INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Gardnerella vaginalis is a facultatively anaerobic gram-variable rod. It has been demonstrated to cause a wide variety of infections; however, it is most commonly recognized for its role as one of the organisms responsible for bacterial vaginosis (BV).

For related information, see Medscape's Women's Sexual Health Resource Center.

Pathophysiology

Bacterial vaginosis (BV), formerly known as nonspecific vaginitis, was named because bacteria are the etiologic agent in this infection and an associated inflammatory response is lacking.

BV is the most common cause of vaginitis and the most common infection encountered in the outpatient gynecologic setting.

An increase in vaginal discharge and vaginal malodor caused by a change in the vaginal flora characterizes BV.

The vaginal discharge of BV is characteristically described as a thin, gray, homogeneous fluid that is adherent to the vaginal mucosa.

Many studies have demonstrated the relationship of Gardnerella vaginalis with other bacteria in causing BV. BV is known to be a synergistic polymicrobic infection. Some of the associated bacteria include Lactobacillus species and anaerobes, including Mobiluncus, Bacteroides, Peptostreptococcus, Fusobacterium, Veillonella, and Eubacterium species. Mycoplasma hominis, Ureaplasma urealyticum, and Streptococcus viridans may also play a role in BV. Atopobium vaginae is now recognized as a pathogen associated with BV.¹

Evidence in support of a synergistic relationship includes the following: (1) Gardner and Dukes inoculated pure cultures of G vaginalis into the vaginas of healthy women and failed to produce BV symptoms; (2) inoculation of vaginal discharge fluid from BV patients into the vaginas of healthy women produced symptoms of BV; (3) treatment for BV, an antianaerobic antibiotic (metronidazole), is ineffective against G vaginalis; and (4) the volatile products elaborated from the whiff test are products of anaerobes and not of G vaginalis.

In BV, the vaginal flora becomes altered through known and unknown mechanisms, causing an increase in the local pH. This may result from a reduction in the hydrogen peroxide–producing lactobacilli. Lactobacilli are large rod-shaped organisms that help maintain the acidic pH of healthy vaginas and inhibit other anaerobic microorganisms through elaboration of hydrogen peroxide. Normally, lactobacilli are found in high concentrations in the healthy vagina. In BV, the lactobacilli population is reduced greatly, while populations of various anaerobes and G vaginalis are increased.

G vaginalis forms a biofilm in the vagina.² Some studies show that this biofilm may be resistant to some forms of medical treatment. This predominant G vaginalis biofilm has been shown to survive in hydrogen peroxide (H₂O₂), lactic acid, and high levels of antibiotics. When the biofilm was subjected in the laboratory to enzymatic dissolution, susceptibility to H₂O₂ and lactic acid were restored.² These findings may lead to future development of novel therapies involving enzymatic degradation of biofilms. No such products are currently on the market.

In a study published by Fredricks et al, G vaginalis was detected by PCR in 96% of subjects with BV and 70% of those without BV. Multiple other bacterial species were found by PCR in this study. Fredricks' study confirms the polymicrobial nature of BV and the presence of G vaginalis as one of the causative agents.³

Although BV is not considered a sexually transmitted disease, sexual activity has been linked to development of this infection. Observations in support of this include the following: (1) incidence of BV increases with an increase in the number of recent and lifetime sexual partners, (2) a new sexual partner can be related to BV, and (3) male partners of women with BV may have urethral colonization by the same organism, but the male is asymptomatic. Evidence that does not support an exclusive sexually transmitted role of BV is its occurrence in virginal females and its colonization of the rectum in virginal boys and girls.

Frequency

United States

Gardnerella vaginalis has been reported to occur in up to 100% of women with signs and symptoms of bacterial vaginosis (BV) and in up to 70% of women with no signs or symptoms of BV.

G vaginalis has been isolated in up to 80% of the urethras of male sexual partners of women with BV.

The incidence of BV in patients attending obstetric clinics is 10-25% and may be as high as 30-65% in patients attending sexually transmitted disease clinics.

Mortality/Morbidity

Uncomplicated bacterial vaginosis (BV) that is assessed promptly typically resolves with standard antibiotic treatment.

• Long-standing or untreated BV may lead to more serious sequelae, such as endometritis, salpingitis, pelvic inflammatory disease, or complications of pregnancy, including premature rupture of membranes, premature labor, chorioamnionitis, and postpartum endometritis.
• BV leads to an increased risk for acquiring HIV.³
• Postgynecologic procedure infections, such as vaginal cuff cellulitis (status posthysterectomy) and postabortion infection may also occur.
• Suspect concomitant infections (such as candida vaginitis) or newer, resistant organisms (Atopobium vaginae) in patients whose symptoms do not resolve after treatment of BV. See Treatment.

