vaginitis

INTRODUCTION Vaginitis is the general term for disorders of the vagina caused by infection,
inflammation, or changes in the normal vaginal flora. Symptoms include vaginal discharge, odor,
pruritus, and/or discomfort. These symptoms are extremely common and frequently lead to selfdiagnosis and therapy [1]. In a telephone survey of random women in the United States, 8 percent
of Caucasian women and 18 percent of African American women reported an episode of vaginal
symptoms of any severity in the previous year [2]. A healthcare professional was consulted in 55
and 83 percent of cases, respectively, and most women purchased an over-the-counter antifungal
preparation to treat their symptoms, whether or not they saw a physician.
CAUSES OF VAGINITIS The most common causes of vaginal discharge, odor,
pruritus, and/or discomfort are bacterial vaginosis, candida vulvovaginitis, and trichomoniasis.
These disorders account for over 90 percent of cases [3].
(See "Bacterial vaginosis".)
(See "Candida vulvovaginitis".)
(See "Trichomoniasis".)
Less common causes of these symptoms include vaginal atrophy/atrophic vaginitis, cervicitis,
foreign body, irritants and allergens, and several rarer entities, including some systemic medical
disorders.
PATHOGENESIS The nonkeratinized stratified squamous epithelium of the vagina in
premenopausal women is rich in glycogen. Glycogen from sloughed cells is the substrate for
Dderlein's lactobacilli, which convert glucose into lactic acid, thereby creating an acidic vaginal
environment (pH 4.0 to 4.5). This acidity helps maintain the normal vaginal flora and inhibits growth
of pathogenic organisms. Disruption of the normal ecosystem can lead to conditions favorable for
development of vaginitis. Some of these potentially disruptive factors include phase of the
menstrual cycle, sexual activity, contraceptive choice, pregnancy, foreign bodies, estrogen level,
sexually transmitted diseases, and use of hygienic products or antibiotics.
PATIENT PRESENTATION Women with vaginitis typically present with one or more of the
following vulvovaginal symptoms:
Change in the volume, color, or odor of vaginal discharge
Pruritus
Burning
Irritation

Erythema
Dyspareunia
Spotting
Dysuria
Vaginal discharge is a prominent symptom of vaginitis, but may be difficult to distinguish from
normal vaginal discharge. In reproductive aged women, normal vaginal discharge consists of 1 to 4
mL fluid (per 24 hours), which is white or transparent, thick or thin, and mostly odorless. This
physiologic discharge is formed by mucoid endocervical secretions in combination with sloughing
epithelial cells, normal vaginal flora, and vaginal transudate. The discharge may become more
noticeable at times (physiological leukorrhea), such as at midmenstrual cycle close to the time of
ovulation or during pregnancy or use of estrogen-progestin contraceptives. Diet, sexual activity,
medication, and stress can also affect the volume and character of normal vaginal discharge.
Although normal discharge may be yellowish, slightly malodorous, and accompanied by mild
irritative symptoms [4], it is not accompanied by pruritus, pain, burning or significant irritation,
erythema, local erosions, or cervical or vaginal friability. The absence of these signs and symptoms
distinguishes it from discharge related to a pathological process, such as vaginitis or cervicitis.
(See 'Management of physiological leukorrhea' below.)
GENERAL PRINCIPLES Laboratory documentation of the etiology of vaginitis is mandatory
before initiating therapy, given the nonspecific nature of the symptoms [5]. Diagnostic testing
enables targeted treatment, increases therapeutic compliance, and increases the likelihood of
partner notification [6]. Empiric therapy based on history and physical examination alone should be
avoided because of frequent misdiagnosis and inappropriate therapy. However, 25 to 40 percent of
patients with genital symptoms do not have a specific cause identified after initial diagnostic testing
[7].
The three main steps in the evaluation of women with symptoms of vaginitis are:
Obtain a history and perform a physical examination. (See 'Physical examination' below
and 'History' below.)
Test for bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis since these
disorders account for over 90 percent of vaginitis in premenopausal women and can be
diagnosed by pH testing, microscopy, and/or culture (or rapid antigen and nucleic acid
amplification tests) [3]. (See 'Diagnostic studies' below.)
If this evaluation does not lead to a diagnosis, then evaluate for less common and rare
causes of vaginitis. (See 'Women without a diagnosis after the initial evaluation' below.)
Patients who continue to exhibit symptoms and/or have positive tests for sexually transmitted
infections after treatment are most likely to have been re-infected by their sexual partner [7].

DIAGNOSTIC EVALUATION None of the findings from the history allows a definitive diagnosis
since there is considerable overlap in symptoms among the different etiologies of vaginitis [4,8].
Thus, all women with suspected vaginitis should undergo a physical examination and some
diagnostic studies.
The history often suggests a particular diagnosis (table 1), which must be confirmed in the office by
examination of vaginal secretions and, if necessary, culture (or rapid antigen and nucleic acid
amplification tests). A literature review concluded that the initial office evaluation (history and
physical examination; pH, wet mount microscopy, and whiff test of vaginal discharge) correctly
diagnosed 60 percent of candidal vulvovaginitis, 70 percent of trichomoniasis, and 90 percent of
bacterial vaginosis [9].

History The key questions on history are to determine the patients symptoms. If discharge is
present, what is the quantity, color, consistency, and odor? Is there burning or other discomfort?
Vaginal bleeding? Dysuria or dyspareunia?

The severity of symptoms correlates with the extent of inflammation. Candida vulvovaginitis often
presents with marked inflammatory symptoms (pruritus and soreness), but scant discharge (thick,
white, odorless, and curd-like). In contrast, bacterial vaginosis is associated with only minimal
inflammation and minimal irritative symptoms, but the thin, gray or yellow, malodorous discharge is
a prominent complaint. Trichomoniasis is characterized by purulent, malodorous, thin discharge,
which may be accompanied by burning, pruritus, dysuria, frequency, and/or dyspareunia. The vulva
is affected by candidiasis and sometimes by trichomoniasis, but not by bacterial vaginosis. Vaginal
dryness and dyspareunia are common features of atrophic vaginitis. Symptoms of candidal
vulvovaginitis often occur in the premenstrual period, while symptoms of trichomoniasis often occur
during or immediately after the menstrual period.
However, as discussed above, none of the findings from the history allows a definitive diagnosis
since there is considerable overlap in symptoms among the different etiologies of vaginitis [4,8].
Physical examination The physical examination is focused upon the degree of vulvovaginal
inflammation and the characteristics of the vaginal discharge, as well as the presence of lesions or
foreign bodies. Other potentially significant findings include signs of cervical inflammation and pelvic
or cervical motion tenderness.
The vulva usually appears normal in bacterial vaginosis, whereas erythema, edema, or
fissures suggest candidiasis, trichomoniasis, or dermatitis. Atrophic changes are caused by
hypoestrogenemia, and suggest the possibility of atrophic vaginitis. Changes in vulvovaginal
architecture (eg, scarring) may be caused by a chronic inflammatory process, such as erosive
lichen planus, as well as lichen sclerosis, or mucous membrane pemphigoid, rather than
vaginitis.
Speculum examination may reveal a lesion.

A foreign body (eg, retained tampon) is easily detected and is often associated with
vaginal discharge, intermittent bleeding or spotting, and/or an unpleasant odor due to
inflammation and secondary infection. Removal of the foreign body is generally adequate
treatment. Antibiotics are rarely indicated.
Vaginal warts are skin-colored or pink, and range from smooth flattened papules to a
verrucous, papilliform appearance (picture 1). When extensive, they can be associated
with vaginal discharge, pruritus, bleeding, burning, tenderness, and pain.
(See "Condylomata acuminata (anogenital warts) in adults" and"Treatment of vulvar and
vaginal warts".)
Granulation tissue or surgical site infection can cause vaginal discharge after
hysterectomy or after childbirth.
Necrotic or inflammatory changes associated with malignancy in the lower or upper
genital tract can result in vaginal discharge; spotting is more common in this setting than
in infectious vaginitis.
The presence of multifocal rounded macular erythematous lesions (like a spotted rash
or bruise), purulent discharge, and tenderness suggests erosive vulvovaginitis, which
can be caused by trichomoniasis or one of several noninfectious inflammatory etiologies
[10].
The characteristics of the vaginal discharge may help distinguish the type of infection, if
present (table 2). Trichomoniasis is classically associated with a greenish-yellow purulent
discharge; candidiasis with a thick, white, adherent, "cottage cheese-like" discharge; and
bacterial vaginosis with a thin, homogeneous, "fishy smelling" gray discharge.
Inflammation and/or necrosis related to malignancy of the lower or upper genital tract can
result in watery, mucoid, purulent, and/or bloody vaginal discharge.
However, the appearance of the discharge is unreliable and should never form the basis for
diagnosis [4].
Cervical inflammation with a normal vagina is suggestive of cervicitis, rather than vaginitis.
The cervix in women with cervicitis is usually erythematous and friable, with a mucopurulent
discharge (picture 2). (See "Acute cervicitis".)
Cervical erythema in cervicitis should be distinguished from ectropion, which represents the
normal physiologic presence of endocervical glandular tissue on the exocervix. Ectropion is
more common in women taking estrogen-progestin contraceptives and during pregnancy.
Ectropion may increase the volume of normal vaginal discharge. (See "Congenital cervical
anomalies and benign cervical lesions", section on 'Ectropion'.)
Vesicovaginal and rectovaginal fistulas are rare, can be hard to detect, and are a source of
chronic vaginal discharge. At-risk patients include those who are postpartum,
posthysterectomy, post surgery for prolapse, or have a history of inflammatory bowel disease

