. Bacterial vaginosis. In: Clinical evidence, BMJ Publishing Group, London 2001. p.887.
  2. Morris M, Nicoll A, Simms I, et al. Bacterial vaginosis: a public health review. BJOG 2001; 108:439.
  3. Tolosa JE, Chaithongwongwatthana S, Daly S, et al. The International Infections in Pregnancy (IIP) study: variations in the prevalence of bacterial vaginosis and distribution of morphotypes in vaginal smears among pregnant women. Am J Obstet Gynecol 2006; 195:1198.
  4. Allsworth JE, Peipert JF. Prevalence of bacterial vaginosis: 2001-2004 National Health and Nutrition Examination Survey data. Obstet Gynecol 2007; 109:114.
  5. Kenyon C, Colebunders R, Crucitti T. The global epidemiology of bacterial vaginosis: a systematic review. Am J Obstet Gynecol 2013; 209:505.
  6. Hill GB. The microbiology of bacterial vaginosis. Am J Obstet Gynecol 1993; 169:450.
  7. Ling Z, Kong J, Liu F, et al. Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis. BMC Genomics 2010; 11:488.
  8. Eschenbach DA, Davick PR, Williams BL, et al. Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis. J Clin Microbiol 1989; 27:251.
  9. Lamont RF, Sobel JD, Akins RA, et al. The vaginal microbiome: new information about genital tract flora using molecular based techniques. BJOG 2011; 118:533.
  10. Swidsinski A, Mendling W, Loening-Baucke V, et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol 2005; 106:1013.
  11. Swidsinski A, Doerffel Y, Loening-Baucke V, et al. Gardnerella biofilm involves females and males and is transmitted sexually. Gynecol Obstet Invest 2010; 70:256.
  12. Swidsinski A, Mendling W, Loening-Baucke V, et al. An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole. Am J Obstet Gynecol 2008; 198:97.e1.
  13. Alves P, Castro J, Sousa C, et al. Gardnerella vaginalis Outcompetes 29 Other Bacterial Species Isolated From Patients With Bacterial Vaginosis, Using in an In Vitro Biofilm Formation Model. J Infect Dis 2014; 210:593.
  14. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 2005; 353:1899.
  15. Fredricks DN, Fiedler TL, Thomas KK, et al. Targeted PCR for detection of vaginal bacteria associated with bacterial vaginosis. J Clin Microbiol 2007; 45:3270.
  16. Patterson JL, Stull-Lane A, Girerd PH, Jefferson KK. Analysis of adherence, biofilm formation and cytotoxicity suggests a greater virulence potential of Gardnerella vaginalis relative to other bacterial-vaginosis-associated anaerobes. Microbiology 2010; 156:392.
  17. Verstraelen H, Swidsinski A. The biofilm in bacterial vaginosis: implications for epidemiology, diagnosis and treatment. Curr Opin Infect Dis 2013; 26:86.
  18. Hymes SR, Randis TM, Sun TY, Ratner AJ. DNase inhibits Gardnerella vaginalis biofilms in vitro and in vivo. J Infect Dis 2013; 207:1491.
  19. Yen S, Shafer MA, Moncada J, et al. Bacterial vaginosis in sexually experienced and non-sexually experienced young women entering the military. Obstet Gynecol 2003; 102:927.
  20. Fethers KA, Fairley CK, Morton A, et al. Early sexual experiences and risk factors for bacterial vaginosis. J Infect Dis 2009; 200:1662.
  21. Fethers KA, Fairley CK, Hocking JS, et al. Sexual risk factors and bacterial vaginosis: a systematic review and meta-analysis. Clin Infect Dis 2008; 47:1426.
  22. Skinner CJ, Stokes J, Kirlew Y, et al. A case-controlled study of the sexual health needs of lesbians. Genitourin Med 1996; 72:277.
  23. Fethers K, Marks C, Mindel A, Estcourt CS. Sexually transmitted infections and risk behaviours in women who have sex with women. Sex Transm Infect 2000; 76:345.
  24. Marrazzo JM, Antonio M, Agnew K, Hillier SL. Distribution of genital Lactobacillus strains shared by female sex partners. J Infect Dis 2009; 199:680.