Race

Bacterial vaginosis appears to occur equally among people of all racial groups.

Sex

Gardnerella vaginalis colonization and/or infection predominantly occurs in women. Men rarely develop infections with G vaginalis; however, the urethras of men whose sexual partners have symptoms of BV are frequently colonized with the same strain of G vaginalis. A recent study by Bradshaw et al found that G vaginalis is not associated with nongonococcal urethritis.

Age

G vaginalis infections typically occur in women of reproductive age. Studies have documented G vaginalis colonization in prepubertal and/or virginal girls and boys and cases of BV occurring in prepubertal and/or virginal girls.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Vaginal odor is the most common, and often initial, symptom of bacterial vaginosis (BV). Odor may be recognized only after sexual intercourse. The alkalinity of semen may cause a release of volatile amines from the vaginal discharge and cause a fishy odor.
• Increased vaginal discharge is typically mild to moderate.
• Vulvar irritation is less common.
• Dysuria or dyspareunia occur rarely.
• Inquire about risk factors that may predispose patients to developing BV. Predisposing factors can include the following:
• • Recent antibiotic use
  • Decreased estrogen production of the host
  • Wearing an intrauterine device (IUD)
  • Douching
  • Sexual activity that could lead to transmission, as evidenced by the patient having a new sexual partner, an increased number of sexual partners in the month preceding the onset of BV symptoms, or having an increased number of lifetime sexual partners

Physical

• Vaginal discharge
• • Most often gray, thin, and homogeneous
  • Adherent to the vaginal mucosa
  • May not visualize pooling of discharge in the posterior fornix because of adherence to the vaginal mucosa
  • May observe small bubbles in the discharge fluid
• An increased light reflex of the vaginal walls may be observed, indicating a very wet appearance; however, typically, no or little evidence of inflammation is apparent.
• The labia, introitus, cervix, and cervical discharge appear normal.
• Evidence of cervicitis should prompt a workup for concomitant infection with Neisseria gonorrhoeae, Chlamydia trachomatis, or herpes simplex virus (HSV).

Causes

Bacterial vaginosis is a polymicrobic synergistic infection. As described in Pathophysiology, the normally predominant lactobacilli population is reduced in the vagina, while populations of Gardnerella vaginalis and other anaerobes are increased.

• G vaginalis is the only member of its genus.
• • Originally, it was known as Haemophilus vaginalis and then as Corynebacterium vaginale.
  • It is a nonmotile, nonflagellated, nonsporeforming, facultative anaerobic, and nonencapsulated bacteria.
  • Although G vaginalis appears microscopically as a gram-variable rod, it is officially categorized as a gram-negative rod.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Vaginal candidiasis

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Clinical diagnosis of bacterial vaginosis (BV) relies on history, vaginal examination, and microscopic examination (see the Table for a summary of the differential diagnoses). Emerging data support sending vaginal cultures in recalcitrant cases.⁴
• Historical information regarding the patient's symptoms and nature of the discharge
• • Most patients experience a vaginal malodor and/or an increase in vaginal discharge.
  • Vulvar irritation may be present or absent.
  • Dysuria, dyspareunia, and abdominal pain are lacking.
• Vaginal examination
• • Typical BV discharge characteristics
  • Lack of significant vulvovaginal inflammation
• Microscopic examination of the discharge: Demonstrating 3 of the following 4 Amsel's criteria is considered necessary to diagnose BV most accurately.⁵
• • Demonstration of clue cells on a saline smear is the most specific criterion for diagnosing BV. Clue cells are vaginal epithelial cells that have bacteria adherent to their surfaces. The edges of the squamous epithelial cells, which normally have a sharply defined cell border, become studded with bacteria. The epithelial cells appear to be peppered with coccobacilli.
  • A pH greater than 4.5 indicates infection, and pH may be elevated in up to 90% of patients with BV.
  • Characteristic discharge appearance is thin, gray, and homogeneous.
  • The whiff test may be positive in up to 70% of BV patients. This test is performed by placing a drop of 10% KOH on the speculum after the vaginal examination or mixing vaginal fluid with a drop of KOH on a microscope slide. The KOH, by virtue of its alkaline properties, causes the release of volatile amines from the vaginal fluid. The amines are products of anaerobic bacterial metabolism.
• The bacterial flora may be examined microscopically for evidence of changes in the overall bacterial predominance. The healthy vagina has a predominance of lactobacilli (large gram-positive rods). The flora of a patient with BV changes to become dominated by coccobacilli, reflecting an increase in the growth of Gardnerella vaginalis and other anaerobes.
• The vaginal discharge of patients with BV is notable for its lack of polymorphonuclear leukocytes (PMNs), typically 1 or less than 1 PMN per vaginal epithelial cell.
• Diagnosing BV accurately is more difficult when a coinfection is present. However, finding an increase in the number of PMNs per epithelial cell may lead the clinician to consider BV as a possibility.
• Obtaining routine vaginal cultures in patients with BV has no utility because this is a polymicrobial infection and some women may have asymptomatic carriage of G vaginalis organisms. Although G vaginalis has been demonstrated to grow in up to 100% of vaginal cultures of women with BV, it has also been cultured in up to 70% of asymptomatic women. However, obtaining cultures to exclude other infectious etiologies (eg, Trichomonas species, C trachomatis, N gonorrhoeae) is appropriate. In recurrent cases that have not resolved with standard regimens, cultures may be appropriate.

