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Bacterial Vaginosis

Vaginal discharge is a common gynecologic complaint and accounts for half of patient visits to private gynecologists. Vaginitis, or inflammation of the vagina, is usually associated with an increase in vaginal secretions or discharge. Vaginal discharge may be normal or pathologic. Normal or physiologic vaginal discharge, called leukorrhea, is not associated with vulvar discomfort, is usually nonpruritic, has no offensive odor, contains few white cells, and has normal vaginal flora. The predominant organisms comprising normal vaginal flora are lactobacilli, which are gram-positive rods. Normal vaginal secretions have an acidic pH of about 4.0. Common causes of an increase in physiologic discharge are ovulation, pregnancy, and oral contraceptive use. Discharge may also increase before normal menstruation. An abnormal vaginal discharge usually has an offensive odor, often contains many polymorphonuclear leukocytes, has an abnormal vaginal microflora, and is frequently accompanied by dysuria, dyspareunia, and vulvar itching and soreness.
There are many causes, both infectious and noninfectious, for an abnormal vaginal discharge. Extravaginal disease may mimic vaginal discharge. Dermatologic and psychosomatic disorders may result in vaginal complaints. Rectovaginal or vesicovaginal fistulae may result in the passage of either feces or urine through the vagina. Patients with proctitis may have a discharge that simulates a vaginal discharge. Noninfectious causes of vaginal discharge include chemical irritation or allergy from contraceptive foams or feminine hygiene products, a foreign body such as a forgotten vaginal tampon or device used for masturbation, and atrophic vaginitis. The vaginal mucosa in postmenopausal women may be deficient in estrogen, resulting in a thin, scanty discharge that is sometimes accompanied by vulvar soreness and pruritus. The atrophic vaginal mucosa also may become secondarily infected. Vaginal discharge is sometimes seen with gynecologic neoplasms. The discharge may be scanty and tinged with blood.
The majority of cases of vaginal discharge have an infectious cause, and numerous organisms have been implicated. The three most frequent forms of infectious vaginitis are candidal vaginitis, trichomoniasis, and bacterial vaginosis caused by Gardnerella vaginalis and a variety of anaerobes. Neisseria gonorrhoeae rarely infects the adult vagina, and the discharge caused by the gonococcus originates in the endocervix. The discharge passes through the introitus and is perceived by the patient as vaginal discharge. Similarly, chlamydial or herpetic cervicitis may be associated with an excessive cervical discharge, which the patient observes as an abnormal vaginal discharge.
The symptoms of vaginitis are vaginal discharge, dysuria, dyspareunia, and foul vaginal odor. Dysuria can indicate infection at a number of different sites: the urethra (acute urethral syndrome), bladder (cystitis), kidneys (pyelonephritis), vulva and vagina (vulvovaginitis), and cervix (cervicitis). A patient may be able to localize the dysuria as either internal (felt inside the body), indicating urinary tract infection, or external (felt over the vaginal labia as urine is passed), suggesting vaginitis. In a large study of women presenting to a primary care clinic with a complaint of dysuria, vaginitis was found far more often than a urinary tract infection (70% vs. 12%). Therefore, women with dysuria should be asked about symptoms of vaginal discharge and vulvar irritation, as well as the presence of internal or external dysuria.
The most frequent causes of vaginal infection, depending on the population studied, are vulvovaginal candidiasis and bacterial vaginosis. Most of the fungi isolated from patients with vaginitis are Candida albicans. Approximately 10% to 15% of cases are caused by other Candida species, such as Torulopsis glabrata. Although vaginal candidiasis can be transmitted sexually, sexual acquisition is of limited importance; therefore, there is no need to treat asymptomatic male sexual partners of women with vaginal candidiasis. Moreover, patients can continue intercourse during therapy. Predisposing risk factors for vaginal candidiasis are antimicrobials, pregnancy, oral contraceptives, corticosteroids, exogenous hormones, diabetes mellitus, local allergy to perfumes, HIV, and nylon underwear. The data supporting the importance of some of the risk factors, such as oral contraceptives, remain controversial, and further evidence is needed. Host factors must be involved to explain why some women have infrequent episodes of vaginal candidiasis and others suffer from recurrent infections. Rectal colonization with yeasts is often blamed for recurrent vaginal candidiasis, but in one study the rate of relapse was not related to rectal carriage of Candida. The cause of most episodes of recurrent vaginal candidiasis is unknown because the usual predisposing factors are often absent.