or radiation therapy to the pelvis. (See "Rectovaginal and anovaginal fistulas" and "Urogenital
tract fistulas in women".)
Bimanual examination may reveal pelvic or cervical motion tenderness suggestive of PID.
(See "Clinical features and diagnosis of pelvic inflammatory disease".)
Diagnostic studies Examining the vaginal discharge for pH and fishy amine odor, and by
microscopy, may lead to a definitive diagnosis (table 2) [4].
Vaginal pH Measurement of vaginal pH is the single most important finding that drives the
diagnostic process and should always be determined. A pH test stick (or pH paper if available) is
applied for a few seconds to the vaginal sidewall (to avoid contamination by blood, semen, or
cervical mucus which pool in the posterior fornix and distort results). Alternatively, the vaginal
sidewall can be swabbed with a dry swab and then the swab rolled onto pH paper (if available). The
pH of the specimen is stable for about two to five minutes at room temperature. The swab should
not be pre-moistened, as the moistening liquid can affect pH.
Narrow range pH paper (4.0 to 5.5) is easier to interpret than broad range paper (4.5 to 7.5). An
elevated pH in a premenopausal woman suggests infections such as bacterial vaginosis (pH>4.5)
or trichomoniasis (pH 5 to 6), and helps to exclude candida vulvovaginitis (pH 4 to 4.5).
The pH of the normal vaginal secretions in premenopausal women is 4.0 to 4.5 because these
women have relatively high estrogen levels. Under the influence of estrogen, the normal vaginal
epithelium cornifies and produces glycogen, which is the substrate for lactic acid production by
lactobacilli. In premenarchal and postmenopausal women in whom estrogen levels are low, the pH
of the normal vaginal secretions is 4.7. The higher pH is due to less glycogen in epithelial cells,
reduced colonization of lactobacilli, and reduced lactic acid production. Thus measurement of pH for
diagnosis of bacterial vaginosis, trichomoniasis, or candidiasis is less useful at the extremes of age.
(See "Clinical manifestations and diagnosis of vaginal atrophy".)
Vaginal pH may be altered (usually to a higher pH) by contamination with lubricating gels, semen,
douches, and intravaginal medications. In pregnant women, leakage of amniotic fluid raises vaginal
pH.
Microscopy
Saline wet mount Vaginal discharge is generally sampled with a plastic or
wood vaginal/cervical scraper or a cotton-tipped swab. The sample of vaginal discharge is mixed
with one to two drops of 0.9 percent normal saline solution at room temperature on a glass slide.
Cover slips are then placed on the slides, which are examined under a microscope at low and high
power. Microscopy should be performed within 10 to 20 minutes of obtaining the sample to reduce
the possibility of loss of motility of any trichomonads. (See "Trichomoniasis".)
Microscopic examination of normal vaginal discharge reveals a predominance of squamous
epithelial cells, rare polymorphonuclear leukocytes (PMNs), and Lactobacillusspecies morphotype
(table 2). The primary goal of the examination is to look for candidal buds (picture 3) or hyphae

(picture 4), motile trichomonads (picture 5), epithelial cells studded with adherent coccobacilli (clue
cells; (picture 6 and picture 7)), and increased numbers of PMNs. Clue cells may be accompanied
by Mobiluncus species (movie 1).
Excess PMNs without evidence of yeast, trichomonads, or clue cells suggest cervicitis. (See "Acute
cervicitis".)
Potassium hydroxide wet mount The addition of 10 percent potassium hydroxide (KOH) to the
wet mount of vaginal discharge destroys cellular elements, thus it is helpful for identifying hyphae
and budding yeast for the diagnosis of candidal vaginitis (picture 3 and picture 4). (See "Candida
vulvovaginitis".)
Amine test Smelling ("whiffing") the slide immediately after applying KOH is useful for detecting
the fishy (amine) odor of bacterial vaginosis (see "Bacterial vaginosis", section on 'Diagnosis').
Options when microscopy is not available If microscopy is not available, commercial
diagnostic testing methods (eg, rapid antigen and nucleic acid amplification tests) are used for
confirming the clinical suspicion of bacterial vaginosis or trichomonas vaginitis. (See "Bacterial
vaginosis", section on 'Commercial tests'and "Trichomoniasis", section on 'Rapid antigen, DNA
hybridization probe, and nucleic acid amplification tests'.)
None of these methods are sufficiently sensitive for diagnosis of Candida species; a culture for
Candida species must be obtained. (See "Candida vulvovaginitis", section on 'Office diagnosis'.)
Vaginal culture If microscopy is negative, culture for Candida species or Trichomonas vaginalis
(the choice is dictated by the clinical findings) is important because microscopy is not sufficiently
sensitive to exclude these diagnoses in symptomatic patients. A diagnostic test card using nucleic
acid amplification (NAAT), if available, is an acceptable alternative to culture if trichomoniasis is
suspected. In one study, the sensitivity of microscopy for diagnosis of Candida species and
Trichomonas vaginalis was only 22 and 62 percent, respectively, using Grams stain as the standard
[5]. Sensitivity of microscopy is 50 percent compared to a standard of NAAT for trichomoniasis or
culture for Candida species.
Bacterial cultures are rarely indicated in women with vaginal discharge. In fact, they are frequently
misleading since a large variety of bacterial species colonize the vagina and are not vaginal
pathogens [11]; identification of these bacteria may lead to unnecessary antibacterial therapy. Apart
from Group A streptococcus, a clear causal relationship between any bacteria and vaginitis has not
been established in adults.
Cervical culture A diagnosis of cervicitis, typically due to Neisseria gonorrhoeae or Chlamydia
trachomatis, must always be considered in women with purulent cervical discharge since women
with this disorder may go on to develop PID and its potential complications. Any women with new or
multiple sexual partners, a symptomatic sexual partner, or an otherwise unexplained cervical or
vaginal discharge that contains a high number of PMNs should be tested for the presence of these
organisms, by culture or an alternative sensitive test. (See "Acute cervicitis".)

WOMEN WITHOUT A DIAGNOSIS AFTER THE INITIAL EVALUATION As discussed above, 25

to 40 percent of patients with genital symptoms do not have a specific cause identified on initial
diagnostic evaluation [7].
General approach Exclusion of the three common infectious causes of vaginitis, Candida
vaginitis, bacterial vaginosis, and trichomoniasis, cannot be accomplished by history and physical
examination only; all require specific diagnostic tests, as described above and in the topics on each
infection. (See "Candida vulvovaginitis" and"Bacterial vaginosis" and "Trichomoniasis".)
The following principles reflect the general approach to women in whom Candida vaginitis, bacterial
vaginosis, and trichomoniasis have been ruled out:
If the patient had minimal symptoms at the time of initial evaluation and the evaluation was
nondiagnostic, it should be repeated at a second visit when she is symptomatic.
Avoid empiric blind therapy, which often aggravates symptoms
Determine vaginal pH, as it guides differential diagnosis:
If pH is increased, consider non-infectious causes of vaginal symptoms, such as vaginal
atrophy, atrophic vaginitis, erosive lichen planus, lichen sclerosus, desquamative
inflammatory vaginitis, and pemphigoid syndromes
If pH is normal, the vagina is likely to be normal with normal microbiome, so focus on
the most common vulvar and external causes of vulvovaginal symptoms, such as contact
or irritant dermatitis, seborrheic or eczematoid dermatitis, and psoriasis.
Group A streptococcal vaginitis is associated with a normal or mildly increased pH, but
this is a rare disease
Obtain information on the duration of symptoms (acute versus chronic disease), site of
symptoms (vulva versus vagina), and whether there has been a recent change in sexual
partner, as this information is also helpful in forming a differential diagnosis.
Detailed history The following information from a detailed history may be helpful:
Estrogen status - Is the woman menopausal or otherwise hypoestrogenic? Atrophic
vaginitis is a common cause of vaginitis in hypoestrogenic women. In premenopausal women,
hypoestrogenic settings include the postpartum period, lactation, and during administration of
antiestrogenic drugs (and sometimes with low estrogen levels related to contraceptives).
Menopausal women receiving hormone therapy may not have adequate estrogen levels for
vaginal health and thus remain prone to atrophic vaginitis. (See "Clinical manifestations and
diagnosis of vaginal atrophy".)
Acuity and timing of symptoms - Are the symptoms acute, chronic, or recurrent? An acute
process is likely to have an infectious etiology; a chronic process is more likely from

