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تعداد ایتم قابل مشاهده باقیمانده : 4 مورد

Bacterial vaginosis: Treatment

Bacterial vaginosis: Treatment
Author:
Jack D Sobel, MD
Section Editor:
Robert L Barbieri, MD
Deputy Editor:
Kristen Eckler, MD, FACOG
Literature review current through: Aug 2021. | This topic last updated: Jul 09, 2021.

INTRODUCTION — Bacterial vaginosis (BV) is the most common cause of abnormal vaginal discharge in reproductive-age females. Treatment is aimed at relieving symptoms, although many individuals are asymptomatic. Of those with symptoms, abnormal vaginal discharge and fishy odor are typical.

This topic will present the treatment options for various groups of patients with BV. Related topics on the presentation and diagnosis of BV, the approach to the individual with vaginitis, and cervicitis are presented separately.

(See "Bacterial vaginosis: Clinical manifestations and diagnosis".)

(See "Approach to females with symptoms of vaginitis".)

(See "Acute cervicitis".)

In this topic, when discussing study results, we will use the terms "women" or "patients" as they are used in the studies presented. However, we recognize that not all genetic females identify as women, and we encourage the reader to consider the specific counseling and treatment needs of transgender and gender diverse individuals.

GOALS OF TREATMENT — Goals of treatment include:

Relief of symptoms (if present). (See "Bacterial vaginosis: Clinical manifestations and diagnosis", section on 'Clinical features'.)

Reduction of postoperative infection – For individuals with asymptomatic infection prior to surgical abortion or hysterectomy, treatment can reduce the risk of postoperative infection. (See 'Individuals undergoing gynecologic procedures' below.)

Reduction of sexually transmitted infections – Treatment of BV may reduce the risk of acquiring sexually transmitted infections (STIs), including HIV [1,2]. For this reason, some experts support the concept of treating all patients with BV regardless of presence or absence of symptoms. However, we agree with recommendations to not treat asymptomatic individuals who are not pregnant [3,4]. Asymptomatic pregnant individuals with previous preterm births may benefit from treatment, but screening and treatment of these individuals are controversial. (See 'Pregnant persons' below.)

Without treatment, BV resolves spontaneously in up to one-third of nonpregnant and one-half of pregnant individuals [5-8].

NONPREGNANT SYMPTOMATIC FEMALES

Preferred treatments — The following treatment recommendations are consistent with those of the Centers for Disease Control and Prevention (CDC) (algorithm 1) [3]. Guidelines from other organizations are available elsewhere [9,10].

Treatment selection — Both metronidazole and clindamycin, as oral or vaginal formulations, are preferred therapies and have similar treatment efficacy (algorithm 1). The choice of medication is based on availability, patient preference, side effects, cost, and history of response or adverse reactions [11]. Oral metronidazole is commonly used because oral formulations are often preferred by patients rather than vaginal ones, and metronidazole is less commonly associated with Clostridioides difficile infection compared with clindamycin [12].

Oral verus vaginal medicationMetronidazole and clindamycin are both available as oral and vaginal formulations. Many patients consider oral medication to be more convenient than vaginal dosing, but oral medication causes more systemic side effects, such as headache, nausea, abdominal pain, and Clostridioides (formerly Clostridium) difficile associated diarrhea.

Alternative oral treatment options – If neither metronidazole nor clindamycin are available, either tinidazole or secnidazole are reasonable oral alternatives. While efficacy appears to be similar to metronidazole and clindamycin, cost and availability are more likely to be prohibitive. No new drugs have been introduced for BV therapy in the past decade. (See 'Alternative drugs' below.)

Metronidazole — Metronidazole is given as an oral or vaginal medication over multiple days (table 1 and algorithm 1).

Dosing – The choice of oral versus vaginal therapy depends upon patient preference because the efficacy is similar for multiday oral or vaginal treatments.

Oral pills – We suggest oral metronidazole 500 mg twice daily for seven days [3]. Treatment with a single oral dose of 2 grams of metronidazole has lower efficacy [13] and thus is no longer recommended for treatment of BV [3].

Vaginal gel – Vaginal therapy is given as metronidazole 0.75% gel; a 5-gram applicator is inserted into the vagina once daily for five days (5 grams of gel contains 37.5 mg of metronidazole) [3,14,15]. A newer single-dose metronidazole gel (1.3%) is under investigation [16].

The multiday vaginal gel has similar efficacy to seven days of oral metronidazole [17-19]. While the single-dose 1.3% treatment is superior to placebo gel [16], it is not known if the 1.3% single-day dose is as efficacious as the multiday oral or multiday 0.75% vaginal treatments, and therefore we prefer the multiday treatments.

Adverse effects

Common – Side effects of metronidazole (oral or vaginal) include a metallic taste, nausea (in 10 percent of patients), transient neutropenia (7.5 percent), prolongation of international normalized ratio in patients taking vitamin K antagonists (eg, warfarin), and peripheral neuropathy [20]. Gastrointestinal side effects are less common with vaginal administration [18]. Patients who are being treated with disulfiram should not use metronidazole as psychotic reactions have been reported [20].

Alcohol consumption – For patients receiving oral nitroimidazoles, manufacturer packaging advises abstaining from alcohol consumption during treatment and for 24 hours after treatment [20]. However, data supporting this statement are sparse, and the magnitude of risk appears to be low [21]. We do not counsel patients taking oral or vaginal metronidazole to avoid alcohol during treatment.

Drug allergy – Allergy to metronidazole is uncommon; it manifests as rash, urticaria, pruritus, and, rarely, anaphylaxis, which can be successfully treated by oral desensitization [22].

Efficacy – The efficacy of metronidazole has been established in randomized trials using either placebo or active drug controls [23,24]. Published cure rates can 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.

Multiday therapy – Treatment of symptomatic nonpregnant patients with multiday metronidazole administered either orally (seven days) or intravaginally (five days) results in a high rate of clinical cure (70 to 80 percent at four weeks of follow-up) [11,23,25-27]. 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 up to 80 percent [17,18,23,26,28-30].

Longer course treatment – There is little evidence of benefit from prolonging therapy longer than seven days. Although early cure rates are significantly higher when the initial course of metronidazole therapy is 14 rather than 7 days, long-term cure rates (21 days after completion of therapy) are similar for both treatment regimens [31].

Clindamycin — When selected for treatment of BV, clindamycin is typically given as a vaginal cream for seven nights (table 1 and algorithm 1) [3]. While oral clindamycin is an alternative treatment option, it is less preferred because of potential risk of Clostridioides (formerly Clostridium) difficile-associated diarrhea [12].

Dosing

Preferred – The preferred regimen is clindamycin cream 2% given vaginally as 5 grams of cream daily for seven days (5 grams of cream contains 100 mg of clindamycin phosphate) [3].

Alternative regimens – Alternative regimens include [3,32]:

-Clindamycin 300 mg twice daily orally for seven days.

or

-Clindamycin 100 mg vaginal suppositories at bedtime for three days.

or

-Clindamycin bioadhesive cream (Clindesse) 2% as a single vaginal dose of 5 grams of cream containing 100 mg of clindamycin phosphate.