  25. Bradshaw CS, Walker SM, Vodstrcil LA, 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; 209:1562.
  26. Marrazzo JM, Koutsky LA, Eschenbach DA, et al. Characterization of vaginal flora and bacterial vaginosis in women who have sex with women. J Infect Dis 2002; 185:1307.
  27. Ness RB, Hillier SL, Richter HE, et al. Douching in relation to bacterial vaginosis, lactobacilli, and facultative bacteria in the vagina. Obstet Gynecol 2002; 100:765.
  28. Schwebke JR, Desmond RA, Oh MK. Predictors of bacterial vaginosis in adolescent women who douche. Sex Transm Dis 2004; 31:433.
  29. Ness RB, Kip KE, Soper DE, et al. Variability of bacterial vaginosis over 6- to 12-month intervals. Sex Transm Dis 2006; 33:381.
  30. 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; 44:213.
  31. Brotman RM, Klebanoff MA, Nansel TR, et al. A longitudinal study of vaginal douching and bacterial vaginosis--a marginal structural modeling analysis. Am J Epidemiol 2008; 168:188.
  32. Klebanoff MA, Nansel TR, Brotman RM, et al. Personal hygienic behaviors and bacterial vaginosis. Sex Transm Dis 2010; 37:94.
  33. Verstraelen H, Verhelst R, Nuytinck L, et al. Gene polymorphisms of Toll-like and related recognition receptors in relation to the vaginal carriage of Gardnerella vaginalis and Atopobium vaginae. J Reprod Immunol 2009; 79:163.
  34. Bradshaw CS, Vodstrcil LA, Hocking JS, et al. Recurrence of bacterial vaginosis is significantly associated with posttreatment sexual activities and hormonal contraceptive use. Clin Infect Dis 2013; 56:777.
  35. Amsel R, Totten PA, Spiegel CA, et al. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983; 74:14.
  36. Klebanoff MA, Schwebke JR, Zhang J, et al. Vulvovaginal symptoms in women with bacterial vaginosis. Obstet Gynecol 2004; 104:267.
  37. Livengood CH 3rd, Thomason JL, Hill GB. Bacterial vaginosis: diagnostic and pathogenetic findings during topical clindamycin therapy. Am J Obstet Gynecol 1990; 163:515.
  38. Sobel JD, Subramanian C, Foxman B, et al. Mixed vaginitis-more than coinfection and with therapeutic implications. Curr Infect Dis Rep 2013; 15:104.
  39. Marrazzo JM, Wiesenfeld HC, Murray PJ, et al. Risk factors for cervicitis among women with bacterial vaginosis. J Infect Dis 2006; 193:617.
  40. Workowski KA, Berman S, Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep 2010; 59:1.
  41. Sherrard J, Donders G, White D, et al. European (IUSTI/WHO) guideline on the management of vaginal discharge, 2011. Int J STD AIDS 2011; 22:421.
  42. Eschenbach DA, Hillier S, Critchlow C, et al. Diagnosis and clinical manifestations of bacterial vaginosis. Am J Obstet Gynecol 1988; 158:819.
  43. Landers DV, Wiesenfeld HC, Heine RP, et al. Predictive value of the clinical diagnosis of lower genital tract infection in women. Am J Obstet Gynecol 2004; 190:1004.
  44. 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; 29:297.
  45. Schwebke JR, Hillier SL, Sobel JD, et al. Validity of the vaginal gram stain for the diagnosis of bacterial vaginosis. Obstet Gynecol 1996; 88:573.
  46. Tam MT, Yungbluth M, Myles T. Gram stain method shows better sensitivity than clinical criteria for detection of bacterial vaginosis in surveillance of pregnant, low-income women in a clinical setting. Infect Dis Obstet Gynecol 1998; 6:204.
  47. Gratacós E, Figueras F, Barranco M, et al. Prevalence of bacterial vaginosis and correlation of clinical to Gram stain diagnostic criteria in low risk pregnant women. Eur J Epidemiol 1999; 15:913.
  48. Spiegel CA. Bacterial vaginosis. Clin Microbiol Rev 1991; 4:485.
  49. Greene JF 3rd, Kuehl TJ, Allen SR. The papanicolaou smear: inadequate screening test for bacterial vaginosis during pregnancy. Am J Obstet Gynecol 2000; 182:1048.