As reported for vaginitis of other causes, the clinical features of candidiasis are not distinct enough to permit an accurate etiologic diagnosis. Self-diagnosis is often inaccurate. A curdlike discharge suggests the diagnosis, but a thin discharge occurs as well. The diagnosis can usually be confirmed with a 10% potassium hydroxide preparation or Gram’s-stained vaginal smear. Vaginal pH is normal in patients with candidiasis. The diagnosis, however, is not ruled out by a negative result on wet preparation or Gram’s-stained smear for yeasts. A culture for Candida may be helpful in symptomatic patients when microscopic examination for yeasts is negative. Some 25% to 50% of normal women have yeast as part of their vaginal flora; therefore, for most patients a vaginal culture for Candida is not indicated. The diagnosis is made by microscopic examination, and empiric antifungal therapy should be administered.
Various antifungal agents (clotrimazole, miconazole, terconazole, butoconazole, tioconazole, nystatin, ketoconazole, itraconazole, and fluconazole) are used successfully to treat vulvovaginal candidiasis. Cure rates with the different preparations are similar, but duration of therapy varies. Nystatin is administered intravaginally for 14 days, miconazole for 7 days, and clotrimazole for 3 days. Single-dose intravaginal therapy with clotrimazole also yields comparable results. Oral ketoconazole administered for 3 days produces a similar cure rate, but hepatic toxicity has been reported. A single oral dose of 150 mg of fluconazole is effective and convenient. Women with complicated infections are less likely to respond to short-course therapy and require fluconazole for 10 to 14 days. One study shows that even powdered boric acid (600 mg) in gelatin capsules inserted intravaginally produces cure rates better than 90%. Unfortunately, boric acid capsules are not commercially available and must be prepared by a pharmacist or by the patient. Oral ingestion of yogurt containing Lactobacillus acidophilus or other Lactobacillus preparations may decrease the rate of vaginal candidiasis in comparison with placebo.
Although the various intravaginal preparations can achieve excellent results for an isolated episode of vulvovaginal candidiasis, management of recurrent disease, defined as four or more episodes per year, is a frustrating problem for both patient and clinician. Current therapy has limited value. Use of preparations to decrease Candida in the stool and treatment of the male partner do not affect the recurrence rate. In one controlled test, a 2-week course of oral ketoconazole followed by low-dose ketoconazole (100 mg daily) for 6 months was effective in reducing the rates of recurrent disease. After the prophylaxis was discontinued, the recurrence rates were high. Liver function tests should be obtained monthly for patients receiving long-term ketoconazole. Other drugs for recurrent disease after an initial induction regimen has resulted in negative cultures include fluconazole (100 mg a week) and clotrimazole (500-mg vaginal suppositories once weekly). Further studies are needed to help solve the difficult problems of recurrent vaginal candidiasis.
Trichomonas vaginalis, a flagellate protozoan, is a well-recognized and frequent cause of vaginitis. The organism is usually but not invariably transmitted by sexual intercourse. Trichomoniasis facilitates the transmission of HIV. The textbook description of trichomoniasis as vaginitis with frothy discharge and “strawberry appearance” of the cervix is rarely seen. Trichomoniasis, like vaginitis of other causes, cannot be reliably diagnosed by the clinical presentation. Vaginal pH is increased to about 5.0 to 5.5, as in patients with nonspecific vaginitis. In symptomatic patients, a wet mount of vaginal secretions obtained from the posterior vaginal fornix establishes a diagnosis for about 70% of patients. The wet mount is less sensitive in patients with asymptomatic infections. The culture in which modified Diamond’s medium is used diagnoses 95% of cases, but this technique requires 2 to 7 days. Another useful diagnostic test, called the InPouch system, consists of two chambers—one for wet preparation and the other for culture. Papanicolaou’s smear detects about 70% of infections, depending on the expertise of the cytologist. A test based on monoclonal antibody technology is available for rapid diagnosis; it is a direct immunofluorescence assay having a sensitivity of about 90%. A test in which a DNA probe is used is also available and has a sensitivity of 90%. Secretions for diagnosis should be obtained not from the endocervical canal but from the posterior vaginal fornix.