inflammation unrelated to infection. If the woman has had recurrent episodes of vaginitis, look
up the results of past diagnostic testing, the type of therapy she received, and her response to
this therapy.
Associated symptoms - Does the patient have pelvic pain or systemic symptoms (eg, fever,
nausea)? Pelvic pain is suggestive of pelvic inflammatory disease (PID) and suprapubic pain
is suggestive of cystitis; both are rare with vaginitis. The common causes of vaginitis are not
associated with systemic symptoms. (See"Clinical features and diagnosis of pelvic
inflammatory disease" and "Acute uncomplicated cystitis and pyelonephritis in women".)
Sexual practices - What are the patients sexual practices? What is the gender of her sex
partner? Women who have sex with women are at increased risk of bacterial vaginosis. Has
there been exposure to a new sexual partner? A new sexual partner increases the risk of
acquiring sexually transmitted infections such as Trichomonas vaginalis, or cervicitis related to
Neisseria gonorrhoeae or Chlamydia trachomatis. Is there a history of sexually transmitted
infection? (See "Screening for sexually transmitted infections".)
Medication history - What medications (prescription and nonprescription) are being used?
Antibiotics predispose to candidal vulvovaginitis; estrogen-progestin contraceptives can
increase physiologic discharge; pruritus and burning unresponsive to antifungal agents may
be due to vulvovaginal dermatitis. (See "Dermatitis of the vulva".)
Hygienic practices - What are the patient's hygienic practices? Mechanical, chemical, or
allergic irritation may cause vulvovaginal symptoms (pruritus, burning) mistakenly attributed to
an infectious source. Vaginal symptoms can result from irritants (eg, scented panty liners,
spermicides, povidone-iodine, soaps and perfumes, and some topical drugs) and allergens
(eg, latex condoms, topical antifungal agents, seminal fluid, chemical preservatives) that
produce acute and chronic hypersensitivity reactions, including contact dermatitis. For women
from the developing world, it is important to ask about vaginal practices using traditional
products and medicines, as these can have adverse effects [12].
Careful assessment of the woman's personal practices is the best way to detect potential
irritants and allergens in her environment and habits unhealthy for the vulvar skin.
Patient symptom/contact diaries may be helpful. (See "Dermatitis of the vulva".)
Medical history - Does the patient have a history of an oral mucosal, ocular, cutaneous, or
systemic disease that could affect the vulvovaginal area? For example, herpes simplex virus
and Behets syndrome can cause vulvovaginal ulcers. Women with diabetes are prone to
vulvovaginal candidiasis. Women with human immunodeficiency virus (HIV) are prone to
vaginal infections (see "HIV and women" and "HIV and women", section on 'Clinical
manifestations in women'). After transplantation, graft versus host disease can cause vaginal
irritation, discharge, ulceration, and stenosis [13,14]. Stevens-Johnson syndrome and toxic
epidermal necrolysis have potentially severe vulvovaginal sequelae [15].

Surgical history - Has the patient had recent transvaginal surgery or repair of perineal
lacerations from childbirth? Vaginal symptoms may be related to a foreign body, bacterial
infection, or granulation tissue.
Irritants and allergens Vaginal discharge can result from irritants (eg, scented panty liners,
spermicides, povidone-iodine, soaps and perfumes, and some prescription and nonprescription
topical medications) and allergens (eg, latex condoms, topical antifungal agents, seminal fluid,
chemical preservatives) that produce acute and chronic hypersensitivity reactions, including contact
dermatitis. Women from the developing world may have vaginal practices or use traditional products
and medicines that have adverse effects [12].
Diagnosis and management involve identifying and eliminating the offending agent by taking a
thorough history and systematically removing potential irritants and allergens from the urogenital
environment. Patient symptom/contact diaries may be helpful. Corticosteroid therapy is indicated to
control inflammation and relieve symptoms. We use a medium potency fluorinated topical steroid
two to three times per day, as needed, until symptoms resolve (table 3). (See "Overview of
dermatitis", section on 'Allergic contact dermatitis' and "Overview of dermatitis", section on 'Irritant
contact dermatitis' and "General principles of dermatologic therapy and topical corticosteroid use".)
Menopausal women
Atrophic vaginitis Menopausal women should be evaluated for atrophic vaginitis, which is a
common diagnosis in this age group. Nonspecific signs and symptoms include a watery, white or
yellow, and malodorous discharge; vaginal burning or irritation; dyspareunia; and urinary symptoms.
Physical findings include thinning of the vaginal epithelium, loss of elasticity, loss of rugae, pH 5,
vaginal erosions, and cervicovaginal friability. (See "Clinical manifestations and diagnosis of vaginal
atrophy".)
The wet mount is nonspecific, as similar findings occur in other inflammatory vaginal conditions. It
shows parabasal cells, many polymorphonuclear leukocytes (PMNs), no lactobacilli, with or without
background bacteria. Parabasal cells are immature squamous epithelial cells that are rounded and
have a large nucleus-to-cytoplasm ratio; in contrast, mature squamous epithelial cells are larger,
cuboidal, with a smaller nucleus-to-cytoplasm ratio, and sometimes folded. The presence of
epithelial cells rather than parabasal cells and premenopausal status helps to distinguish bacterial
vaginosis from atrophic vaginitis.
Symptomatic response to topical estrogen therapy, which restores the vaginal epithelium, supports
the diagnosis. Antibiotics are not needed. (See "Treatment of vaginal atrophy", section on 'Vaginal
estrogen therapy'.)
Intraepithelial neoplasia and cancer The following disorders are more common in menopausal
women:
Vaginal intraepithelial neoplasia can present with vaginal discharge and/or postcoital
spotting, although patients are usually asymptomatic. (See "Vaginal intraepithelial neoplasia".)

Vulvar intraepithelial neoplasia may cause vulvar pruritus (see 'Pruritus, with a negative
Candida culture' below).
Fallopian tube cancer may present with a serosanguineous vaginal discharge and pelvic pain
(see 'Serosanguinous discharge and pelvic pain' below).
Pruritus, with a negative Candida culture Pruritus can occur anywhere in the lower genital
tract: the vagina, vestibule, vulva, perineum, or perianal area. It may be unilateral or bilateral. Often
women are unable to localize the site or source. Infrequent, transient, mild

mild vulvovaginal pruritus is relatively common and may be normal. Evaluation is indicated in
women with persistent, chronic, or severe pruritus.
The differential diagnosis is vast and includes both infectious and non-infectious causes.
Noninfectious etiologies are more common: contact dermatitis, either allergic or chemical-induced
irritative dermatitis, is the most common noninfectious etiology. Allergens/irritants include soaps,
creams, microbicides, toilet paper, detergents, and sanitary pads. (See "Dermatitis of the vulva".)
Vulvar dermatoses also account for a substantial proportion of noninfectious cases and include
lichen sclerosus, lichen planus, and lichen simplex chronicus. (See"Vulvar lesions: Differential
diagnosis based on morphology".) Other common skin conditions that may present with external
pruritus include psoriasis, eczema, and seborrheic dermatitis. Vulvar pruritus is the most common
complaint among symptomatic women with vulvar intraepithelial neoplasia; other presentations
include a visible lesion, a palpable abnormality, perineal pain or burning, or dysuria. (See "Vulvar
intraepithelial neoplasia".)
Candida is the most common infectious cause of vulvovaginal pruritus, followed by trichomoniasis
and, uncommonly, bacterial vaginosis.
Evaluation of women with pruritus involves taking a detailed history, which often takes a
considerable amount of time, and performing a thorough physical examination, with laboratory tests
guided by clinical findings. Treatment often begins with a local drug holiday, ie, removing potential
causes of pruritus from daily life. Empiric drug therapy should be avoided. Targeted drug therapy is
administered when a specific cause is identified.
Cytolytic vaginosis Cytolytic vaginosis refers to a rare syndrome of vaginal hyperacidity due to
overgrowth of lactobacilli, although the existence of this entity is controversial. It is characterized by
pruritus, dyspareunia, vulvar dysuria, and cyclical increase in symptoms during the luteal phase
[16,17].

Diagnostic criteria include presence of white vaginal discharge, pH between 3.5 and 4.5, Gram's
stain showing overgrowth of lactobacilli, paucity of white blood cells, evidence of cytolysis (bare
nuclei, shreds of cytoplasm), and exclusion of candidal infection by culture.
Sodium bicarbonate douches have been used for treatment. A solution of one rounded teaspoon of
sodium bicarbonate in 600 mL of water is used for irrigating the vagina, once per day for 7 to 14
days. There are no data to support longer courses of therapy.
Acute onset of purulent discharge and pain Group A streptococcus (Streptococcus pyogenes
[GAS]) is an uncommon cause of vulvovaginitis [18,19]. In one series of almost 7000 pregnant
women, only 0.03 percent were colonized with GAS [18]. GAS vulvovaginitis typically occurs in
prepubertal girls and in mothers whose children suffer from active GAS infection or who serve as
GAS carriers. Carriage or exposure to a carrier is an important source of recurrent GAS infection.
GAS can colonize and be transmitted from skin (especially in individuals with chronic dermatological
conditions), nasopharynx, and the gastrointestinal tract (including the perianal area) [20].
Clinical features include acute onset of frankly purulent discharge accompanied by pruritus,
soreness and irritation, erythema, labial edema, and possibly dysuria from burning of the skin with
voiding. Microscopy of the discharge reveals a marked increase in PMNs and Gram's stain shows
chains of gram-positive cocci.
Penicillin treatment after confirmation of the diagnosis by culture rapidly leads to cure. We use
Penicillin VK 500 mg four times daily for 10 to 14 days or clindamycincream 2% vaginally for 7 to 10
days.
Serosanguinous discharge and pelvic pain Women with fallopian tube carcinoma often
present in the fifth or sixth decades with vague complaints, although the incidence of this cancer is
very low. The type and frequency of so-called "classic" symptoms and signs associated with this
malignancy are: serosanguineous vaginal discharge (50 to 60 percent), pelvic pain (30 to 50
percent), and a pelvic mass (12 to 61 percent); however, the full triad (Latzko's triad) is noted in
fewer than 15 percent of patients. Hydrops tubae profluens, which refers to intermittent discharge of
clear or blood-tinged fluid spontaneously or on pressure followed by shrinkage of the adnexal mass,
has been described as pathognomonic of the disease. (See "Epithelial carcinoma of the ovary,
fallopian tube, and peritoneum: Clinical features and diagnosis", section on 'Subacute
presentation'.)
Chronic introital pain as a primary symptom Vestibulodynia refers to pain on penetration of
the introitus and tenderness provoked by focal vestibular pressure. These symptoms should be
present for at least three to six months and other causes of vestibular pain, such as vaginitis, should
be excluded before making the diagnosis. Vaginal discharge and vaginal inflammation are typical
features of vaginitis, but are not part of the clinical spectrum of vestibulodynia. Candidal
vulvovaginitis may mimic localized, provoked vulvodynia, and may also be an initial trigger for this
condition. (See "Clinical manifestations and diagnosis of localized, provoked vulvodynia (formerly
vulvar vestibulitis)".)