  50. Briselden AM, Hillier SL. Evaluation of affirm VP Microbial Identification Test for Gardnerella vaginalis and Trichomonas vaginalis. J Clin Microbiol 1994; 32:148.
  51. Sheiness D, Dix K, Watanabe S, Hillier SL. High levels of Gardnerella vaginalis detected with an oligonucleotide probe combined with elevated pH as a diagnostic indicator of bacterial vaginosis. J Clin Microbiol 1992; 30:642.
  52. Myziuk L, Romanowski B, Johnson SC. BVBlue test for diagnosis of bacterial vaginosis. J Clin Microbiol 2003; 41:1925.
  53. Sumeksri P, Koprasert C, Panichkul S. BVBLUE test for diagnosis of bacterial vaginosis in pregnant women attending antenatal care at Phramongkutklao Hospital. J Med Assoc Thai 2005; 88 Suppl 3:S7.
  54. Bradshaw CS, Morton AN, Garland SM, et al. Evaluation of a point-of-care test, BVBlue, and clinical and laboratory criteria for diagnosis of bacterial vaginosis. J Clin Microbiol 2005; 43:1304.
  55. Menard JP, Fenollar F, Henry M, et al. Molecular quantification of Gardnerella vaginalis and Atopobium vaginae loads to predict bacterial vaginosis. Clin Infect Dis 2008; 47:33.
  56. Cartwright CP, Lembke BD, Ramachandran K, et al. Development and validation of a semiquantitative, multitarget PCR assay for diagnosis of bacterial vaginosis. J Clin Microbiol 2012; 50:2321.
  57. Menard JP, Mazouni C, Fenollar F, et al. Diagnostic accuracy of quantitative real-time PCR assay versus clinical and Gram stain identification of bacterial vaginosis. Eur J Clin Microbiol Infect Dis 2010; 29:1547.
  58. Dumonceaux TJ, Schellenberg J, Goleski V, et al. Multiplex detection of bacteria associated with normal microbiota and with bacterial vaginosis in vaginal swabs by use of oligonucleotide-coupled fluorescent microspheres. J Clin Microbiol 2009; 47:4067.
  59. Huppert JS, Hesse EA, Bernard MC, et al. Accuracy and trust of self-testing for bacterial vaginosis. J Adolesc Health 2012; 51:400.
  60. Singh RH, Zenilman JM, Brown KM, et al. The role of physical examination in diagnosing common causes of vaginitis: a prospective study. Sex Transm Infect 2013; 89:185.
  61. 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; 192:470.
  62. Eschenbach DA. Bacterial vaginosis: emphasis on upper genital tract complications. Obstet Gynecol Clin North Am 1989; 16:593.
  63. Flynn CA, Helwig AL, Meurer LN. Bacterial vaginosis in pregnancy and the risk of prematurity: a meta-analysis. J Fam Pract 1999; 48:885.
  64. Hauth JC, Macpherson C, Carey JC, et al. Early pregnancy threshold vaginal pH and Gram stain scores predictive of subsequent preterm birth in asymptomatic women. Am J Obstet Gynecol 2003; 188:831.
  65. Andrews WW, Hauth JC, Cliver SP, et al. Association of asymptomatic bacterial vaginosis with endometrial microbial colonization and plasma cell endometritis in nonpregnant women. Am J Obstet Gynecol 2006; 195:1611.
  66. Oleen-Burkey MA, Hillier SL. Pregnancy complications associated with bacterial vaginosis and their estimated costs. Infect Dis Obstet Gynecol 1995; 3:149.
  67. MacDermott RI. Bacterial vaginosis. Br J Obstet Gynaecol 1995; 102:92.
  68. 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; 180:1863.
  69. Myer L, Denny L, Telerant R, et al. Bacterial vaginosis and susceptibility to HIV infection in South African women: a nested case-control study. J Infect Dis 2005; 192:1372.
  70. Cohen CR, Lingappa JR, Baeten JM, 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:e1001251.
  71. Cherpes TL, Meyn LA, Krohn MA, et al. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Infect Dis 2003; 37:319.
  72. Wiesenfeld HC, Hillier SL, Krohn MA, et al. Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis 2003; 36:663.
  73. Balkus JE, Richardson BA, Rabe LK, et al. Bacterial vaginosis and the risk of trichomonas vaginalis acquisition among HIV-1-negative women. Sex Transm Dis 2014; 41:123.