Adverse effects

Common – The most common adverse effects are vulvovaginal candidiasis (topical and oral formulations) and gastrointestinal side effects (oral formulation) [33,34]. Although uncommon, pseudomembranous colitis has been reported with both formulations.

Clindamycin resistance – Intravaginal clindamycin therapy has been associated with an increased prevalence of clindamycin-resistant anaerobic bacteria in the vagina post-treatment (17 percent of bacterial isolates before versus 53 percent of isolates after therapy) [35]. This effect persisted in most women for at least 90 days after clindamycin treatment. Further investigation is required to determine the clinical implications of these findings.

Impact on latex condomsClindamycin cream should not be used concurrently with latex condoms, which may be weakened.

Efficacy – The efficacy of oral and vaginal clindamycin preparations have been demonstrated in a meta-analysis of randomized trials, both comparative and placebo-controlled [23].

Alternative drugs — Oral tinidazole and secnidazole have demonstrated efficacy similar to that of oral metronidazole and may be more convenient as they have five- and one-day dosing, respectively. However, as they are higher cost, they are considered alternatives to the treatments above.

Tinidazole — Tinidazole is a second-generation nitroimidazole that is considered an alternative regimen if metronidazole and clindamycin are unavailable or not tolerated [3]. It has a longer half-life than metronidazole (12 to 14 hours versus 6 to 7 hours) and fewer side effects reported in some, but not all, studies [36].

Dose – 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) [37].

Adverse effects – In initial clinical trials with variable designs and treatment indications, 11 percent of patients reported adverse effects with a single 2-gram dose of tinidazole [38]. The most common were a metallic/bitter taste (3.7 percent), nausea (3.2 percent), and weakness or fatigue (2.1 percent).

Efficacy – Randomized trials have shown that it is at least as effective as metronidazole, but not superior [37,39-41], and a single-dose regimen appears to be as effective as vaginal clindamycin cream [42].

Secnidazole — Secnidazole is a nitroimidazole antibiotic with a longer half-life than metronidazole (approximately 17 hours versus 8 hours) [43].

DoseSecnidazole is prescribed as a single 2-gram packet of granules that are taken once orally, typically mixed into a soft food (ie, applesauce, yogurt, or pudding) [44]. The mixture should be consumed within 30 minutes, and the granules should not be crunched or chewed.

Adverse effects – Compared with placebo, treatment with secnidazole is more likely to result in vulvovaginal candidiasis (nearly 9.6 percent), headache (3.6 percent), nausea (3.6 percent), diarrhea (2.5 percent), and abdominal pain (2 percent) [44].

Efficacy – In a phase 3 trial comparing a single 2-gram dose of oral secnidazole with placebo, single-dose secnidazole was superior to placebo, with clinical outcome responder rates of 53 versus 19 percent [43]. A single 1-gram oral dose of secnidazole appears to be effective as well [45,46]. Although compliance is enhanced by the convenience of a single-dose regimen, there is no evidence demonstrating that single-dose secnidazole is superior to multidose metronidazole therapy, which typically is much less expensive. While previously available in other countries, secnidazole was approved for the treatment of BV by the US Food and Drug Administration (FDA) in 2017 [44].

Role of probiotics — Probiotics (live microorganisms that 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 [47,48]. Although some trials have reported very promising results, particularly for treatment with an L. crispatus strain, we feel the results should be reproduced in more well-designed and larger trials before use of this therapy is considered [49]. 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. The regulatory oversight and quality of commercially available probiotics vary worldwide. In the United States, the content of these products is not standardized and often of poor quality. The FDA advises caution in using dietary supplements containing live bacteria or yeast in immunocompromised patients as patient death has been reported [50].

Less effective and ineffective therapies — Triple-sulfa creams, erythromycin, tetracycline, ampicillin, amoxicillin, lactic acid gel, acetic acid gel, ascorbic acid, azithromycin, chlorhexidine, hydrogen peroxide, vaginal boric acid as an isolated therapy, and povidone-iodine vaginal douches are significantly less effective than metronidazole and clindamycin and should not be used [31,51-57]. Cure rates with ampicillin and amoxicillin are mediocre. Boric acid has not been shown to be effective in treating isolated or initial cases of BV. While boric acid may play a supportive role in treatment with primary antibiotic therapy, it is not to be used for primary treatment. There is a role for boric acid vaginal suppositories in patients with relapsing or recurrent BV when used in combination with antimicrobial agents. A novel form of boric acid is under investigation [58]. (See 'Relapse and recurrent infection' below.)

Follow-up — Follow-up is unnecessary if symptoms resolve [3].

NONPREGNANT ASYMPTOMATIC FEMALES — We suggest observation, and not antibiotic treatment, for asymptomatic non-pregnant individuals [3,4]. 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. Although some experts recommend treatment of asymptomatic BV because affected individuals are more susceptible to acquiring other sexually transmitted infections (STIs, including HIV and herpes simplex virus), available evidence is insufficient to clearly support or exclude a benefit of treatment [59-63].

Evidence – 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 [7]. 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.

Exception – For individuals undergoing gynecologic procedures or surgery that involved the vagina, treatment of BV has been associated with reduced risk of postoperative infection [63]. (See 'Individuals undergoing gynecologic procedures' below.)

PREGNANT PERSONS

Symptomatic — Pregnant individuals with symptomatic BV are treated to relieve bothersome symptoms. In a meta-analysis of 10 trials comparing antibiotic therapy with placebo for individuals with confirmed BV or intermediate bacterial flora while pregnant, antibiotic therapy effectively reduced BV during pregnancy (average risk ratio 0.42, 95% CI 0.31-0.56, 10 trials, 4403 women) [64]. While oral and vaginal regimens are available, oral metronidazole is commonly used as some data indicate greater efficacy of oral metronidazole against upper tract infection compared with other options [65-67].

Oral treatment regimens – Oral treatment is effective and has not been associated with adverse fetal or obstetric effects [64,68-72]. Therapeutic options include [3]:

Metronidazole 500 mg orally twice daily for seven days

or

Metronidazole 250 mg orally three times daily for seven days

or

Clindamycin 300 mg orally twice daily for seven days

Role of topical therapy – The author and other experts prefer oral therapy in pregnant patients because some data indicate oral treatment is more effective against potential subclinical upper genital tract infection [65-67]. However, as topical therapy is not inferior to oral therapy in effecting cure or preventing adverse pregnancy outcomes such as preterm birth, the Centers for Disease Control and Prevention (CDC) recommend either oral or topical therapy for treatment of symptomatic pregnant individuals [3]. The regimens are the same as for nonpregnant patients. (See 'Preferred treatments' above.)

Safety – 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 congenital anomalies [73], and the CDC no longer discourages the use of metronidazole in the first trimester [3]. An additional concern is that the drug is mutagenic in bacteria and carcinogenic in mice, but there is no evidence of harm in humans.