Postcoital vulvovaginal pruritus and pain Seminal plasma allergy or hypersensitivity is a rare
disorder characterized by postcoital vulvovaginal itching, burning, edema, and erythema with or
without systemic signs and symptoms. Vaginal discharge is not a typical feature. Complaints occur
immediately or within one hour after contact with seminal plasma. Most affected women are under
age 40 years and have a family history of atopy.
The diagnosis is based on absence of symptoms with condom use and on positive skin testing with
a pooled sample of seminal fluid. (See "Allergic reactions to seminal plasma".)
Desquamative inflammatory vaginitis Desquamative inflammatory vaginitis is a rare, chronic
clinical syndrome of unknown etiology that usually occurs in perimenopausal women. Patients
present with purulent vaginal discharge, vulvovaginal burning or irritation, dyspareunia, and vulvar
and vaginal erythema. (See"Desquamative inflammatory vaginitis".)
The diagnosis requires all of the following criteria:
At least one of the following symptoms: vaginal discharge, dyspareunia, pruritus, burning,
irritation
Vaginal inflammation (spotted ecchymotic rash, erythema, focal or linear erosion)
Vaginal pH >4.5
Saline microscopy showing increased parabasal and inflammatory cells (ie, leukocyte to
epithelial cell ratio greater than 1:1)
Persistent genital malodor The normal odor of vaginal secretions cannot be clearly defined, but
is probably slightly sour due to lactic acid and volatile sulfur compounds. Persistent genital malodor
can seriously impair a womans quality of life; the cause is difficult to identify after readily
diagnosable causes have been excluded. These causes include [21]:
Neglected foreign body (including retained tampon)
Bacterial vaginosis
Trichomoniasis
Infectious ulcer/pelvic inflammatory disease (PID)
Pelvic fistula (rectovaginal, vesicovaginal, ureterovaginal)
Hidradenitis suppurativa
Chronic constipation
Urinary incontinence

Fecal incontinence
Poor hygiene
Malignant ulcer
Excessive genital perspiration and local bacterial colonization related to obesity
Other potential causes of malodor include metabolic disorders (see "Inborn errors of metabolism:
Epidemiology, pathogenesis, and clinical features", section on 'Abnormal odors'), olfactory reference
syndrome [22], and olfactory hallucinations (see "Nonepileptic paroxysmal disorders in adolescents
and adults", section on 'Olfactory hallucinations').
Management depends on determining a cause. In the absence of poor hygiene, frequent washing
and vaginal douching are not helpful and can be harmful. Excessive soaping of the genital area can
cause a chemical vulvitis and douching (rinsing of the vagina with vinegar or an antiseptic with the
aid of a douche bag) can increase the risk of vaginal and pelvic infection [23,24].
For women with an elevated vaginal pH or lack of lactobacilli on Gram stain of vaginal discharge, a
trial of antibiotics for anaerobic infection is reasonable (eg,metronidazole 500 mg orally twice daily
for seven days). For women with no identifiable abnormalities, use of a specific medical grade
stainless steel douching device (Water Works Douching Device) can be helpful. A randomized trial
including 140 women with perceived vaginal odor and no vaginal infection reported significant
improvement after douching daily for four weeks with tap water using this device [25]. In the Water
Works group, odor intensity scores fell from 7.3 to 1.8 (p<.001), which was superior to that among
women who used a conventional over-the-counter plastic douche bag, 7.2 to 3.4 (p<.003).
Other The following diagnoses are listed because clinicians sometimes attempt to diagnose and
treat women for these conditions. We do not believe they are causes of vaginitis.
Group B streptococcus Group B streptococcus (GBS) commonly colonizes the vagina:
approximately 20 percent of women are colonized with GBS [18,26]. Whether GBS is a pathogen in
vulvovaginitis is controversial. Some clinicians believe it has a pathogenic role in vulvovaginitis and
report an ameliorative effect on vulvovaginal symptoms with antibiotic treatment (oral penicillin
or clindamycin cream). We and most experts do not believe this organism has a pathogenic role in
symptomatic vulvovaginitis and that positive culture results merely reflect colonization, which is
facilitated by disruption of the normal vaginal bacterial environment [26]. Therefore, in women with
vaginitis, both GBS culture and treatment of positive culture results should be avoided.
"Non-specific bacterial vaginitis" The concept of non-specific bacterial vaginitis is no longer
acceptable. In the past, many women with bacterial vaginosis were given the diagnosis of nonspecific vaginitis, but this should no longer occur since clear diagnostic criteria for bacterial
vaginosis are now available. (See "Bacterial vaginosis", section on 'Diagnosis'.)
As discussed above, vaginal bacterial cultures are rarely indicated in women with vaginal discharge
and are frequently misleading, leading to unnecessary antibacterial therapy. Apart from Group A

streptococcus, a clear causal relationship between any bacteria and vaginitis has not been
established.
Treatment of infectious causes of vulvovaginitis should be targeted to the causative
organism. Sulfanilamide cream (eg, triple sulfa or AVC cream) has no role in the treatment of
vulvovaginitis, as it is less effective than other therapies (eg, metronidazole for trichomonas
vaginalis and bacterial vaginosis, fluconazole for candida vulvovaginitis) [27,28].
POSTDIAGNOSTIC MANAGEMENT Women with a confirmed diagnosis are treated, as
appropriate. (See individual topic reviews).
Patients with sexually transmitted infections may have an infected partner and are at increased risk
of acquiring other sexually transmitted diseases. Thus, sexual partners should be referred for
specific testing and treatment; partner delivered patient medication (PDPM) is an alternative.
Patients who continue to exhibit symptomsand/or have positive tests for sexually transmitted
infections after treatment are likely to have been reinfected by their sexual partner [7].
(See "Screening for sexually transmitted infections".)
MANAGEMENT OF PHYSIOLOGICAL LEUKORRHEA After exclusion of pathological causes
of vaginal discharge, women with a change in their normal vaginal discharge can be reassured that
changes in the volume and character of vaginal discharge are normal and can be due to changes in
diet, sexual activity, medication, stress, etc. Although hormonal therapy, such as
depot medroxyprogesterone acetate injection every three months or norethindrone acetate 5 mg
orally daily, will decrease estrogen levels and thus may decrease physiological leukorrhea, the use
of hormonal therapy for this indication alone is rarely appropriate given the side effects and risks
associated with these drugs.
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 10 th 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.)
Basics topics (see "Patient information: Vaginal discharge in adults (The
Basics)" and "Patient information: Vulvar itching (The Basics)")
Beyond the Basics topics (see "Patient information: Vaginal discharge in adult women
(Beyond the Basics)" and "Patient information: Vaginal yeast infection (Beyond the
Basics)" and "Patient information: Bacterial vaginosis (Beyond the Basics)" and "Patient

information: Gonorrhea (Beyond the Basics)" and "Patient information: Chlamydia (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
Vaginitis is the general term for disorders of the vagina caused by infection, inflammation, or
changes in the normal vaginal flora. Signs and symptoms are similar, irrespective of the
underlying etiology. (See 'Introduction' above and 'Causes of vaginitis' above.)
Women with vaginitis typically present with one or more of the following: change in vaginal
discharge, pruritus, burning, irritation, erythema, dyspareunia, spotting, and dysuria.
(See 'Patient presentation' above.)
Diagnostic evaluation for bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis is
important since these disorders account for over 90 percent of vaginitis in premenopausal
women. (See 'Causes of vaginitis' above and 'General principles' above.)
Clinical findings may suggest a particular diagnosis (table 1 and table 2). Measurement of
vaginal pH is the single most important finding that drives the diagnostic process and should
always be determined. Laboratory documentation of the etiology of vaginitis is mandatory
before initiating therapy, given the nonspecific nature of the symptoms. Empiric therapy should
be avoided because of frequent misdiagnosis and inappropriate therapy when assessment is
based on history and physical examination alone. (See 'Diagnostic evaluation' above.)
Trichomonas is classically associated with a greenish-yellow purulent discharge; candidiasis
with a thick, white, adherent, "cottage cheese-like" discharge; and bacterial vaginosis with a
thin, homogeneous, "fishy smelling" gray discharge. However, the appearance of the
discharge is not a reliable basis for diagnosis. (See'Physical examination' above.)
Saline microscopy should be performed to look for candidal buds or hyphae (picture 4),
motile trichomonads (picture 5), epithelial cells studded with adherent coccobacilli (clue cells
suggesting bacterial vaginosis (picture 7)), and polymorphonuclear cells.
(See 'Microscopy' above.)
Initial office evaluation (history and physical examination, vaginal pH, wet mount microscopy,
whiff test) correctly diagnoses 60 percent of Candida vulvovaginitis, 70 percent of
trichomoniasis, and 90 percent of bacterial vaginosis. (See 'Diagnostic evaluation' above.)
We suggest culture for Candida species or Trichomonas vaginalis (or a rapid antigen and
nucleic acid amplification test), as indicated by clinical findings, if microscopy is negative
because microscopy is not sufficiently sensitive to exclude these diagnoses in symptomatic
patients. Bacterial cultures are rarely indicated in women with vaginal discharge. (See 'Vaginal
culture' above.)
If the woman had minimal symptoms at the time of initial evaluation and the evaluation was
nondiagnostic, the evaluation should be repeated at a second visit when she is symptomatic.