Both symptomatic and asymptomatic women with trichomoniasis should receive treatment. If trichomoniasis is untreated in pregnancy, there is an increase in premature rupture of the membranes and premature birth. In addition, the regular sexual partners of patients need to be treated to prevent reinfection. A single 2-g dose of metronidazole is highly effective. Male partners can also be treated with a 2-g dose of metronidazole. Alcohol should be avoided for 24 hours after metronidazole is taken. In the first trimester of pregnancy, metronidazole is not recommended, and clotrimazole can be prescribed for intravaginal use, although this drug is less effective than metro-nidazole. Metronidazole can be used in the last two trimesters of pregnancy without adverse effects. A few patients have intractable trichomoniasis, which usually responds to 2 g of metronidazole taken orally for 7 days. Rarely, IV metronidazole is required to treat this infection when a patient cannot tolerate the oral drug. Paromomycin can be used for the rare patients who fail to respond to metronidazole.
Bacterial Vaginosis
Bacterial vaginosis, formerly “nonspecific vaginitis,” accounts for at least 40% of cases of vaginitis. The origin of the syndrome is polymicrobic; causative organisms include G. vaginalis (a small gram-variable coccobacillus) and a variety of anaerobes such as Bacteroides species and Peptococcus species. A curved, gram-variable to gram-negative anaerobic organism (Mobiluncus species) has also been isolated as part of the polymicrobial flora. Confusion has arisen about the taxonomic position of G. vaginalis. The former designations were Haemophilus vaginalis and Corynebacterium vaginalis. Bacterial vaginosis is also associated with a decrease in the lactobacilli that produce hydrogen peroxide.
Features of this diagnosis include a thin, homogeneous vaginal discharge; vaginal pH greater than 4.5; a fishy amine odor after 10% potassium hydroxide is added to a drop of vaginal discharge; vaginal odor resulting from the abnormal amines released; and the presence of clue cells, which are vaginal epithelial cells covered with gram-variable coccobacilli. These cells are noted in 90% of patients with this disease, whereas only 10% of uninfected women have them. A culture for G. vaginalis is invariably positive, but 50% of uninfected persons also have this organism as part of the normal vaginal flora. There is little need, therefore, to obtain a culture to confirm the diagnosis. In addition, aerobic lactobacilli and white cells are generally absent from the vaginal smear. A rapid assay to detect proline aminopeptidase activity in vaginal fluid has a sensitivity of 84% and a specificity of 70%. A DNA probe for G. vaginalis is available for diagnosis but is expensive.
The mode of disease transmission is not clear, and sexual transmission is unproven. Treatment of the male sexual partner usually is not indicated. Studies of sexual transmission found no beneficial effects on cure rates when partners of women with bacterial vaginosis were treated. However, this issue is still controversial, and partners of women with intractable or recurrent disease should be treated. Studies have reported an increased risk for prematurity linked to chorioamnionitis in women with bacterial vaginosis.
Metronidazole is the drug of choice for this disease. Various treatment schedules may be used, including administering 500 mg orally twice daily for 7 days, or a 2-g single dose. There is no difference in cure rates obtained with a single dose of metro-nidazole or with a more prolonged course, but the recurrence rate is higher with single-dose therapy. Clindamycin administered in a dosage of 300 mg twice daily for 7 days is also efficacious. Topical intravaginal treatment with 5 g of 2% clindamycin vaginal cream once daily for 3 days, or 5 g of metronidazole vaginal gel twice a day for 5 days, is also effective. Ampicillin cures about one third of patients and is an alternative, especially in pregnancy, without adverse effects. Asymptomatic women from whom clue cells are obtained on a wet mount do not require therapy except in pregnancy and before elective gynecologic surgery. Future studies are needed to define the natural history of asymptomatic disease, identify complications, develop strategies to manage patients with intractable disease, and discover the best screening approaches and treatment in pregnancy. (N.M.G.)
Ahmed-Jushuf IH, Shahmanesh M, Arya OP. The treatment of bacterial vaginosis with a 3-day course of 2% clindamycin cream: results of a multicentre, double-blind, placebo-controlled trial. Genitourin Med 1995;71:254–256.
Use of 2% clindamycin vaginal cream once nightly for 3 days was effective for bacterial vaginosis.
Amsel R, et al. Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74:14.
Diagnostic criteria for bacterial vaginosis include a vaginal pH greater than 4.5; a fishy odor from the vaginal discharge with the addition of 10% potassium hydroxide; clue cells; and a thin, homogeneous vaginal discharge.
Brunham RC, et al. Mucopurulent cervicitis—the ignored counterpart in women of urethritis in men. N Engl J Med 1984;311:1.
Illustration of mucopurulent cervicitis caused by Chlamydia.