Asymptomatic infection and screening — Asymptomatic pregnant individuals with previous preterm births may benefit from treatment, but screening and treatment of these individuals are controversial as the available data do not show a consistent benefit to this approach.

Our approach – Based upon the data below, we and others, including the American College of Obstetricians and Gynecologists (ACOG), United States Preventive Services Task Force (USPSTF), CDC, and Society of Obstetricians and Gynaecologists of Canada, suggest not routinely screening and treating all pregnant individuals with asymptomatic BV to prevent preterm birth and its consequences [3,74-77]. It is not possible to define specific features characterizing a subgroup of individuals who might respond favorably to a screening and treatment protocol. Defining these features is an active area of investigation.

However, as illustrated below, there may be benefits to early screening and treatment of asymptomatic pregnant individuals who have a history of a previous preterm delivery, but there are insufficient data to recommend this as a routine practice [69,78-81]. Further definition of high-risk subgroups is under investigation. As an example, individuals with polymorphisms of genes regulating cytokine production (eg, tumor necrosis factor variants) have a greater proinflammatory immune response to infectious stimuli, such as BV [82]. Enhanced induction of cytokines in these individuals could then lead to preterm labor or rupture of membranes. Other aspects of host response (eg, low levels of immunoglobulin A [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 individuals with BV at high risk of preterm birth. Additional information is available in related content:

(See "Preterm birth: Risk factors, interventions for risk reduction, and maternal prognosis", section on 'Genetic factors'.)

(See "Preterm birth: Risk factors, interventions for risk reduction, and maternal prognosis", section on 'Genital tract infection/colonization'.)

Risk for adverse pregnancy outcomes, including preterm birth – As many as one-third of pregnant individuals in the United States have BV [83]. 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) [84]. The increased risk of preterm birth attributable to BV appears to be linked to preterm labor due to chorioamnionitis [85,86]. Other complications of BV include postpartum endometritis (odds ratio [OR] 2.53, 95% CI 1.25-5.08), and an increased risk of late miscarriage (OR 6.32, 95% CI 3.65-10.90) [84].

Conflicting data for screening and treatment – Despite the association between BV and adverse outcome, screening and treatment of asymptomatic BV during pregnancy are controversial and vary in part based on the individual's baseline risk for preterm delivery [77]. 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 obstetric population [64,74,87], 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. Examples include:

In a 2015 Cochrane meta-analysis of eight trials comparing the use of prophylactic antibiotics in the second or third trimester of pregnancy in women at risk for preterm delivery, antibiotic treatment reduced preterm delivery in the subgroup of women with a prior preterm delivery and current BV compared with no treatment (risk ratio 0.64, 95% CI 0.47-0.88, one trial, 258 women) [88]. Antibiotic prophylaxis did not reduce preterm delivery in women with a prior history of preterm birth who did not have BV.

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) [64]. 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, three trials, 421 women).

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 out of 1183] versus 6.2 percent [72 out of 1163]; fixed effects relative risk [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 out of 639] versus 1.9 percent [12 out of 631]; RR 0.20, 95% CI 0.05-0.76) [87]. 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.

Treatment regimens – When the decision is made to treat asymptomatic pregnant individuals who have confirmed BV, the optimal choice of antibiotic, timing of therapy, duration of use, and harms of therapy are debated. Based on the data presented below, we use oral therapy when treatment is indicated and consider both metronidazole and clindamycin acceptable choices.

Metronidazole – The first trials demonstrated a reduction in preterm birth in high-risk women treated with oral metronidazole or oral metronidazole and erythromycin (table 2) [65-67]. However, in two studies, metronidazole use in pregnancy appeared to increase the risk of preterm birth [89,90]. This association requires further investigation and confirmation before avoiding metronidazole for treatment of BV in pregnancy.

Clindamycin – Trials suggest that oral clindamycin given early in pregnancy is an effective therapy [87]. 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 [91].

LACTATING (BREASTFEEDING) INDIVIDUALS

Our approach

Metronidazole (preferred) – Our preferred treatment for lactating individuals is oral metronidazole 500 mg twice daily for seven days [3]. Although vaginal metronidazole has not been studied during breastfeeding, 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 [92].

Clindamycin – While oral clindamycin is a reasonable therapeutic choice, we prefer oral metronidazole because clindamycin has the potential to cause adverse effects on the breastfed infant's gastrointestinal flora. Infants of patients treated with oral clindamycin should be monitored for diarrhea, candidiasis (thrush, diaper rash) or, rarely, blood in the stool indicating possible antibiotic-associated colitis [92]. Infant side effects are less likely with vaginal clindamycin than oral use since only approximately 30 percent of a vaginal dose is absorbed.

Alternative drugs – For lactating individuals who are administered tinidazole or secnidazole, interruption of breastfeeding is recommended during treatment and for three days after the last dose based on animal data (tinidazole only) [3,44].

Safety – 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 [92]. Outcomes data of maternal metronidazole use did not show a significant increase in adverse events compared with 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.

INDIVIDUALS UNDERGOING GYNECOLOGIC PROCEDURES — For individuals with confirmed BV (with or without symptoms), we suggest antibiotic treatment prior to transvaginal procedures or surgery (eg, pregnancy termination, dilation and curettage, hysterectomy) to prevent postprocedure infection (cuff infection after hysterectomy, endometritis after termination) [93,94]. Reported reductions in postoperative infectious complications range from 10 to 75 percent [95-99]. There is insufficient evidence to make a conclusion regarding screening for BV prior to intrauterine device insertion [100]. The medication treatment options are the same as for symptomatic non-pregnant females (See 'Preferred treatments' above.)

TREATMENT OF SEXUAL PARTNERS — Although sexual activity is a risk factor for transmission, the data do not support treatment of asymptomatic sexual partners of individuals with confirmed BV. In a 2016 meta-analysis of seven trials assessing efficacy of BV treatment versus placebo in women and their male sexual partners, antibiotic treatment of the sexual partners did not increase the rate of clinical or symptomatic improvement for the index patients nor did it reduce the rate of recurrence during a four-week study period [101]. The men in the treatment group reported more adverse events compared with men in the placebo group. Individuals with documented BV infection should encourage sexual partners who have a vagina to be aware of the signs and symptoms of BV given the high risk of concordant infection (25 to 50 percent) [102]. While treatment of confirmed infection is indicated for relief of symptoms, the available data do not support treatment of asymptomatic sexual partners.

Individuals with a penis or phallus — There is no strong evidence that treatment of sex partners who have a penis or phallus impacts the treatment success or risk of recurrence for the individual with confirmed BV [3,103,104]. As examples:

In a trial of 214 individuals with recurrent BV, seven-day metronidazole treatment of male partners, compared with placebo treatment, did not reduce BV recurrence in intention-to-treat analysis [104]. Although not statistically significant, BV recurrence was less likely in individuals whose male partners were adherent to the study medication.