  74. Taylor BD, Darville T, Haggerty CL. Does bacterial vaginosis cause pelvic inflammatory disease? Sex Transm Dis 2013; 40:117.
  75. Ness RB, Hillier SL, Kip KE, et al. Bacterial vaginosis and risk of pelvic inflammatory disease. Obstet Gynecol 2004; 104:761.
  76. Gillet E, Meys JF, Verstraelen H, et al. Association between bacterial vaginosis and cervical intraepithelial neoplasia: systematic review and meta-analysis. PLoS One 2012; 7:e45201.
  77. Guo YL, You K, Qiao J, et al. Bacterial vaginosis is conducive to the persistence of HPV infection. Int J STD AIDS 2012; 23:581.
  78. King CC, Jamieson DJ, Wiener J, et al. Bacterial vaginosis and the natural history of human papillomavirus. Infect Dis Obstet Gynecol 2011; 2011:319460.
  79. Klebanoff MA, Hauth JC, MacPherson CA, et al. Time course of the regression of asymptomatic bacterial vaginosis in pregnancy with and without treatment. Am J Obstet Gynecol 2004; 190:363.
  80. Hay PE, Morgan DJ, Ison CA, et al. A longitudinal study of bacterial vaginosis during pregnancy. Br J Obstet Gynaecol 1994; 101:1048.
  81. Schwebke JR. Asymptomatic bacterial vaginosis: response to therapy. Am J Obstet Gynecol 2000; 183:1434.
  82. Hillier SL, Lipinski C, Briselden AM, Eschenbach DA. Efficacy of intravaginal 0.75% metronidazole gel for the treatment of bacterial vaginosis. Obstet Gynecol 1993; 81:963.
  83. Schwebke JR, Desmond R. A randomized trial of metronidazole in asymptomatic bacterial vaginosis to prevent the acquisition of sexually transmitted diseases. Am J Obstet Gynecol 2007; 196:517.e1.
  84. European (International Union against Sexually Transmitted Infections [IUSTI]/World Health Organization [WHO]) Guideline on the Management of Vaginal Discharge. 2011
  85. UK national guideline for the management of bacterial vaginosis 2012
  86. National guideline for the management of bacterial vaginosis. Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). Sex Transm Infect 1999; 75 Suppl 1:S16.
  87. Joesoef MR, Schmid GP, Hillier SL. Bacterial vaginosis: review of treatment options and potential clinical indications for therapy. Clin Infect Dis 1999; 28 Suppl 1:S57.
  88. Greaves WL, Chungafung J, Morris B, et al. Clindamycin versus metronidazole in the treatment of bacterial vaginosis. Obstet Gynecol 1988; 72:799.
  89. Oduyebo OO, Anorlu RI, Ogunsola FT. The effects of antimicrobial therapy on bacterial vaginosis in non-pregnant women. Cochrane Database Syst Rev 2009; :CD006055.
  90. Koumans EH, Markowitz LE, Hogan V, CDC BV Working Group. Indications for therapy and treatment recommendations for bacterial vaginosis in nonpregnant and pregnant women: a synthesis of data. Clin Infect Dis 2002; 35:S152.
  91. Swedberg J, Steiner JF, Deiss F, et al. Comparison of single-dose vs one-week course of metronidazole for symptomatic bacterial vaginosis. JAMA 1985; 254:1046.
  92. Hillier, S, Holmes, KK. Bacterial vaginosis. In: Holmes, KK, Mardh, PA, Sparling, PF, Wiesner, PJ (Eds), Sexually Transmitted Diseases, 2nd ed, McGraw-Hill, New York: 1990, p. 547.
  93. Ferris DG, Litaker MS, Woodward L, et al. Treatment of bacterial vaginosis: a comparison of oral metronidazole, metronidazole vaginal gel, and clindamycin vaginal cream. J Fam Pract 1995; 41:443.
  94. Hanson JM, McGregor JA, Hillier SL, et al. Metronidazole for bacterial vaginosis. A comparison of vaginal gel vs. oral therapy. J Reprod Med 2000; 45:889.