DeMeo LR, et al. Evaluation of a deoxyribonucleic acid probe for the detection of Trichomonas vaginalis in vaginal secretions. Am J Obstet Gynecol 1996;174:1339– 1342. The DNA probe for trichomoniasis had a sensitivity of about 90%.
Fouts AC, Kraus SJ. Trichomonas vaginalis: reevaluation of its clinical presentation and laboratory diagnosis. J Infect Dis 1980;141:137.
A frothy discharge is not pathognomonic for trichomoniasis.
Geiger AM, Foxman B. Risk factors for vulvovaginal candidiasis: a case-control study among university students. Epidemiology 1996;7:182–187.
Risk factors for vaginal candidiasis included age under 24 years, black race, diagnosis of Candida vaginitis in the prior year, and receptive oral sex.
Greaves WL, et al. Clindamycin versus metronidazole in the treatment of bacterial vaginosis. Obstet Gynecol 1988;72:799.
Oral clindamycin is an alternative drug for bacterial vaginosis.
Hauth JC, et al. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N Engl J Med 1995;333:1732–1736.
In pregnant women with bacterial vaginosis, use of erythromycin plus metronidazole decreased the rates of prematurity.
Heine RP, et al. Polymerase chain reaction analysis of distal vaginal specimens: a less invasive strategy for detection of Trichomonas vaginalis. Clin Infect Dis 1997; 24:985–987.
Polymerase chain reaction testing had a yield of 92% for trichomoniasis when a swab was inserted about 1 inch into the vagina.
Hilton E, et al. Ingestion of yogurt containing Lactobacillus acidophilus as prophylaxis for candidal vaginitis. Ann Intern Med 1992;116:353.
Daily ingestion for 6 months of 8 oz of yogurt with Lactobacillus acidophilus decreased the rate of vaginal candidal colonization and infection. (See also Drutz DJ. Lactobacillus prophylaxis for Candida vaginitis. Ann Intern Med 1992;116:419.)
Joesoef MR, Schmid GP. Bacterial vaginosis: review of treatment options and potential clinical indications for therapy. Clin Infect Dis 1995;20 (Suppl 1):S72–S79.
Oral metronidazole (500 mg twice daily for 7 days) is the drug of choice for bacterial vaginosis.
Kent HL. Epidemiology of vaginitis. Am J Obstet Gynecol 1991;165:1168.
The incidence of candidal infection has increased during the past decade, with an increased percentage of non-albicans candidal strains, such as C. tropicalis and C. glabrata.
Komaroff AL, et al. Management strategies for symptoms of urinary and vaginal infections. Arch Intern Med 1978;138:1069.
Internal dysuria suggests that the patient has a urinary tract infection, and external dysuria favors a diagnosis of vaginitis.
Krieger JN, et al. Diagnosis of trichomoniasis: comparison of conventional wet-mount examination with cytologic studies, cultures, and monoclonal antibody staining of direct specimens. JAMA 1988;259:1223.
Various methods for the diagnosis of trichomoniasis are compared. The wet-mount examination and Papanicolaou’s smear had a sensitivity of about 60%. A false-positive smear was noted in 31% of patients and needs to be confirmed by a wet-mount examination. (See also Lossick JG. The diagnosis of vaginal trichomoniasis. JAMA 1988;259:1230.)
Lossick JG, Kent HL. Trichomoniasis: trends in diagnosis and management. Am J Obstet Gynecol 1991;165:1217.
Diagnostic methods include saline wet preparation, Papanicolaou’s smear, culture, direct immunofluorescence assay, direct enzyme immunoassay, and latex agglutination test. The sensitivities of the saline wet-mount examination and Papanicolaou’s smear are about 60%.
Lugo-Miro VI, Green M, Mazur L. Comparison of different metronidazole therapeutic regimens for bacterial vaginosis: a metaanalysis. JAMA 1992;268:92.
There is no difference between the cure rates of patients with bacterial vaginosis treated with metronidazole as a 2-g single dose, a 2-g single dose given for 2 days, 400 mg three times daily for 5 days, or 500 mg twice daily for 7 days.
Milne JD, Warnock DW. Effect of simultaneous oral and vaginal treatment on the rate of cure and relapse in vaginal candidiasis. Br J Vener Dis 1979;55:362.
Relapse of vaginal candidiasis was unrelated to rectal carriage of yeast.
Nyirjesy P, et al. Over-the-counter and alternative medicines in the treatment of chronic vaginal symptoms. Obstet Gynecol 1997;90:50–53.