In a study of 22 heterosexual couples in which the female partner had symptomatic BV confirmed by testing, treatment of male partners with topical penile clindamycin 2% cream for seven days, in addition to oral metronidazole, was associated with immediate decrease in the prevalence of BV-associated bacteria in the penile skin [105]. The female partners were treated with oral metronidazole 400 mg twice daily for seven days.

Individuals with a vagina or neovagina — Individuals with a vagina or neovagina who are sexual partners of those with confirmed BV should be educated about the signs and symptoms of BV given the high risk of concordant infection (25 to 50 percent) [102,106,107]. In patients with confirmed BV infection, treatment is indicated for relief of symptoms. It has been hypothesized that behavioral interventions that reduce transfer of vaginal fluid between sex partners who have vaginas 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 [108]. Further study is needed. (See "Lesbian, gay, bisexual, transgender, and other sexual minority women: Medical and reproductive care", section on 'Sexually transmitted infection'.)

RELAPSE AND RECURRENT INFECTION

Recurrence versus reinfection – Approximately 30 percent of patients with initial responses to therapy have a recurrence of symptoms within three months [28], and more than 50 percent experience a recurrence within 12 months [109]. 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 [110]. This mechanism may explain the persistence of pathogenic bacteria, as documented by 16S rRNA sequencing and polymerase chain reaction (PCR) testing, in patients with documented infection who are treated with seven days of oral metronidazole therapy [111].

The only interventions proven to reduce development or recurrence of BV are chronic suppressive therapy and circumcision of male partners [112,113].

Treatment – Limited data are available regarding the optimal treatment strategy for women with recurrent BV [3]. We suggest symptomatic relapse be treated initially with a seven-day course of oral or vaginal metronidazole or clindamycin, especially if one class has not been previously prescribed. Alternatively, vaginal boric acid suppositories for 30 days can be used as an induction regimen simultaneously or to follow seven-day oral antibiotic treatment [3,114]. The treatment regimen may be the same or different from the initial or previous treatment regimen [3]. 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. Boric acid should not be used by individuals who are pregnant or attempting conception. Sexual partners of patients treated with vaginal boric acid have reported skin irritation after exposure [115]. The magnitude and duration of risk from the time of boric acid use is not known.

After initial induction therapy, most individuals 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 suppressive regimen consisting of maintenance metronidazole vaginal gel. Long-term clindamycin regimens, oral or topical, are not advised because of toxicity (oral) and lack of documented efficacy (topical) [116].

Metronidazole monotherapy – For patients with recurrent BV, we first prescribe metronidazole gel 0.75% or an oral nitroimidazole for 7 to 10 days followed by twice-weekly dosing of metronidazole gel for four to six months [3]. The choice of initial treatment (vaginal gel or oral pill) is based upon availability and patient preferences. In one multicenter prospective trial of this prophylactic metronidazole gel regimen, recurrent BV occurred in 25.5 percent of patients on suppressive therapy versus 59.1 percent of those receiving placebo [112]. However, cure of BV following cessation of the prophylactic regimen remains elusive. Secondary vaginal candidiasis was a common side effect.

Combination therapy followed by suppression therapy – As discussed above, results can be improved by adding vaginal boric acid to the initial oral nitroimidazole induction therapy; vaginal boric acid alone is ineffective [114]. Metronidazole or tinidazole is taken orally for seven days, and vaginal boric acid 600 mg once daily at bedtime is begun at the same time and continued for 21 days [3]. Patients are seen for follow-up a day or two after their last vaginal 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 once treatment has been completed.

Intravaginal L. crispatus – Intravaginal treatment with Lactobacillus crispatus is a promising therapy to follow the initial course of metronidazole. In a phase 2b trial comparing vaginal L. crispatus CTV-05 (LACTIN-V) with placebo in 228 women diagnosed with BV, patients receiving LACTIN-V had fewer BV recurrences at 12 and 24 weeks of follow-up (recurrence rate 12 weeks: 30 versus 45 percent; 24 weeks: 39 versus 54 percent) [49]. Treatment with LACTIN-V also resulted in higher rates of detectable vaginal L. crispatus compared with placebo (12 weeks: 79 versus 6 percent; 24 weeks: 48 versus 2 percent). All patients initially received seven days of vaginal metronidazole followed by 11 weeks of either therapy or placebo. Adverse event rates were similar between the two groups; no serious adverse events were attributable to either therapy. This approach is promising both for eliminating BV and for restoring Lactobacillus colonization. However, limitations include that 30 percent of patients experienced recurrence during active treatment and outcomes were not studied beyond three months. In addition, the product is not commercially available, and study results should not be extrapolated to other probiotic remedies.

Although supporting data are lacking, those with a metronidazole allergy can be treated with either topical clindamycin gel or undergo metronidazole desensitization. As noted above, topical clindamycin gel (2%) is less effective, which is why metronidazole gel is preferred. In our experience, clindamycin therapy is frequently associated with vaginal yeast coinfections compared with metronidazole gel. Clindamycin should not be used in patients with a history of C. difficile infection.

Metronidazole maintenance of remission – As discussed above, results can be improved by adding vaginal boric acid to the initial oral nitroimidazole induction therapy; vaginal boric acid alone is ineffective [114]. Metronidazole or tinidazole is taken orally for seven days, and vaginal boric acid 600 mg once daily at bedtime is begun at the same time and continued for 21 days [3]. Patients are seen for follow-up a day or two after their last vaginal 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 once treatment has been completed.

Less well-studied treatment options for recurrent infections include:

Use of condoms or abstinence – Several studies have reported reduced rates of recurrence when sexual partners used condoms routinely with coitus or the patient remained abstinent [31,109,116-119]. For this reason, some experts suggest these behavioral interventions for individuals with recurrent infection.

Combination therapy – In a trial of Kenyan HIV-seronegative sex workers treated with either combination metronidazole plus fluconazole or placebo, dosed monthly, women receiving combination treatment had fewer episodes of BV infection [120]. In a different trial of Kenyan HIV-seronegative women comparing combination treatment (metronidazole and miconazole) with placebo, treatment was associated with a reduced proportion of visits with BV over a 12-month period (21 percent in treatment group versus 32.5 percent in placebo group) [121]. In both trials, there was no impact on infection with vulvovaginal candidiasis or trichomoniasis. More trial data are needed before these therapies can be applied to a broad population.

For patients with recurrent BV, an observational study of a multidose vaginal regimen that combined high-dose metronidazole with miconazole reported short-term remission in 68 percent of patients [122]. This combination is not commercially available.

Treatment with lactobacillus – 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 [23,123]. These results should be reproduced in other trials before use of this therapy is considered.

Vaginal microbiome transplant – Vaginal microbiome transplant is under investigation in pilot studies without controls involving small numbers of women with recurrent BV as a potential treatment for patients with recurrent BV infection [124,125]. More data are needed before this approach becomes a standard therapy.

Ineffective therapies

Vaginal acidifying agents – 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.

Probiotics – In a randomized trial, probiotics were not more effective than placebo for prevention of relapse [116].

PREVENTION — Use of condoms and hormonal contraceptives may be protective factors [104,116].