  95. Joesoef MR, Schmid GP. Bacterial vaginosis: review of treatment options and potential clinical indications for therapy. Clin Infect Dis 1995; 20 Suppl 1:S72.
  96. Bro F. Metronidazole pessaries compared with placebo in the treatment of bacterial vaginosis. Scand J Prim Health Care 1990; 8:219.
  97. Livengood CH 3rd, Soper DE, Sheehan KL, et al. Comparison of once-daily and twice-daily dosing of 0.75% metronidazole gel in the treatment of bacterial vaginosis. Sex Transm Dis 1999; 26:137.
  98. Ransom SB, McComish JF, Greenberg R, Tolford DA. Oral metronidazole vs. Metrogel Vaginal for treating bacterial vaginosis. Cost-effectiveness evaluation. J Reprod Med 1999; 44:359.
  99. Kurohara ML, Kwong FK, Lebherz TB, Klaustermeyer WB. Metronidazole hypersensitivity and oral desensitization. J Allergy Clin Immunol 1991; 88:279.
  100. Paavonen J, Mangioni C, Martin MA, Wajszczuk CP. Vaginal clindamycin and oral metronidazole for bacterial vaginosis: a randomized trial. Obstet Gynecol 2000; 96:256.
  101. Beigi RH, Austin MN, Meyn LA, et al. Antimicrobial resistance associated with the treatment of bacterial vaginosis. Am J Obstet Gynecol 2004; 191:1124.
  102. Tinidazole (Tindamax)--a new option for treatment of bacterial vaginosis. Med Lett Drugs Ther 2007; 49:73.
  103. Ekgren J, Norling BK, Degre M, Midtvedt T. Comparison of tinidazole given as a single dose and on 2 consecutive days for the treatment of nonspecific bacterial vaginosis. Gynecol Obstet Invest 1988; 26:313.
  104. Livengood CH 3rd, Ferris DG, Wiesenfeld HC, et al. Effectiveness of two tinidazole regimens in treatment of bacterial vaginosis: a randomized controlled trial. Obstet Gynecol 2007; 110:302.
  105. Schindler EM, Thamm H, Ansmann EB, et al. [Treatment of bacterial vaginitis. Multicenter, randomized, open study with tinidazole in comparison with metronidazole]. Fortschr Med 1991; 109:138.
  106. Prakash AT, Sharma LK, Pandit PN. Primary carcinoma of the gallbladder. Br J Surg 1975; 62:33.
  107. Schwebke JR, Desmond RA. Tinidazole vs metronidazole for the treatment of bacterial vaginosis. Am J Obstet Gynecol 2011; 204:211.e1.
  108. Milani M, Barcellona E, Agnello A. Efficacy of the combination of 2 g oral tinidazole and acidic buffering vaginal gel in comparison with vaginal clindamycin alone in bacterial vaginosis: a randomized, investigator-blinded, controlled trial. Eur J Obstet Gynecol Reprod Biol 2003; 109:67.
  109. Bohbot JM, Vicaut E, Fagnen D, Brauman M. Treatment of bacterial vaginosis: a multicenter, double-blind, double-dummy, randomised phase III study comparing secnidazole and metronidazole. Infect Dis Obstet Gynecol 2010; 2010.
  110. Núñez JT, Gómez G. Low-dose secnidazole in the treatment of bacterial vaginosis. Int J Gynaecol Obstet 2005; 88:281.
  111. Senok AC, Verstraelen H, Temmerman M, Botta GA. Probiotics for the treatment of bacterial vaginosis. Cochrane Database Syst Rev 2009; :CD006289.
  112. Falagas M, Betsi GI, Athanasiou S. Probiotics for the treatment of women with bacterial vaginosis. Clin Microbiol Infect 2007; 13:657.
  113. McCormack WM, Covino JM, Thomason JL, et al. Comparison of clindamycin phosphate vaginal cream with triple sulfonamide vaginal cream in the treatment of bacterial vaginosis. Sex Transm Dis 2001; 28:569.
  114. Wathne B, Holst E, Hovelius B, Mårdh PA. Erythromycin versus metronidazole in the treatment of bacterial vaginosis. Acta Obstet Gynecol Scand 1993; 72:470.