In other cases, less common and rare infectious and inflammatory disorders need to be
considered. (See 'Women without a diagnosis after the initial evaluation' above.)

Tricomoniasis

INTRODUCTION Trichomoniasis is caused by the protozoan Trichomonas vaginalis. It is the

most common non-viral sexually transmitted disease (STD) worldwide. Women are affected more
often than men. Trichomoniasis is one of the three major causes of vaginal complaints among
reproductive aged women, along with bacterial vaginosis and candida vulvovaginitis [1], and a
cause of urethritis in men; however, the infection is often asymptomatic.
MICROBIOLOGY AND TRANSMISSION The organism responsible for trichomoniasis is the
flagellated protozoan Trichomonas vaginalis, which principally infects the squamous epithelium in
the urogenital tract: vagina, urethra, and paraurethral glands. Other less common sites include the
cervix, bladder, Bartholin glands, and prostate. Humans are the only natural host.
Trichomoniasis is virtually always sexually transmitted. Although survival on fomites has been
reported, fomites have no proven role in transmission. Women can acquire the disease from other
women, but men do not usually transmit the infection to other men.
The incubation period is unknown; however, in vitro studies suggest an incubation period of 4 to 28
days in about 50 percent of patients [2].

Coexistence of T. vaginalis and bacterial vaginosis pathogens is common, with coinfection rates of
60 to 80 percent [3].
PREVALENCE Trichomonal infection does not need to be reported to public health authorities,
so prevalence is difficult to determine. Prevalence estimates vary according to the population
studied and method used for diagnosis.
The best estimate of the prevalence of trichomoniasis in reproductive aged women in the United
States was provided by the National Health and Nutrition Examination Survey (NHANES), in which
a nationally representative sample of 3754 women aged 14 to 49 years self-collected vaginal swab
specimens that were subsequently evaluated for T. vaginalis by polymerase chain reaction (PCR)
[4]. The overall prevalence of T. vaginalis was 3.1 percent, and increased with age. Prevalence was
highest in non-Hispanic black women (13.3 percent) and lowest in non-Hispanic white women (1.3
percent).
The overall prevalence of T. vaginalis was higher (8.7 percent) in a study of women tested by a
nucleic acid amplification test in clinical settings, and varied from 5 to 7 percent in family planning,
internal medicine/family practice, and obstetric and gynecology offices to 16 percent in prisons and
sexually transmitted disease (STD) clinics [5]. In contrast to the NHANES, these women were
tested because of symptoms or the presence of risk factors for chlamydia or gonorrhea. Lastly, a
study in 15 STD clinics participating in the STD Surveillance Network (SSuN) reported the
prevalence of T. vaginalis was 26 percent among 17,952 symptomatic women tested, 6.5 percent
among 3909 asymptomatic women screened, and 29 percent among 92 HIV-infected
women tested/screened [6].
T. vaginalis can be identified in 70 percent of the male sexual partners of infected women [7],
although carriage in men is often self-limited (see 'Sex partners' below). A study using an
educational internet program to offer sexually active men free nucleic acid amplification tests for T.
vaginalis on self-collected specimens reported an overall prevalence of 3.7 percent among the 1699
men, and the highest prevalence by age group was in men aged 40 to 49 years (5.2 percent) [8].
CLINICAL FEATURES
Women In women, trichomoniasis ranges from an asymptomatic carrier state to an acute,
severe inflammatory disease. As many as 50 percent of infected women are asymptomatic,
although many of these women eventually become symptomatic. Asymptomatic carriage can persist
for prolonged periods of time (at least three months), thus it is often not possible to ascertain when
or from whom the infection was acquired [9,10].
Vaginitis Common signs and symptoms of acute infection include a purulent, malodorous, thin
discharge associated with burning, pruritus, dysuria, frequency, lower abdominal pain, or
dyspareunia. Symptoms may be worse during menstruation [11]. Postcoital bleeding can occur.
Physical examination often reveals erythema of the vulva and vaginal mucosa. The classically
described green-yellow, frothy, malodorous discharge occurs in 10 to 30 percent of symptomatic
women. Punctate hemorrhages may be visible on the vagina and cervix ("strawberry cervix" in 2
percent of cases).
In chronic infection, signs and symptoms are milder and may include pruritus and dyspareunia, with
scanty vaginal secretion.

Men In men, T. vaginalis infection is asymptomatic in over three-quarters of cases and often
transient (spontaneous resolution within 10 days) [7,12]. However, untreated infection can persist
for months [13]. Symptoms, when present, are the same as those for urethritis from any cause and
consist of a clear or mucopurulent urethral discharge and/or dysuria. They may also have mild
pruritus or burning sensation in the penis after sexual intercourse. (See "Urethritis in adult men",
section on 'Clinical manifestations'.)
CONSEQUENCES
Women Untreated trichomonal vaginitis may progress to urethritis or cystitis. In addition, T.
vaginalis has been associated with a range of adverse reproductive health outcomes, including
cervical neoplasia [14,15], posthysterectomy cuff cellulitis or abscess [16], atypical pelvic
inflammatory disease in women infected with human immunodeficiency virus (HIV) [17], and
infertility [18]. It may also increase women's susceptibility to HIV-1 infection by up to two-fold [1921].
Pregnancy In a 2014 systematic review and meta-analysis of the association between T.
vaginalis and perinatal outcomes, the risk of preterm birth was increased by 42 percent among
infected women (RR 1.42, 95% CI 1.15-1.75; 9 studies) [22]. The risks of premature rupture of
membranes and delivery of a small for gestational age infant were similarly increased, but each of
these findings was based on only two studies. Whether treatment in pregnancy affects these risks,
positively or negatively, is unclear. (See 'Pregnant women' below.)
Infants born to infected mothers may contract infection during delivery. Signs and symptoms in
neonates may include fever, respiratory problems, urinary tract infection, nasal discharge, and, in
girls, vaginal discharge [23-26]. Treatment of asymptomatic infants is not necessary as
spontaneous resolution will occur when estrogen levels wane to normal prepubescent levels [12].
(See "Vulvovaginal complaints in the prepubertal child".)
Men T. Vaginalis in men has been associated with prostatitis, balanoposthitis, epididymitis,
infertility, and prostate cancer. (See "Approach to dysuria in the adult man" and "Risk factors for
prostate cancer", section on 'Trichomonas vaginalis infection'.)
DIAGNOSIS
Women The diagnosis of trichomonas is based on laboratory testing (motile trichomonads on
wet mount, positive culture, positive nucleic acid amplification test, or positive rapid antigen or
nucleic acid probe test). As with other types of vaginitis, none of the clinical features of
trichomoniasis is sufficiently sensitive or specific to allow a diagnosis based upon signs and
symptoms alone (table 1) [27-29]. In one study, if the classic clinical features of trichomoniasis in
women were used alone for diagnosis, 88 percent of infected women would not be diagnosed and
29 percent of uninfected women would be falsely diagnosed as infected [30].
The general diagnostic approach to women with vaginal discharge is reviewed separately.
(See "Approach to women with symptoms of vaginitis".)
Microscopy and pH The presence of motile trichomonads on wet mount is diagnostic of
infection, but they are identified in only 60 to 70 percent of culture-confirmed cases (picture 1) [29].
The motion is jerky and spinning (movie 1 and movie 2); organisms remain motile for 10 to 20
minutes after collection of the sample. Other findings that are almost invariably present with