Condom use — Some studies have reported reduced rates of recurrence when male sexual partners used condoms routinely during coitus [116-119]. In a trial studying female BV recurrence after male partner treatment with metronidazole or placebo, condom use at the last sexual encounter (as reported by both sexual partners) was associated with lower recurrence rates of BV in univariate analysis (47 versus 83 to 84 percent) [104]. The trend remained in multivariate analysis but was no longer statistically significant. Correct and consistent use of either external or internal condoms also reduces chance of pregnancy and risk of sexually transmitted infections (STIs) [104,126].

(See "External (formerly male) condoms", section on 'Protection from STIs'.)

(See "Female condoms", section on 'Sexually transmitted infections'.)

Hormonal contraception — Use of hormonal contraception has been associated with reductions in BV, although the majority of data are observational. As examples:

In a retrospective study of 682 women using a variety of contraceptives who underwent 16S rRNA gene analysis of their vaginal samples, those using combined estrogen-progestin oral contraceptives (COCs) were 70 percent less likely to have BV-associated bacterial colonization and were nearly twice as likely to have H2O2-producing lactobacillus species compared with those using condoms [127].

A meta-analysis of 55 studies (mainly observational) reported that hormonal contraceptive use was associated with reduced odds of prevalent BV (pooled effect size by random effects 0.68, 95% CI 0.63-0.73) [128]. Combined estrogen-progestin and progestin-only contraceptives were associated with both reduced BV prevalence and incidence.

Probiotics — The role of probiotics in BV prevention is not yet known. (See 'Role of probiotics' above.)

RECURRENT INFECTION

Recurrence frequency and mechanisms — Approximately 30 percent of patients with initial responses to therapy have a recurrence of symptoms within three months [28], and more than 50 percent experience a recurrence within 12 months [109]. Individuals with more than three documented BV episodes in one year are defined as having recurrent BV [11].

Individuals with isolated repeat confirmed BV infections are treated in the manner described above.

Individuals with documented recurrent BV, as defined by more than three confirmed infections in one year, receive induction therapy followed long-term suppressive therapy.

The explanation for this high rate of recurrence is unclear. Three hypothesized causes include [129]:

Treatment non-adherence.

Reinfection, through sexual transmission from both male and female partners. Although this has not been directly confirmed, there are strong epidemiologic data.

Relapse resulting from 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 [110]. This mechanism may explain the persistence of pathogenic bacteria, as documented by 16S rRNA sequencing and polymerase chain reaction (PCR) testing, in patients with documented infection who are treated with seven days of oral metronidazole therapy [111]. Biofilm lysis as a potential BV therapy is under investigation [130].

Treatment of recurrent BV — Given that limited data are available to guide the optimal treatment strategy for individuals with recurrent BV [3], we believe any patient with more than three documented episodes of BV in the previous 12 months should receive induction therapy, ideally with a different agent from what was initially used, followed by a long-term maintenance regimen consisting of maintenance metronidazole vaginal gel.

Induction therapy followed by suppressive treatment Clinicians have taken multiple approaches in attempting to eradicate recurrent confirmed BV infections [131]; in the absence of comparative data, all approaches are reasonable. Treatment selection is driven by patient preference, availability of agents, and cost.

Metronidazole regimen – For patients with recurrent BV, we suggest initial metronidazole gel 0.75% given as a 5-gram dose or an oral nitroimidazole for seven days followed by twice-weekly dosing of metronidazole 0.75% gel 5-gram dose for four to six months [3]. The choice of initial treatment (vaginal gel or oral pill) is based upon availability and patient preferences. In one multicenter prospective trial comparing this metronidazole gel regimen with placebo, recurrent BV occurred 26 versus 59 percent of patients, respectively [112]. Secondary vaginal candidiasis was a common side effect.

Vaginal boric acid regimenVaginal boric acid has been used for both induction and suppression therapy but not studied [131]:

-Induction Vaginal boric acid 300 or 600 mg daily for 7 to 14 days, followed by:

-SuppressionVaginal boric acid 300 or 600 mg inserted two to three times per week. For simplicity, the dose of vaginal boric acid used for suppression (300 or 600 mg) is the same as the one selected for induction treatment.

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. Boric acid should not be used by individuals who are pregnant or attempting conception. Sexual partners of patients treated with vaginal boric acid have reported skin irritation after exposure [115]. The magnitude and duration of risk for skin irritation from the time of boric acid use is not known.

Triple-phase regimen – For this approach an oral nitroimidazole is used concurrently with vaginal boric acid followed by prolonged treatment with vaginal metronidazole gel if the initial treatment achieves remission [114,132].

-Treatment protocols – An oral nitroimidazole (metronidazole or tinidazole) is taken orally for seven days with vaginal boric acid 600 mg once daily at bedtime [114,132]. The oral nitroimidazole is stopped after seven days, but the vaginal boric acid is continued for 21 to 30 days of total treatment. The oral nitroimidazole may be the same or different from the initial or previous treatment regimen [3]. Patients are seen for follow-up a day or two after their last vaginal boric acid dose. If they are in remission based on Amsel criteria or similar, they immediately begin metronidazole gel 0.75%, 5 gram vaginally twice weekly for four to six months as suppressive therapy [114,132]. Therapy is then discontinued once treatment has been completed.

-Supporting data – In an observational study of 93 patients with recurrent BV treated with a triple-phase regimen, 99 percent (92 out of 93) were asymptomatic with ≤2 Amsel criteria at the first follow-up visit (mean 32 days) [132]. By six months from treatment, 70 percent (48 out of 69) remained in remission while 30 percent (21 out of 69) had relapsed. During the maintenance phase, five patients declined to participate, and 18 were lost to follow-up. A retrospective chart review of 58 women treated with a triple-phase regimen for recurrent BV reported initial cure rates of 88 to 92 percent at 7 to 12 weeks of follow-up followed by cumulative cure rates of 87, 78, and 65 percent at 12, 16, and 28 weeks, respectively [114]. By 36 weeks of follow-up, the failure rate had risen to 50 percent.

Less well-studied treatment options for recurrent infections include:

Use of condoms or abstinence – Some studies have reported reduced rates of recurrence when sexual partners used condoms routinely with coitus or the patient remained abstinent [31,109,116-119]. For this reason, some experts suggest these behavioral interventions for those with recurrent infection. However, direct prospective trial data supporting these interventions are lacking.

Combination prophylactic therapy – In a trial of Kenyan HIV-seronegative sex workers treated with either combination metronidazole plus fluconazole or placebo, dosed monthly, women receiving combination treatment had fewer episodes of BV infection [120]. In a different trial of Kenyan HIV-seronegative women comparing combination treatment (metronidazole and miconazole) with placebo, treatment was associated with a reduced proportion of visits with BV over a 12-month period (21 percent in treatment group versus 32.5 percent in placebo group) [121]. In both trials, there was no impact on infection with vulvovaginal candidiasis or trichomoniasis. More trial data are needed before these therapies can be applied to a broad population.