The most frequent alternative medicines used were acidophilus products or yogurt. Most of the yogurt products lack hydrogen peroxide-producing Lactobacillus strains that might be of benefit.
Paterson BA, et al. The tampon test for trichomoniasis: a comparison between conventional methods and a polymerase chain reaction for Trichomonas vaginalis in women. Sex Transm Infect 1998;74:136–139.
Polymerase chain reaction testing on a tampon specimen was useful for diagnosis of trichomoniasis.
Petrin D, et al. Clinical and microbiological aspects of Trichomonas vaginalis. Clin Microbiol Rev 1998;11:300–317.
Review. The best diagnostic assay uses the InPouch system, which consists of a two-chambered bag—one for a wet preparation and the other for culture.
Pheifer TA, et al. Role of Haemophilus vaginalis and treatment with metronidazole. N Engl J Med 1978;298:1429.
Metronidazole is highly effective in an oral dose of 500 mg twice daily.
Reef SE, et al. Treatment options for vulvovaginal candidiasis, 1993. Clin Infect Dis 1995;20(Suppl 1):S80–S90.
Review of therapy for vaginal candidiasis.
Schaaf VM, Perez-Stable EJ, Borchardt K. The limited value of symptoms and signs in the diagnosis of vaginal infections. Arch Intern Med 1990;150:1929.
An etiology of vaginitis was identified in only half of the patients. Symptoms did not differ for the three diagnoses.
Schmitt C, Sobel JD, Meriwether C. Bacterial vaginosis: treatment with clindamycin cream versus oral metronidazole. Obstet Gynecol 1992;79:1020.
Cure rate with clindamycin vaginal cream was 72%. No data exist regarding the use of clindamycin cream in pregnancy.
Sobel JD. Recurrent vulvovaginal candidiasis: a prospective study of the efficacy of maintenance ketoconazole therapy. N Engl J Med 1986;315:1455.
Prophylactic oral ketoconazole (100 mg daily for 6 months) was effective in preventing recurrent vaginal candidiasis. Six months after stopping therapy, half of the patients had recurrence.
Sobel JD. Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin Infect Dis 1992;14(Suppl 1):S148.
Supressing a gastrointestinal focus with nystatin and treating sexual partners does not prevent recurrent vaginal candidiasis.
Sobel JD. Vaginitis. N Engl J Med 1997;337:1896–1903.
Sobel JD, Chaim W. Treatment of Torulopsis glabrata vaginitis: retrospective review of boric acid therapy. Clin Infect Dis 1997;24:649–652.
In patients with Torulopsis (Candida) glabrata vaginitis who fail azole therapy, vaginal boric acid may be effective.
Sobel JD, et al. Single oral dose fluconazole compared with conventional clotrimazole topical therapy of Candida vaginitis. Am J Obstet Gynecol 1995;172:1263–1268.
A single oral dose of fluconazole (150 mg) was effective for vaginal candidiasis.
Sobel JD, et al. Vulvovaginal candidiasis: epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998;178:203–211.
Spence MR, et al. The minimum single oral metronidazole dose for treating trichomoniasis: a randomized, blinded study. Obstet Gynecol 1997;89:699–703.
The minimum effective dose of metronidazole was 1.5 g.
Spiegel CA. Bacterial vaginosis. Clin Microbiol Rev 1991;4:485.
Review of diagnosis and treatment.
Thomason JL, Gelbart SM, Scaglione NJ. Bacterial vaginosis: current review with indications for asymptomatic therapy. Am J Obstet Gynecol 1991;165:1210.
More than 50% of women with bacterial vaginosis are asymptomatic.
Van Slyke KK, Michel VP, Rein MF. Treatment of vulvovaginal candidiasis with boric acid power. Am J Obstet Gynecol 1981;141:145.
Boric acid powder (600 mg) in a gelatin capsule inserted intravaginally at bedtime had a 91% cure rate.
Winceslaus SJ, Calver G. Recurrent bacterial vaginosis—an old approach to a new problem. Internat J STD AIDS 1996;7:284–287.
Hydrogen peroxide (3%) used as a single vaginal wash was effective for bacterial vaginosis.
Wolner-Hanssen P, et al. Clinical manifestations of vaginal trichomoniasis. JAMA 1989;261:571.
Excellent review of the clinical manifestations. Colpitis macularis (strawberry cervix) had a sensitivity of 44% with an odds ratio of 241; a frothy discharge had a sensitivity of 8% with an odds ratio of 21. Overall, the sensitivity of the symptoms and signs of trichomoniasis is low.


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