  Differential Diagnosis of the Vaginitides

  Clinical Elements		Bacterial Vaginosis	Trichomoniasis	Vaginal Candidiasis
  Symptoms	Vaginal odor	+	+/-	-
  	Vaginal discharge	Thin, gray, homogenous	Green-yellow	White, curdlike
  	Vulvar irritation	+/-	+	+
  	Dyspareunia	-	+	-
  Signs	Vulvar erythema	-	+/-	+/-
  	Bubbles in vaginal fluid	+	+/-	-
  	Strawberry cervix	-	+/-	-
  Microscopy	Saline wet mount
  	Clue cells	+	-	-
  	Motile protozoa	-	+	-
  	KOH test
  	Pseudohyphae	-	-	+
  	Whiff test	+	+/-	-
  	pH	>4.5	>4.5	<4.5

Procedures

No other procedures are necessary in the evaluation of patients with BV other than those listed in Lab Studies.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

• Antibiotics are the mainstay of therapy for bacterial vaginosis (BV).
• Asymptomatic women with Gardnerella vaginalis colonization do not need treatment.
• Studies of topically applied and orally administered yogurt/lactobacilli preparations, which are used to help reestablish the lactobacilli population in the vagina, have demonstrated inconsistent results.
• Some women with recurrent cases of BV may benefit from evaluation and/or treatment of G vaginalis colonization in their sexual partner. This approach is controversial.
• Treat BV occurring in pregnant women to reduce the risk of pregnancy-associated complications related to infection.
• Although not tested by clinical trials, treatment prior to cesarean delivery, total abdominal hysterectomy, and insertion of an IUD is also recommended.

Surgical Care

Surgery is not indicated for bacterial vaginosis.

Consultations

Consultation with an infectious disease specialist or obstetrician/gynecologist may be warranted for patients with nonresolving and/or recurring BV or more serious infections, such as endometritis, pelvic inflammatory disease, and chorioamnionitis.

Diet

Studies are conflicting regarding the efficacy of a diet supplemented with Lactobacillus (acidophilus).

Activity

Restriction of activities is not necessary for patients with bacterial vaginosis. Other, more serious Gardnerella infections may require restriction of activity based on the severity and nature of the illness.

MEDICATION

Section 7 of 10  

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• Follow-up
• Miscellaneous
• References

Antibiotics are the mainstay of therapy for bacterial vaginosis. Medications include metronidazole (Flagyl), clindamycin (Cleocin) oral or vaginal suppositories, and metronidazole vaginal gel (MetroGel-Vaginal).

Drug Category: Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Inpatient care is not necessary for patients with bacterial vaginosis.
• Obtain cultures of blood and infected tissue (if feasible) from inpatients who develop obstetric/gynecologic postoperative fever or signs of infection to try to elucidate the infectious etiologic organism. Blood cultures may not demonstrate growth of Gardnerella vaginalis unless gelatin is added to the media to prevent inhibition from the anticoagulant, sodium polyethanol sulfonate (SPS).