For patients with recurrent BV, an observational study of a multidose vaginal regimen that combined high-dose metronidazole with miconazole reported short-term remission in 68 percent of patients [122]. This combination is not commercially available.

Treatment with lactobacillus – 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 [23,123]. These results should be reproduced in other trials before use of this therapy is considered.

Investigational

-Vaginal Lactobacillus crispatus – Intravaginal treatment with Lactobacillus crispatus is a promising therapy to follow the initial course of metronidazole [133]. In a phase 2b trial comparing vaginal L. crispatus CTV-05 (LACTIN-V) with placebo in 228 women diagnosed with BV, patients receiving LACTIN-V had fewer BV recurrences at 12 and 24 weeks of follow-up (recurrence rate 12 weeks: 30 versus 45 percent; 24 weeks: 39 versus 54 percent) [49]. Treatment with LACTIN-V also resulted in higher rates of detectable vaginal L. crispatus compared with placebo (12 weeks: 79 versus 6 percent; 24 weeks: 48 versus 2 percent). All patients initially received seven days of vaginal metronidazole followed by 11 weeks of either therapy or placebo. Adverse event rates were similar between the two groups; no serious adverse events were attributable to either therapy. This approach is promising both for eliminating BV and for restoring Lactobacillus colonization. However, limitations include that 30 percent of patients experienced recurrence during active treatment, and outcomes were not studied beyond three months. In addition, the product is not commercially available, and study results should not be extrapolated to other probiotic remedies.

-Vaginal microbiome transplant – Vaginal microbiome transplant is under investigation in pilot studies without controls involving small numbers of women with recurrent BV as a potential treatment for patients with recurrent BV infection [124,125]. More data are needed before this approach becomes a standard therapy.

Ineffective therapies

Clindamycin for long-term suppression – While initial symptomatic relapse can be treated with a seven-day course of oral or vaginal clindamycin, long-term clindamycin regimens, oral or topical, are not advised because of toxicity (oral) and lack of documented efficacy (topical) [116]. In our experience, clindamycin therapy is frequently associated with vaginal yeast coinfections compared with metronidazole gel. Clindamycin should not be used in women with a history of C. difficile infection.

Vaginal acidifying agents – 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.

Probiotics – In a randomized trial, probiotics were not more effective than placebo for prevention of relapse. (See 'Probiotics' above.)

Antimicrobial resistance — While drug-resistant species and genes would explain recurrent infection, antimicrobial resistance has not been well studied or documented, although available evidence is sparse and limited to in vitro studies [35]. In addition, use of PCR and molecular techniques have identified BV pathogens that have not been successfully grown in culture and thus the drug susceptibility and sensitivities of these organisms are not yet known [134]. More information is needed in this area.

Interventions to reduce recurrence risk — The only interventions proven to reduce development or recurrence of BV are chronic suppressive therapy and circumcision of male partners [112,113]. A trial that compared treatment of male partners with metronidazole (seven days) or placebo reported trends toward reduced BV recurrence for individuals whose male partners were adherent to the study medication or who used condoms, but the findings did not reach statistical significance [104]. Consistent and correct condom use may be helpful, but routine treatment of sexual partners is not advised at this time.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bacterial vaginosis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

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.)

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Beyond the Basics topics

SUMMARY AND RECOMMENDATIONS

Non-pregnant females or individuals with a vagina

Symptomatic – For non-pregnant females with symptomatic BV, we suggest multiday treatment with metronidazole or clindamycin rather than other antibiotics (Grade 2C). Treatment of symptomatic females with confirmed bacterial vaginosis (BV) is indicated to reduce symptoms (typically vaginal discharge and odor), reduce postoperative infections following common gynecologic procedures, and reduce the risk of acquisition of sexually transmitted infections (STIs). As efficacy is similar for oral or vaginal regimens of both metronidazole or clindamycin, choice of treatment route is driven by patient preference around treatment route, drug availability, and cost. (See 'Preferred treatments' above.)

Oral tinidazole and secnidazole have demonstrated efficacy similar to that of oral metronidazole and convenient dosing. However, as they also tend to be of higher cost and lesser availability, they are considered alternatives to the treatments above. (See 'Alternative drugs' above.)

Preferred treatment regimens include:

-Metronidazole 500 mg twice daily orally for seven days.

or

-Metronidazole gel 0.75% (5 grams containing 37.5 mg metronidazole) once daily vaginally for five days.

or

-Clindamycin 2% vaginal cream once daily at bedtime for seven days. During therapy with clindamycin cream, latex condoms should not be used. (See 'Metronidazole' above and 'Clindamycin' above.)

Asymptomatic – For non-pregnant females with asymptomatic BV, we suggest observation rather than antibiotic treatment (Grade 2C). Treatment 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. (See 'Nonpregnant asymptomatic females' above.)

Pregnant individuals – Pregnant persons with BV are at increased risk of preterm birth, but the role of screening and treating asymptomatic pregnant individuals is debated because the available data conflict.

Pregnant with symptoms – For symptomatic pregnant individuals with confirmed BV, we recommend treatment with antibiotics rather than observation (Grade 1B). Oral treatment is effective at eradicating BV and its symptoms. Antibiotic treatment has not been associated with adverse fetal or obstetric effects. We prescribe metronidazole 500 mg orally twice daily for seven days or clindamycin 300 mg orally twice daily for seven days. (See 'Symptomatic' above.)

Pregnant without symptoms – For asymptomatic pregnant individuals, we suggest not screening or treating for BV (Grade 2C). There is no consistent evidence that screening and treatment of asymptomatic infection reduces the risk of preterm birth. (See 'Asymptomatic infection and screening' above.)

Gynecologic surgery – For individuals with confirmed BV who are planning gynecologic surgery that involves the vagina, we suggest treatment rather than observation, even in the absence of symptoms (Grade 2C). Preoperative treatment decreases the frequency of postoperative infectious complications. (See 'Individuals undergoing gynecologic procedures' above.)

Sexual partners – For sexual partners of individuals with confirmed BV, we recommend not treating with antibiotics (Grade 1B). Antibiotic treatment has not been associated with increased rates of clinical or symptomatic improvement nor reduction of recurrence rates; antibiotic therapy has been associated with side effects. (See 'Treatment of Sexual partners' above.)

Recurrent BV – 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 recurrence using a different antibiotic than that used for the initial episode. Individuals with more than three documented BV episodes in one year are defined as having recurrent BV. (See 'Relapse and recurrent infection' above.)