  115. Piot P. Bacterial vaginosis. An evaluation of treatment. Scand J Urol Nephrol Suppl 1984; 86:229.
  116. Wewalka G, Stary A, Bosse B, et al. Efficacy of povidone-iodine vaginal suppositories in the treatment of bacterial vaginosis. Dermatology 2002; 204 Suppl 1:79.
  117. Duff P, Lee ML, Hillier SL, et al. Amoxicillin treatment of bacterial vaginosis during pregnancy. Obstet Gynecol 1991; 77:431.
  118. Schoeman J, Steyn PS, Odendaal HJ, Grové D. Bacterial vaginosis diagnosed at the first antenatal visit better predicts preterm labour than diagnosis later in pregnancy. J Obstet Gynaecol 2005; 25:751.
  119. Verstraelen H, Verhelst R, Roelens K, Temmerman M. Antiseptics and disinfectants for the treatment of bacterial vaginosis: a systematic review. BMC Infect Dis 2012; 12:148.
  120. Potter J. Should sexual partners of women with bacterial vaginosis receive treatment? Br J Gen Pract 1999; 49:913.
  121. Mehta SD. Systematic review of randomized trials of treatment of male sexual partners for improved bacteria vaginosis outcomes in women. Sex Transm Dis 2012; 39:822.
  122. Bradshaw CS, Morton AN, Hocking J, 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; 193:1478.
  123. Sanchez S, Garcia PJ, Thomas KK, et al. Intravaginal metronidazole gel versus metronidazole plus nystatin ovules for bacterial vaginosis: a randomized controlled trial. Am J Obstet Gynecol 2004; 191:1898.
  124. Schwebke JR, Desmond R. Risk factors for bacterial vaginosis in women at high risk for sexually transmitted diseases. Sex Transm Dis 2005; 32:654.
  125. Smart S, Singal A, Mindel A. Social and sexual risk factors for bacterial vaginosis. Sex Transm Infect 2004; 80:58.
  126. Marrazzo JM, Thomas KK, Ringwood K. A behavioural intervention to reduce persistence of bacterial vaginosis among women who report sex with women: results of a randomised trial. Sex Transm Infect 2011; 87:399.
  127. 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; 194:1283.
  128. Gray RH, Kigozi G, Serwadda D, et al. The effects of male circumcision on female partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda. Am J Obstet Gynecol 2009; 200:42.e1.
  129. Reichman O, Akins R, Sobel JD. Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis. Sex Transm Dis 2009; 36:732.
  130. Anukam K, Osazuwa E, Ahonkhai I, et al. Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial. Microbes Infect 2006; 8:1450.
  131. Wawer MJ, Sewankambo NK, Serwadda D, et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet 1999; 353:525.
  132. Grosskurth H, Mosha F, Todd J, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 1995; 346:530.
  133. Moreira C, Venkatesh KK, DeLong A, et al. Effect of treatment of asymptomatic bacterial vaginosis on HIV-1 shedding in the genital tract among women on antiretroviral therapy: a pilot study. Clin Infect Dis 2009; 49:991.
  134. Penney GC, Thomson M, Norman J, et al. A randomised comparison of strategies for reducing infective complications of induced abortion. Br J Obstet Gynaecol 1998; 105:599.
  135. Larsson PG, Platz-Christensen JJ, Dalaker K, et al. Treatment with 2% clindamycin vaginal cream prior to first trimester surgical abortion to reduce signs of postoperative infection: a prospective, double-blinded, placebo-controlled, multicenter study. Acta Obstet Gynecol Scand 2000; 79:390.
  136. Miller L, Thomas K, Hughes JP, et al. Randomised treatment trial of bacterial vaginosis to prevent post-abortion complication. BJOG 2004; 111:982.
  137. Crowley T, Low N, Turner A, et al. Antibiotic prophylaxis to prevent post-abortal upper genital tract infection in women with bacterial vaginosis: randomised controlled trial. BJOG 2001; 108:396.
  138. Larsson PG, Platz-Christensen JJ, Thejls H, et al. Incidence of pelvic inflammatory disease after first-trimester legal abortion in women with bacterial vaginosis after treatment with metronidazole: a double-blind, randomized study. Am J Obstet Gynecol 1992; 166:100.