Further Outpatient Care

• Uncomplicated cases of bacterial vaginosis (BV) typically resolve after the standard antibiotic treatment.
• BV that does not resolve after one course of treatment may be cured by a second course with the same agent. Another option is to switch to another agent (ie, metronidazole to clindamycin, or clindamycin to metronidazole) as other concomitant organisms may respond better to an alternate medication. Metronidazole is favored because it allows faster return of colonization of H₂O₂-producing lactobacilli.⁶
• Some women with recurrent episodes of BV may benefit from treatment of Gardnerella vaginalis in their sexual partner if colonization is demonstrated. Repeating wet preps is useful because patients can develop new, non-BV infections such as Candida.
• Testing for other infections, such as N gonorrhoeae, C trachomatis, and herpes simplex virus type 1 (HSV-1) may be appropriate in individuals with BV because the incidence of sexually transmitted diseases (STDs) may be increased in this population depending upon the risk factors and demographics.
• Therapy with metronidazole or clindamycin may alter the vaginal flora and predispose the patient to development of vaginal candidiasis.

In/Out Patient Meds

Metronidazole and clindamycin are the preferred medications used to treat Gardnerella infections. See Medication for specific information on these medications.

Deterrence/Prevention

Predisposing factors that may contribute to development of bacterial vaginosis (BV) are listed below. Correction or modification of these factors may help reduce the incidence or recurrence of BV.

• Recent antibiotic use
• Decreased estrogen production of the host
• Wearing an IUD
• Douching
• Sexual activity leading to transmission, as evidenced by the patient having a new sexual partner, an increased number of sexual partners in the month preceding the onset of BV symptoms, and an increased number of lifetime sexual partners

Complications

• Bacterial vaginosis (BV) may lead to an increased risk of salpingitis and/or endometritis, postsurgical infections (eg, postcesarean endometritis, posthysterectomy vaginal cuff cellulitis), and adverse outcomes in pregnancy, including premature rupture of membranes, premature labor, chorioamnionitis, and postpartum endometritis.
• Mixed infections with Trichomonas and yeast can occur among patients with BV.
• Bacteremia
• • Gardnerella vaginalis bacteremia occurs much more commonly in women than in men and occurs most commonly in postpartum and postgynecologic procedure infections (eg, postpartum endometritis, chorioamnionitis, septic abortion) but is rare.
  • SPS, the anticoagulant used in blood culture media, is toxic to G vaginalis and inhibits its growth unless a neutralizing gelatin is added to counteract this effect. Routine blood cultures, therefore, may not grow G vaginalis, leading to underdiagnosis and underrecognition of this organism as the etiologic agent in these types of infections.
• Genitourinary infections
• • Although G vaginalis urinary tract infections (UTI) occur much more frequently in women than in men, the overall occurrence of G vaginalis as a causative etiology in this infection is low (<0.6%). However, the overall frequency may be underestimated because of a lack of optimal laboratory growth conditions (eg, aerobic incubation, short anaerobic growth period, urine not properly refrigerated prior to being cultured) and absence of associated pyuria occurring in women with concomitantly positive urine cultures.
  • In men, infections caused by G vaginalis are uncommon. Infection of the prostate and urinary bladder have been documented, although this occurs rarely and probably arises as a result of ascending spread of the organism from the colonized urethra. Balanoposthitis from G vaginalis has also been described.
• Other infections caused by G vaginalis include chorioamnionitis, endometritis, cervicitis, pelvic inflammatory disease, vaginal cuff cellulitis following hysterectomy, and bacteremia.
• Case reports include disc space infection (lumbar spine), vaginitis emphysematosa, liver abscess (postcesarean), neonatal meningitis, and neonatal cellulitis/skin abscess.

Prognosis

• The prognosis for uncomplicated cases of bacterial vaginosis is generally excellent.
• The prognosis for complicated cases of bacterial vaginosis leading to other infections varies depending on the particular infectious process.

Patient Education

• Educate patients regarding the basic pathophysiology, natural history, and risk factors of the bacterial vaginosis. BV is not considered a sexually transmitted disease, although sexual contact may predispose patients to development of this process in some cases.
• For excellent patient education resources, visit eMedicine's Parasites and Worms Center and Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Trichomoniasis, Birth Control Overview, and Birth Control FAQs.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• For patients presenting with atypical clinical features of bacterial vaginosis, the clinician must be aware of the possibility of a coinfection, such as vaginal candidiasis, trichomoniasis, infection with C trachomatis or N gonorrhoeae, HSV infection, or an alternative diagnosis.
• Provide patients at risk of HIV with HIV counseling and testing.

Special Concerns

• No adequate and well-controlled human trials evaluating teratogenicity of clindamycin or metronidazole in pregnant women have been performed.
• The use of the cream formulation of clindamycin may result in preterm birth.
• Several clinical trials using both preparations in pregnancy have been conducted. The use of metronidazole after the first trimester is considered within the standard of care.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Oct 8, 2008