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  77. US Preventive Services Task Force, Owens DK, Davidson KW, et al. Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: US Preventive Services Task Force Recommendation Statement. JAMA 2020; 323:1286.
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  81. 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.
  82. 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.
  83. 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.
  84. 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.
  85. Eschenbach DA. Bacterial vaginosis: emphasis on upper genital tract complications. Obstet Gynecol Clin North Am 1989; 16:593.
  86. 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.
  87. 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.
  88. Thinkhamrop J, Hofmeyr GJ, Adetoro O, et al. Antibiotic prophylaxis during the second and third trimester to reduce adverse pregnancy outcomes and morbidity. Cochrane Database Syst Rev 2015; :CD002250.
  89. Odendaal HJ, Popov I, Schoeman J, et al. Preterm labour--is bacterial vaginosis involved? S Afr Med J 2002; 92:231.
  90. 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.
  91. 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.
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  94. ACOG Practice Bulletin No. 195: Prevention of Infection After Gynecologic Procedures. Obstet Gynecol 2018; 131:e172.
  95. 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.
  96. 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.
  97. Miller L, Thomas K, Hughes JP, et al. Randomised treatment trial of bacterial vaginosis to prevent post-abortion complication. BJOG 2004; 111:982.
  98. 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.
  99. 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.
  100. Caddy S, Yudin MH, Hakim J, et al. Best practices to minimize risk of infection with intrauterine device insertion. J Obstet Gynaecol Can 2014; 36:266.
  101. Amaya-Guio J, Viveros-Carreño DA, Sierra-Barrios EM, et al. Antibiotic treatment for the sexual partners of women with bacterial vaginosis. Cochrane Database Syst Rev 2016; 10:CD011701.
  102. 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.
  103. Potter J. Should sexual partners of women with bacterial vaginosis receive treatment? Br J Gen Pract 1999; 49:913.
  104. Schwebke JR, Lensing SY, Lee J, et al. Treatment of Male Sexual Partners of Women With Bacterial Vaginosis: A Randomized, Double-Blind, Placebo-Controlled Trial. Clin Infect Dis 2021; 73:e672.
  105. Plummer EL, Vodstrcil LA, Danielewski JA, et al. Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: Acceptability, tolerability and impact on the genital microbiota of couples - A pilot study. PLoS One 2018; 13:e0190199.
  106. Jain A, Bradbeer C. A case of successful management of recurrent bacterial vaginosis of neovagina after male to female gender reassignment surgery. Int J STD AIDS 2007; 18:140.
  107. Birse KD, Kratzer K, Zuend CF, et al. The neovaginal microbiome of transgender women post-gender reassignment surgery. Microbiome 2020; 8:61.
  108. 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.
  109. 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.
  110. 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.
  111. Verwijs MC, Agaba SK, Darby AC, van de Wijgert JHHM. Impact of oral metronidazole treatment on the vaginal microbiota and correlates of treatment failure. Am J Obstet Gynecol 2020; 222:157.e1.
  112. 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.
  113. 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.
  114. Reichman O, Akins R, Sobel JD. Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis. Sex Transm Dis 2009; 36:732.
  115. Barbieri R, Harvard Medical School, Harvard University, 2021, personal communication.
  116. 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.
  117. 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.
  118. Schwebke JR, Desmond R. Risk factors for bacterial vaginosis in women at high risk for sexually transmitted diseases. Sex Transm Dis 2005; 32:654.
  119. Smart S, Singal A, Mindel A. Social and sexual risk factors for bacterial vaginosis. Sex Transm Infect 2004; 80:58.
  120. McClelland RS, Richardson BA, Hassan WM, et al. Improvement of vaginal health for Kenyan women at risk for acquisition of human immunodeficiency virus type 1: results of a randomized trial. J Infect Dis 2008; 197:1361.
  121. McClelland RS, Balkus JE, Lee J, et al. Randomized Trial of Periodic Presumptive Treatment With High-Dose Intravaginal Metronidazole and Miconazole to Prevent Vaginal Infections in HIV-negative Women. J Infect Dis 2015; 211:1875.
  122. Sobel JD, Kaur N, Woznicki NA, et al. Conventional oral and secondary high dose vaginal metronidazole therapy for recurrent bacterial vaginosis: clinical outcomes, impacts of sex and menses. Infect Drug Resist 2019; 12:2297.
  123. 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.
  124. Ma D, Chen Y, Chen T. Vaginal microbiota transplantation for the treatment of bacterial vaginosis: a conceptual analysis. FEMS Microbiol Lett 2019; 366.
  125. Lev-Sagie A, Goldman-Wohl D, Cohen Y, et al. Vaginal microbiome transplantation in women with intractable bacterial vaginosis. Nat Med 2019; 25:1500.
  126. Beksinska M, Wong R, Smit J. Male and female condoms: Their key role in pregnancy and STI/HIV prevention. Best Pract Res Clin Obstet Gynaecol 2020; 66:55.
  127. Brooks JP, Edwards DJ, Blithe DL, et al. Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome. Contraception 2017; 95:405.
  128. Vodstrcil LA, Hocking JS, Law M, et al. Hormonal contraception is associated with a reduced risk of bacterial vaginosis: a systematic review and meta-analysis. PLoS One 2013; 8:e73055.
  129. Sobel JD, Sobel R. Current and emerging pharmacotherapy for recurrent bacterial vaginosis. Expert Opin Pharmacother 2021; 22:1593.
  130. Landlinger C, Tisakova L, Oberbauer V, et al. Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo. Pathogens 2021; 10.
  131. Powell A, Ghanem KG, Rogers L, et al. Clinicians' Use of Intravaginal Boric Acid Maintenance Therapy for Recurrent Vulvovaginal Candidiasis and Bacterial Vaginosis. Sex Transm Dis 2019; 46:810.
  132. Surapaneni S, Akins R, Sobel JD. Recurrent Bacterial Vaginosis: An Unmet Therapeutic Challenge. Experience With a Combination Pharmacotherapy Long-Term Suppressive Regimen. Sex Transm Dis 2021; 48:761.
  133. Lagenaur LA, Hemmerling A, Chiu C, et al. Connecting the Dots: Translating the Vaginal Microbiome Into a Drug. J Infect Dis 2021; 223:S296.
  134. Javed A, Parvaiz F, Manzoor S. Bacterial vaginosis: An insight into the prevalence, alternative treatments regimen and it's associated resistance patterns. Microb Pathog 2019; 127:21.
Topic 113103 Version 24.0

References

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36 : Tinidazole (Tindamax)--a new option for treatment of bacterial vaginosis.

37 : Comparison of tinidazole given as a single dose and on 2 consecutive days for the treatment of nonspecific bacterial vaginosis.

38 : Comparison of tinidazole given as a single dose and on 2 consecutive days for the treatment of nonspecific bacterial vaginosis.

39 : Effectiveness of two tinidazole regimens in treatment of bacterial vaginosis: a randomized controlled trial.

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41 : Tinidazole vs metronidazole for the treatment of bacterial vaginosis.

42 : 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.

43 : A phase-3, double-blind, placebo-controlled study of the effectiveness and safety of single oral doses of secnidazole 2 g for the treatment of women with bacterial vaginosis.

44 : A phase-3, double-blind, placebo-controlled study of the effectiveness and safety of single oral doses of secnidazole 2 g for the treatment of women with bacterial vaginosis.

45 : Low-dose secnidazole in the treatment of bacterial vaginosis.

46 : Secnidazole Treatment of Bacterial Vaginosis: A Randomized Controlled Trial.

47 : Probiotics for the treatment of bacterial vaginosis.