trichomonas infection, but nondiagnostic, include an elevated vaginal pH (>4.5) and an increase in
polymorphonuclear leukocytes on saline microscopy.
Fixation and staining is not useful because T. vaginalis may not have the typical pear-shaped
flagellated form; instead, it may resemble polymorphonuclear leukocytes or lose morphologic
characteristics during fixation and staining, making the etiologic identification difficult [31].
Culture Culture is useful in patients with elevated vaginal pH and increased numbers of
polymorphonuclear leukocytes but an absence of motile trichomonads and clue cells on wet mount,
or when microscopy is unavailable or yields unreliable results. The "InPouch" T. vaginalis culture
system has high sensitivity (over 80 percent), takes 3 days to obtain results, and is commercially
available [32,33]. Culture on Diamond's medium was previously the gold standard for diagnosis
because of high sensitivity (95 percent) and specificity (>95 percent). However, this test is not
widely available and takes up to seven days to obtain a result. Polymerase chain reaction (PCR)
detection has become the new gold standard for diagnosis of trichomoniasis.
Rapid antigen, DNA hybridization probe, and nucleic acid amplification tests Rapid
diagnostic kits can be useful in areas of high prevalence where microscopy or culture is not
available (eg, sexually transmitted disease [STD] clinics and inner city clinics serving the uninsured
are high prevalence sites). The following tests can be performed by the clinician at the point of care
and are commercially available.
AFFIRM VP III - The Affirm VP III Microbial Identification System (Becton Dickinson) test
uses a DNA hybridization probe on a vaginal swab specimen. Results are available in 45
minutes. Although sensitivity and specificity have been reported to exceed 95 percent, in sideby-side testing, this method was inferior to target capture and transcription mediated
amplification (sensitivity 63.4 versus 100 percent [34]).
OSOM Trichomonas Rapid Test - The OSOM Trichomonas Rapid Test (Genzyme) is a
rapid antigen test that uses an immunochromatographic technology on a vaginal swab
specimen. Results are available in 10 minutes. It has sensitivity of 88.3 percent (and in some
studies >94 percent) and specificity of 98.8 percent [35-37].
The following commercially available nucleic acid amplification test (NAAT) requires instrumentation
and is performed on specimens sent to the laboratory. The term NAAT generally refers to
polymerase chain reaction (PCR) or reverse transcriptase PCR [38]. As discussed above, PCR
detection is now accepted as the gold standard for diagnosis of trichomoniasis.
APTIMA Trichomonas vaginalis assay (Gen-Probe) The APTIMA Trichomonas vaginalis
assay uses target capture and transcription mediated nucleic acid amplification to detect
species specific ribonucleic acid (RNA), including N. gonorrhoeae, C. trachomatis and T.
vaginalis on a single vaginal swab or urine specimen [39]. Reported sensitivity ranges from 97
to 100 percent and specificity ranges from 87 to 100 percent [34,40-42]. The APTIMA TV
assay has demonstrated superior performance in side-by-side comparisons with other
diagnostic methods in all patient populations and specimen types tested (vaginal discharge,
urine). Because the prevalence of Trichomonas is equal to or greater than chlamydia and
gonorrhea, there is an increasing trend toward screening for all three infections simultaneously
with NAAT [38].
Other tests:

Amplicor Amplicor (Roche) is a PCR assay for detection of N. gonorrhoeae and C.

trachomatis that has been modified to detect T. vaginalis invaginal/endocervical swabs or
urine; sensitivity and specificity are 88 to 97 percent and 98 to 99 percent, respectively [9]. It is
not commercially available, but has been cleared by the United States Food and Drug
Administration (FDA).
NuSwab VG - NuSwab VG is a nucleic acid amplification single specimen assay for the
detection of trichomoniasis, bacterial vaginosis, and vulvovaginal candidiasis that has also
been cleared by the FDA, but not yet commercially available.
The excellent performance characteristics of these tests are illustrated by the following comparative
studies, which compare performance of traditional and rapid testing methods:
One study recruited 330 sexually active adolescent females seeking care at a teen health
clinic or emergency department and tested them for T. vaginalis using the four test methods
discussed above: wet mount, culture (InPouch TV), rapid antigen testing (OSOM TV), and
transcription-mediated amplification testing (APTIMA TV) [43]. The sensitivities of the four
methods were 65, 96, 90, and 98 percent, respectively.
Another study enrolled 296 female and 298 male subjects seeking care at a STD clinic [39].
Specimens from each subject were tested for trichomoniasis using transcription-mediated
amplification (APTIMA TV), wet mount microscopy, culture, and PCR tests. The subject was
diagnosed with trichomoniasis if any of these tests were positive. In women, vaginal swab
APTIMA TV was more sensitive than wet mount or culture (96.6 versus 54.6 and 75.0 percent,
respectively). In men, urethral swab APTIMA TV was more sensitive than culture or PCR (95.2
versus 28.6 and 54.8 percent, respectively).
In a third study, specimens were retrieved consecutively from 766 patients with vaginal
complaints and/or with histories suggestive of a STD and tested by both the AFFIRM and the
APTIMA trichomonas vaginalis assays [34]. Overall, 5.1 percent of patients were positive for T
vaginalis (defined as a specimen with two positive test results for T vaginalis by two different
molecular assays). The APTIMA assay was statistically more sensitive than the AFFIRM assay
(100 versus 63.4 percent); specificity was similar (APTIMA 100 percent, AFFIRM 99.9
percent).
Cervical cytology Trichomonads are sometimes reported as an incidental finding on tests
performed for cervical cancer screening. Liquid-based cervical cytology is not a sensitive test for
diagnosis of trichomoniasis, but treatment of women with trichomonads noted on liquid-based
cervical cytology is reasonable since specificity is high. In a study that performed both liquid-based
cervical cytology and culture for T. vaginalis on 203 consecutive women, 28 had a liquid-based
smear positive for trichomonads and 44 had positive cultures [44]. Although sensitivity of liquidbased smears for trichomonas infection was low (61 percent), specificity was high (99 percent),
resulting in a false positive rate of only 1 percent.
Conventional Papanicolaou (Pap) smears do not perform as well for diagnosis of trichomoniasis.
Sensitivity is similar (51 to 63 percent) to liquid based tests, but false positive results are common (7
percent) [45]. This makes the positive predictive value poor in a low prevalence population. Thus,
the Pap smear should not be used to diagnose trichomoniasis. Asymptomatic women with
trichomonads identified on a conventional Pap smear should be evaluated by wet mount, or

culture,NAAT, or rapid test if the wet mount is negative, and treated only if the diagnosis is
confirmed.
Men The most reliable methods for diagnosis of trichomonas urethritis in the male are by culture
or a nucleic acid amplification test (ie, PCR or transcription-mediated amplification [TMA]) of first
fraction urine or a urethral swab specimen, but these tests are not widely available [39,46]. Saline
microscopy of a urethral swab specimen has low sensitivity and is not recommended.
(See "Urethritis in adult men".)
SCREENING In the United States, the Centers for Disease Control and Prevention (CDC)
recommend screening for T. vaginalis in women [47]:
with new or multiple partners
with a history of sexually transmitted diseases (STDs)
who trade sex for drugs or money
who use injection drugs
Issues related to screening for T. vaginalis are discussed separately. (See "Screening for sexually
transmitted infections", section on 'Trichomoniasis'.)
TREATMENT Treatment is indicated for both symptomatic and asymptomatic women and men.
Treatment reduces the prevalence of T. vaginalis carriage in the population, relieves symptoms, and
reduces the risk of sequelae (including acquisition/transmission of human immunodeficiency virus
[HIV]). The 5-nitroimidazole drugs (metronidazole or tinidazole) are the only class of drugs that
provide curative therapy of trichomoniasis. Patients should be instructed to avoid intercourse until
they and their partners have completed treatment and are asymptomatic, which generally takes
about a week. After single dose therapy or treatment of asymptomatic patients, the couple should
abstain from intercourse until both partners have waited at least seven days since taking the last
antibiotic dose. There are no studies on how long trichomonads remain viable after treatment is
initiated or completed.
Clinicians should also screen the patient for other STDs when she presents with trichomoniasis.
(See "Screening for sexually transmitted infections".)
Nonpregnant women Treatment is indicated in all nonpregnant women diagnosed with
trichomoniasis, even if asymptomatic. The rationale for treatment of asymptomatic women is that if
left untreated, they continue to transmit the infection to sexual partners and up to one-third of
symptomatic women become symptomatic within six months [11].
5-nitroimidazole drugs The 5-nitroimidazole drugs (metronidazole or tinidazole) are the only
class of drugs that provide curative therapy of trichomoniasis. Most strains of T. vaginalis are highly
susceptible to these agents [48]. Randomized trials using these drugs have generally reported cure
rates of 90 to 95 percent [49-51]. Therapy with drugs other than 5-nitroimidazoles is an option, but
cure rates are low (50 percent) [52,53].
We recommend treatment with a single 2 gram oral dose of either tinidazole or metronidazole (ie,
four 500 mg tablets) [40,51]. We believe cure rates with tinidazole are comparable to those of
metronidazole, but the drug is better tolerated. Although tinidazole was significantly more effective
than metronidazole in several randomized trials, most of these trials were subject to bias since
outcome was assessed by clinicians who were not blinded to the patient's treatment group [51].

An alternative multidose regimen is metronidazole 500 mg orally twice a day for seven days [40].
There is no United States Food and Drug Administration (FDA) approved multiple dose regimen
for tinidazole. Similar cure rates are obtained with single and multiple dose regimens (cure rate for
single dose: 82 to 88 percent; cure rate for multiple dose: 85 to 90 percent) [49,51,54]. The
advantages of single-dose therapy include better compliance, a shorter period of alcohol avoidance,
and possibly decreased Candida superinfection (although there is no evidence of decreased
Candida superinfection). However, side effects (eg, nausea, vomiting, headache, metallic taste,
dizziness) appear to be dose related and thus occur less frequently with the lower doses used in
multiple dose, prolonged therapy [51].
Oral is preferred to vaginal therapy since systemic administration achieves higher drug levels and
therapeutic drug levels in the urethra and periurethral glands, which serve as endogenous
reservoirs of organisms that can cause recurrence. Cure rates for vaginal therapy
with metronidazole gel are 50 percent, which is significantly lower than with oral therapy [40,51].
Patients should be advised to not consume alcohol for 24 hours after metronidazole treatment and
for 72 hours after tinidazole treatment because of the possibility of a disulfiram-like (Antabuse
effect) reaction [40].
Allergy to 5-nitroimidazole drugs Given the low efficacy of any drug other than the 5nitroimidazole drugs (see '5-nitroimidazole drugs' above), we suggest patients with allergies
to metronidazole or tinidazole be referred for desensitization rather than using an alternative class
of drugs. Desensitization is very effective: in one series, all 15 women who underwent
desensitization subsequently eradicated their infections [55].
Follow-up Follow-up is unnecessary for women who become asymptomatic after treatment or
who were initially asymptomatic, given the high efficacy of 5-nitroimidazole drugs.
Sex partners Treatment of sex partners is indicated because maximal cure rates in infected
women are achieved when their sexual partners are treated simultaneously [56]. It is not mandatory
to identify the organism in a male partner before treating him (ie, Expedited Partner Therapy [EPT]),
given the high rate of concurrent carriage (30 to 70 percent [7]), difficulty of diagnosis in males,
lower compliance when the partner is asked to visit his health care provider, and the convenience,
low morbidity, and low cost of empiric treatment.
Treatment of sex partners is identical to that for nonpregnant females, with preference for a single
dose regimen to maximize compliance (ie, single oral dose of eithertinidazole or metronidazole 2
grams). Neither partner should resume intercourse until both partners have completed treatment,
otherwise reinfection can occur.
Ideally, if possible, sexual partners should be referred for diagnostic evaluation because concurrent
sexually transmitted infections, such as chlamydia and gonorrhea, are common and should be
diagnosed and treated, if present [57,58]. However, if the one partner has been diagnosed with
chlamydia or gonorrhea, EPT is also an option for these infections [57].
Men with urethritis Treatment of men with urethritis is discussed separately. (See "Urethritis in
adult men".)
Pregnant women