  139. Larsson PG, Carlsson B. Does pre- and postoperative metronidazole treatment lower vaginal cuff infection rate after abdominal hysterectomy among women with bacterial vaginosis? Infect Dis Obstet Gynecol 2002; 10:133.
  140. ACOG Committee on Practice Bulletins--Gynecology. ACOG practice bulletin No. 104: antibiotic prophylaxis for gynecologic procedures. Obstet Gynecol 2009; 113:1180.
  141. Brocklehurst P, Gordon A, Heatley E, Milan SJ. Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev 2013; 1:CD000262.
  142. Leitich H, Brunbauer M, Bodner-Adler B, et al. Antibiotic treatment of bacterial vaginosis in pregnancy: a meta-analysis. Am J Obstet Gynecol 2003; 188:752.
  143. Okun N, Gronau KA, Hannah ME. Antibiotics for bacterial vaginosis or Trichomonas vaginalis in pregnancy: a systematic review. Obstet Gynecol 2005; 105:857.
  144. Guise JM, Mahon SM, Aickin M, et al. Screening for bacterial vaginosis in pregnancy. Am J Prev Med 2001; 20:62.
  145. Riggs MA, Klebanoff MA. Treatment of vaginal infections to prevent preterm birth: a meta-analysis. Clin Obstet Gynecol 2004; 47:796.
  146. Joesoef MR, Hillier SL, Wiknjosastro G, et al. Intravaginal clindamycin treatment for bacterial vaginosis: effects on preterm delivery and low birth weight. Am J Obstet Gynecol 1995; 173:1527.
  147. Caro-Patón T, Carvajal A, Martin de Diego I, et al. Is metronidazole teratogenic? A meta-analysis. Br J Clin Pharmacol 1997; 44:179.
  148. Centers for Disease Control and Prevention, Workowsk,i KA, Berman, SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep 2006; 55(RR-11):1.
  149. McDonald HM, O'Loughlin JA, Vigneswaran R, et al. Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial. Br J Obstet Gynaecol 1997; 104:1391.
  150. 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; 171:345.
  151. Hauth JC, Goldenberg RL, Andrews WW, et al. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N Engl J Med 1995; 333:1732.
  152. Leitich H, Kiss H. Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol 2007; 21:375.
  153. Hillier SL, Martius J, Krohn M, et al. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. N Engl J Med 1988; 319:972.
  154. Nygren P, Fu R, Freeman M, et al. Evidence on the benefits and harms of screening and treating pregnant women who are asymptomatic for bacterial vaginosis: an update review for the U.S. Preventive Services Task Force. Ann Intern Med 2008; 148:220.
  155. Lamont RF, Nhan-Chang CL, Sobel JD, et al. Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis. Am J Obstet Gynecol 2011; 205:177.
  156. Odendaal HJ, Popov I, Schoeman J, et al. Preterm labour--is bacterial vaginosis involved? S Afr Med J 2002; 92:231.
  157. Committee on Practice Bulletins—Obstetrics, The American College of Obstetricians and Gynecologists. Practice bulletin no. 130: prediction and prevention of preterm birth. Obstet Gynecol 2012; 120:964.
  158. Leitich H, Bodner-Adler B, Brunbauer M, et al. Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis. Am J Obstet Gynecol 2003; 189:139.
  159. U.S. Preventive Services Task Force. Screening for bacterial vaginosis in pregnancy to prevent preterm delivery: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008; 148:214.
  160. Ugwumadu A, Manyonda I, Reid F, Hay P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial. Lancet 2003; 361:983.
  161. Lamont RF, Duncan SL, Mandal D, Bassett P. Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora. Obstet Gynecol 2003; 101:516.
  162. Macones GA, Parry S, Elkousy M, et al. A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth. Am J Obstet Gynecol 2004; 190:1504.
  163. Klebanoff MA, Carey JC, Hauth JC, et al. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med 2001; 345:487.
  164. Vermeulen GM, Bruinse HW. Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double-blind trial. Br J Obstet Gynaecol 1999; 106:652.
  165. LactMed available at http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~R2NQWq:1 (Accessed on January 19, 2010).
  166. Lactmed. Available at http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~R2NQWq:2. (Accessed on January 19, 2010).
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