48 : Probiotics for the treatment of women with bacterial vaginosis.

49 : Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis.

50 : Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis.

51 : Comparison of clindamycin phosphate vaginal cream with triple sulfonamide vaginal cream in the treatment of bacterial vaginosis.

52 : Erythromycin versus metronidazole in the treatment of bacterial vaginosis.

53 : Bacterial vaginosis. An evaluation of treatment.

54 : Efficacy of povidone-iodine vaginal suppositories in the treatment of bacterial vaginosis.

55 : Amoxicillin treatment of bacterial vaginosis during pregnancy.

56 : Bacterial vaginosis diagnosed at the first antenatal visit better predicts preterm labour than diagnosis later in pregnancy.

57 : Antiseptics and disinfectants for the treatment of bacterial vaginosis: a systematic review.

58 : Safety and Efficacy of a Novel Vaginal Anti-infective, TOL-463, in the Treatment of Bacterial Vaginosis and Vulvovaginal Candidiasis: A Randomized, Single-blind, Phase 2, Controlled Trial.

59 : A randomized trial of metronidazole in asymptomatic bacterial vaginosis to prevent the acquisition of sexually transmitted diseases.

60 : Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group.

61 : Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial.

62 : Effect of treatment of asymptomatic bacterial vaginosis on HIV-1 shedding in the genital tract among women on antiretroviral therapy: a pilot study.

63 : Asymptomatic Bacterial Vaginosis: To Treat or Not to Treat?

64 : Antibiotics for treating bacterial vaginosis in pregnancy.

65 : Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised, placebo controlled trial.

66 : Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study.

67 : Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis.

68 : Antibiotic treatment of bacterial vaginosis in pregnancy: a meta-analysis.

69 : Antibiotics for bacterial vaginosis or Trichomonas vaginalis in pregnancy: A systematic review.

70 : Screening for bacterial vaginosis in pregnancy.

71 : Treatment of vaginal infections to prevent preterm birth: a meta-analysis.

72 : Intravaginal clindamycin treatment for bacterial vaginosis: effects on preterm delivery and low birth weight.

73 : Is metronidazole teratogenic? A meta-analysis.

74 : 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.

75 : Practice bulletin no. 130: prediction and prevention of preterm birth.

76 : Screening and management of bacterial vaginosis in pregnancy.

77 : Screening for Bacterial Vaginosis in Pregnant Persons to Prevent Preterm Delivery: US Preventive Services Task Force Recommendation Statement.

78 : Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis.

79 : Screening for bacterial vaginosis in pregnancy to prevent preterm delivery: U.S. Preventive Services Task Force recommendation statement.

80 : 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.

81 : Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora.

82 : A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth.

83 : Is bacterial vaginosis a stronger risk factor for preterm birth when it is diagnosed earlier in gestation?

84 : Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome.

85 : Bacterial vaginosis: emphasis on upper genital tract complications.

86 : A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity.

87 : Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis.

88 : Antibiotic prophylaxis during the second and third trimester to reduce adverse pregnancy outcomes and morbidity.

89 : Preterm labour--is bacterial vaginosis involved?

90 : Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection.

91 : 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.

92 : 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.

93 : Bacterial vaginosis and surgical site infections.

94 : ACOG Practice Bulletin No. 195: Prevention of Infection After Gynecologic Procedures.

95 : A randomised comparison of strategies for reducing infective complications of induced abortion.

96 : 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.

97 : Randomised treatment trial of bacterial vaginosis to prevent post-abortion complication.

98 : Antibiotic prophylaxis to prevent post-abortal upper genital tract infection in women with bacterial vaginosis: randomised controlled trial.

99 : Incidence of pelvic inflammatory disease after first-trimester legal abortion in women with bacterial vaginosis after treatment with metronidazole: a double-blind, randomized study.

100 : Best practices to minimize risk of infection with intrauterine device insertion.

101 : Antibiotic treatment for the sexual partners of women with bacterial vaginosis.

102 : The influence of behaviors and relationships on the vaginal microbiota of women and their female partners: the WOW Health Study.

103 : Should sexual partners of women with bacterial vaginosis receive treatment?

104 : Treatment of Male Sexual Partners of Women With Bacterial Vaginosis: A Randomized, Double-Blind, Placebo-Controlled Trial.

105 : Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: Acceptability, tolerability and impact on the genital microbiota of couples - A pilot study.

106 : A case of successful management of recurrent bacterial vaginosis of neovagina after male to female gender reassignment surgery.

107 : The neovaginal microbiome of transgender women post-gender reassignment surgery.

108 : A behavioural intervention to reduce persistence of bacterial vaginosis among women who report sex with women: results of a randomised trial.

109 : High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence.

110 : An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole.

111 : Impact of oral metronidazole treatment on the vaginal microbiota and correlates of treatment failure.

112 : Suppressive antibacterial therapy with 0.75% metronidazole vaginal gel to prevent recurrent bacterial vaginosis.

113 : The effects of male circumcision on female partners' genital tract symptoms and vaginal infections in a randomized trial in Rakai, Uganda.

114 : Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis.

115 : Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis.

116 : Recurrence of bacterial vaginosis is significantly associated with posttreatment sexual activities and hormonal contraceptive use.

117 : Intravaginal metronidazole gel versus metronidazole plus nystatin ovules for bacterial vaginosis: a randomized controlled trial.

118 : Risk factors for bacterial vaginosis in women at high risk for sexually transmitted diseases.

119 : Social and sexual risk factors for bacterial vaginosis.

120 : Improvement of vaginal health for Kenyan women at risk for acquisition of human immunodeficiency virus type 1: results of a randomized trial.

121 : Randomized Trial of Periodic Presumptive Treatment With High-Dose Intravaginal Metronidazole and Miconazole to Prevent Vaginal Infections in HIV-negative Women.

122 : Conventional oral and secondary high dose vaginal metronidazole therapy for recurrent bacterial vaginosis: clinical outcomes, impacts of sex and menses.

123 : 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.

124 : Vaginal microbiota transplantation for the treatment of bacterial vaginosis: a conceptual analysis.

125 : Vaginal microbiome transplantation in women with intractable bacterial vaginosis.

126 : Male and female condoms: Their key role in pregnancy and STI/HIV prevention.

127 : Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome.

128 : Hormonal contraception is associated with a reduced risk of bacterial vaginosis: a systematic review and meta-analysis.

129 : Current and emerging pharmacotherapy for recurrent bacterial vaginosis.

130 : Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo.

131 : Clinicians' Use of Intravaginal Boric Acid Maintenance Therapy for Recurrent Vulvovaginal Candidiasis and Bacterial Vaginosis.

132 : Recurrent Bacterial Vaginosis: An Unmet Therapeutic Challenge. Experience With a Combination Pharmacotherapy Long-Term Suppressive Regimen.

133 : Connecting the Dots: Translating the Vaginal Microbiome Into a Drug.

134 : Bacterial vaginosis: An insight into the prevalence, alternative treatments regimen and it's associated resistance patterns.