Symptomatic pregnant women Metronidazole is the drug of choice for treatment of

symptomatic trichomoniasis in pregnancy. Some clinicians avoid its use in the first trimester
because it crosses the placenta, thus there is a potential for teratogenicity. The drug is mutagenic in
bacteria and carcinogenic in mice; however, these effects have never been observed in humans. A
1997 meta-analysis did not find any relationship between metronidazole exposure during the first
trimester of pregnancy and congenital malformations [59]. Based on this and subsequent reports,
the Centers for Disease Control and Prevention (CDC) no longer discourage the use of
metronidazole in the first trimester [47].
In pregnant women, some clinicians prefer metronidazole 500 mg twice daily for five to seven days
to the 2 gram single dose regimen [60] because of the lower frequency of side effects in women
who already have a high prevalence of nausea, but both regimens are acceptable.
An alternative approach is clotrimazole 1% cream inserted vaginally (preferably at bedtime) for
seven consecutive days. This often results in symptomatic relief, but not eradication of the
organisms.
There is sparse information on the safety of tinidazole in pregnancy; therefore, we avoid its use,
especially in the first trimester.
Asymptomatic pregnant women We suggest not treating asymptomatic infections during
pregnancy because randomized trials have found that it does not prevent, and in some trials even
increased, the risk of preterm delivery [61,62]. For example, one trial randomly assigned 617
women with culture proven asymptomatic infection at 16 to 23 weeks of gestation to receive either
two 2 gram doses of metronidazole or placebo 48 hours apart [61]. All women were retreated with
the same regimen at 24 to 29 weeks of gestation. The major findings from this trial were:
T. vaginalis infection resolved in 93 percent of metronidazole-treated women and 35 percent
of the placebo group.
The rate of preterm birth was significantly higher in treated than in control women (19 versus
11 percent, RR 1.8; 95% CI 1.2-2.7), primarily related to an increased frequency of
spontaneous preterm labor (10.2 versus 3.5 percent, RR 3.0; 95% CI 1.5-5.9).
The increased risk of preterm delivery was unexpected, and discordant with some observational
data [63]. The authors and others [64] have speculated that use of twice the standard single 2
gram metronidazole dose might have disturbed colonization of normal vaginal flora, thus enhancing
the potential for infection-related preterm labor. Since more extensive culturing was not performed,
the presence of other infections was not determined. (See "Pathogenesis of spontaneous preterm
birth", section on 'Bacteria'.)
At term, however, asymptomatic women may opt to undergo treatment to prevent perinatal
transmission [40].
Sex partners Treatment of sexual partners is indicated. In cases where an asymptomatic
pregnant woman is not treated, reinfection of the treated partner can be minimized by avoidance of
sexual intercourse or use of condoms.
Breastfeeding women 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 [65].

Outcomes data of maternal metronidazole use did not show a significant increase in adverse events
compared to use of other antimicrobials, although a cohort study found a nonsignificant trend
toward more loose stools and more candidal colonization in metronidazole-exposed infants.
Since the relative infant dose of metronidazole is high (29 percent) with maternal administration of
the 2 gram one-time dose, a cautious approach for mothers receiving this dose is to express and
discard their milk for 12 to 24 hours to allow excretion of the drug [66].
In mothers using tinidazole, which has a longer half-life than metronidazole, the CDC suggests
interrupting breastfeeding for three days after the last dose [40].
HIV-positive women Studies of the impact of T. vaginalis infection on genital HIV shedding have
reported strong evidence that trichomoniasis in HIV-infected individuals increases the risk of HIV
transmission to uninfected partners, as well as acquisition by women [67-69]. There is some
evidence that treatment of trichomoniasis reduces HIV shedding [67,68,70].
Standard treatment recommendations for trichomoniasis have been based on studies conducted in
HIV-negative persons, but there is increasing evidence that HIV-positive women should receive
longer treatment, particularly if they are receiving antiretroviral therapy. In a trial where 270 HIVpositive women with culture confirmed T. vaginalis were randomly assigned to treatment
with metronidazole 2 gram single dose or metronidazole 500 mg twice per day for seven days,
single dose therapy was less effective than multiple-day therapy [71]. The seven-day treatment
group had a lower rate of positive cultures 6 to 12 days after treatment completion (8.5
percent[11/130 women] versus 16.8 percent [21/125 women]; RR 0.5, 95% CI 0.25-1.00) and at 3
months (11 percent [8/73 women] versus 24.1 percent [19/79 women]; RR 0.46, 95% CI 0.21-0.98).
Of note, all women were given a 2 gram metronidazole dose to deliver to their sex partners. In
another trial, HIV-infected women on antiretroviral therapy had 2.6-fold greater risk of persistent
trichomoniasis than HIV-infected women not on antiretroviral therapy, but this risk could be
minimized by multiday dosing [72].
There is a high prevalence of bacterial vaginosis in HIV-positive/T. vaginalis positive women and an
association between the presence of bacterial vaginosis and early failure of single
dose metronidazole treatment of trichomoniasis has been observed [73].
Based on these data, we treat HIV-positive women with T. vaginalis with metronidazole 500 mg
twice per day for seven days. We do not use single dose metronidazole for treatment of these
women, given the high prevalence of asymptomatic bacterial vaginosis co-infection and other
factors that may render metronidazole less effective in this population.
The CDC also suggests rescreening HIV-positive women three months after completion of therapy
based on the high proportion of recurrent or persistent T. vaginalis infection in this population and
the association between HIV and this infection.
Refractory cases The most common causes of treatment failure are noncompliance and
reinfection. Compliance is enhanced with single dose therapy. Reinfection is unlikely if the partner
was treated concurrently or sexual intercourse was avoided until both partners completed
treatment.
The CDC recommendation for therapy of recurrent trichomoniasis after failure of a single dose
of metronidazole 2 grams is to give metronidazole 500 mg twice daily for seven days (total dose 7

grams) [40]. If this regimen fails, tinidazole or metronidazole is administered at a dose of 2 grams
per day for five days (total dose 10 grams). These regimens can be effective in patients with low
levels of metronidazole resistance, which was noted in 4 percent of T. vaginalis isolates of women
attending STD clinics in six cities in the United States [74].
If this fails, the CDC recommends in vitro culture and drug susceptibility testing (available from the
CDC Division of STD Prevention, telephone 404-718-4141) and referral to a specialist. Therapeutic
options include maximum tolerated doses of metronidazole, or preferably tinidazole (2 to 4 grams
daily in divided doses) for 14 days. Considerable success with tinidazole in refractory disease has
been reported, although the optimal dose has not been established [75,76]. Cross resistance to
tinidazole is frequent, but not inevitable [77,78]. Patients with high level metronidazole resistance
are usually successfully treated by prolonged and high dose tinidazole therapy. High dose tinidazole
has a better safety profile and is better tolerated than high dose metronidazole.
Case reports have described successful use of nimorazole, ornidazole, niridazole, furazolidone, and
hamycin [12], whereas a trial of nitazoxanide in three women with difficult to eradicate T. vaginalis
reported lack of efficacy [79].
Rare patients who do not have a response to nitroimidazoles have been treated with
topical paromomycin (250 mg daily for two weeks) [80]. Paromomycin is not available commercially
in the United States as a cream and has to be made by a compounding pharmacy. Little is known
about this preparation, but severe local side effects (pain, mucosal ulceration) can occur [81]. We
recommend not using it.
PREVENTION The risk of acquiring T. vaginalis infection can be reduced by consistent use of
condoms and limiting the number of sexual partners. Spermicidal agents such as nonoxynol-9
reduce the rate of transmission [82].
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 10 th 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.)
Basics topic (see "Patient information: Trichomoniasis (The Basics)")
SUMMARY AND RECOMMENDATIONS
Trichomoniasis is caused by the protozoa Trichomonas vaginalis. It is virtually always
sexually transmitted and can be identified in 70 percent of the male sexual partners of infected
women. Coinfection with other sexually transmitted diseases (STDs) and bacterial vaginosis is
common. (See 'Microbiology and transmission'above and 'Prevalence' above.)

Untreated trichomonal vaginitis may progress to urethritis or cystitis. T. vaginalis has been
associated with a range of adverse reproductive health outcomes, including cervical
neoplasia, posthysterectomy cuff cellulitis or abscess, atypical pelvic inflammatory disease in
women infected with human immunodeficiency virus (HIV), infertility, and preterm birth. It may
also increase women's susceptibility to HIV-1 infection. (See 'Consequences' above.)
Clinical manifestations in women range from an asymptomatic carrier state to an acute,
severe inflammatory disease. Signs and symptoms include a purulent, malodorous, thin
discharge with associated burning, pruritus, dysuria, frequency, and dyspareunia. Men are
often asymptomatic, but have developed urethritis. (See'Clinical features' above.)
Asymptomatic carriage can occur for prolonged periods of time, thus it is not necessarily
possible to ascertain when or from whom the infection was acquired. (See'Clinical
features' above.)
The diagnosis of trichomonas is based on laboratory testing (motile trichomonads on wet
mount (picture 1), positive culture, positive NAAT, or positive rapid antigen or nucleic acid
probe test). None of the clinical features of trichomoniasis is sufficiently sensitive or specific to
allow a diagnosis based upon signs and symptoms alone. We suggest culture (if available) in
patients with suggestive clinical findings (eg, elevated vaginal pH, increased numbers of
polymorphonuclear leukocytes but an absence of motile trichomonads and clue cells on wet
mount) or when microscopy is unavailable or unreliable. (See 'Diagnosis' above.)
If culture for trichomoniasis is not available, rapid antigen tests, DNA hybridization probe, and
nucleic acid amplification tests for diagnosis of Trichomonas vaginalis are commercially
available and can be used as an alternative to culture. Nucleic acid amplification tests are the
most accurate. (See 'Rapid antigen, DNA hybridization probe, and nucleic acid amplification
tests' above.)
Treatment is indicated for both symptomatic and asymptomatic women and men. Treatment
reduces the prevalence of T. vaginalis carriage in the population, relieves symptoms, and
reduces the risk of sequelae (including acquisition/transmission of HIV). For nonpregnant
women and their sex partners, we recommend a single oral dose of 2 grams of a 5nitroimidazole drug (eg, metronidazole, tinidazole) (Grade 1A). Single dose therapy is more
convenient and is as effective as multiple dose therapy. Oral administration is more effective
than topical administration. (See 'Nonpregnant women' above.)
Patients should be screened for other sexually transmitted infections. (See "Screening for
sexually transmitted infections".)
We suggest referral of sexual partners of infected women for evaluation of trichomoniasis
and concurrent sexually transmitted infections rather than Expedited Partner Therapy (EPT)
(Grade 2B). However, EPT is reasonable if compliance is an issue. (See 'Sex
partners' above.)
Symptomatic pregnant women should be treated. Metronidazole 500 mg twice daily for five
to seven days may be associated with less nausea than a single dose of 2 grams
metronidazole, but either regimen is acceptable. (See 'Symptomatic pregnant women' above.)
We suggest not treating asymptomatic trichomoniasis in pregnant women given the
potentially increased risk of preterm birth associated with antibiotic therapy (Grade 2B).
(See 'Pregnant women' above.)
For HIV-positive women with T. vaginalis, we suggest metronidazole 500 mg twice per day
for seven days rather than single dose therapy (Grade 2B). (See 'HIV-positive women' above.)

For patients with refractory trichomoniasis, we suggest increasing the dose and duration of
medication (Grade 2C). (See 'Refractory cases' above.)
Patients should be instructed to avoid intercourse until they and their partners have
completed treatment and are asymptomatic, which generally takes about a week.
(See 'Treatment' above.)

INTRODUCTION Bacterial vaginosis (BV) is the most common cause of vaginal discharge in
women of childbearing age, accounting for 40 to 50 percent of cases [1-3]. In the United States, the
National Health and Nutrition Examination Survey (NHANES), which included results from selfcollected vaginal swabs from over 3700 women, estimated the prevalence of BV was 29 percent in
the general population of women aged 14 to 49 years and 50 percent in African-American women
[4]. This included both symptomatic and asymptomatic infection. Worldwide, BV is common among
women of reproductive age, with variations according to the population studied [5].
The absence of inflammation is the basis for the term "vaginosis" rather than "vaginitis."
PATHOGENESIS AND MICROBIOLOGY Bacterial vaginosis (BV) represents a complex change
in the vaginal flora characterized by a reduction in concentration of the normally dominant
hydrogen-peroxide producing lactobacilli and an increase in concentration of other organisms,
especially anaerobic gram negative rods [6-9]. The major bacteria detected are Gardnerella
vaginalis, Prevotella species, Porphyromonas species, Bacteroides species, Peptostreptococcus sp
ecies, Mycoplasma hominis,Ureaplasma urealyticum, and Mobiluncus species
[6]. Fusobacterium species and Atopobium vaginae are also common. The mechanism by which the
floral imbalance occurs and the role of sexual activity in the pathogenesis of BV are not clear, but
formation of an epithelial biofilm containing G. vaginalis appears to play an important role [10-13].
Hydrogen-peroxide producing lactobacilli appear to be important in preventing overgrowth of the
anaerobes normally present in the vaginal flora. With the loss of lactobacilli, pH rises and massive
overgrowth of vaginal anaerobes occurs. These anaerobes produce large amounts of proteolytic
carboxylase enzymes, which break down vaginal peptides into a variety of amines that are volatile,
malodorous, and associated with increased vaginal transudation and squamous epithelial cell
exfoliation, resulting in the typical clinical features observed in patients with BV (see 'Clinical
features' below). The rise in pH also facilitates adherence of G. vaginalis to the exfoliating epithelial
cells.
The difference in vaginal flora between women with and without BV was illustrated in a study that
used broad range DNA probes to determine the vaginal flora of 27 women with BV and 46 controls
[14]. Overall, 35 bacterial phylotypes were identified in women with BV, including 16 which were
newly recognized. Women with BV had a mean of 12.6 phylotypes (range 9 to 17) per sample
compared to 3.3 phylotypes (range 1 to 6) per sample in women without BV. The organisms newly
identified by polymerase chain reaction (PCR) include fastidious bacteria termed "BV associated
bacterium (BVAB) 1, 2 and 3" in the Clostridiales order, which appear to be specific indicators of BV
[15].

However, increasing evidence suggests that G. vaginalis is the key player in the pathogenesis of BV
and the development of a biofilm may be an essential component of this process, in addition to the
gradual overgrowth of resident anaerobic vaginal flora [16]. In this model, a cohesive form of G.
vaginalis adheres to the vaginal epithelium and then becomes the scaffolding to which other
species adhere [17]. This hypothesis is supported by a study of microbiota on the epithelial surfaces
of vaginal biopsy specimens from women with BV that showed a biofilm adhered to part or all of the
epithelium, and G. vaginalis comprised 90 percent of bacteria in the biofilm, while Atopobium
vaginae accounted for most of the remainder [10]. Subsequent desquamation of these epithelial
cells would result in the classic clue cells diagnostic of the disorder (see 'Diagnosis' below). In
contrast, most healthy controls had unstructured accumulations of bacteria within secretions loosely
attached to epithelial surfaces.
Extracellular DNA (eDNA) is a factor in the structural stability of biofilms in a variety of bacterial
species and appears to play an important role in the establishment and maintenance of the G.
vaginalis biofilm in BV [18]. The presence of a biofilm may make it difficult to eradicate BV and
increase the rate of recurrence, but discovery of the role of eDNA has led to the hypothesis that a
DNase might be able to destroy the eDNA that helps to maintain the BV biofilm.
RISK FACTORS Sexual activity is a risk factor for bacterial vaginosis (BV), and most experts
believe that BV does not occur in women who have never had vaginal intercourse [19,20].
Epidemiologic studies are strongly supportive of sexual transmission of BV pathogens. In a
systematic review and meta-analysis of 43 observational studies, sexual contact with new and
multiple male and female partners was associated with an increased risk of BV, while condom use
was associated with a decreased risk [21].
BV is highly prevalent (25 to 50 percent) in women who have sex with women (WSW), and is
associated with increasing numbers of female sexual partners, a female partner with symptomatic
BV, and various sexual practices, suggesting sexual transmission is an important factor [22-26].
However, in one study, sexually active monogamous WSW partnerships over six months tended to
have concordant, stable, vaginal microbiota, which was most concordant for normal flora [24]. This
suggests that longer duration, sexually active partnerships led to stability and alignment of a
favorable vaginal microbiota in WSW couples.
Further, the presence of other sexually transmitted infections appears to be associated with an
increased prevalence of BV. In a systematic review and meta-analysis of studies evaluating the
association between BV infection and herpes simplex virus (HSV)-2 infection, women infected with
HSV-2 had a 55 percent higher risk of BV infection compared with women who were HSV-2
uninfected [27]. Similarly, a five-year prospective cohort study reported that BV was both more
prevalent and more persistent among HIV-infected women compared with those without HIV [28].
Conversely, bacterial vaginosis may also be a risk factor for HIV acquisition [29]. (See"HIV and
women", section on 'Bacterial vaginosis, genital ulcers, and pelvic inflammatory disease'.)
In addition to sexual and infectious risk factors, most studies indicate douching and cigarette
smoking are risk factors for acquisition of BV among sexually active women [1,2,24,30-35].
Although some degree of genetic susceptibility to BV is likely, no association between a gene
polymorphism and BV has been established [36].
Use of condoms and estrogen-containing contraceptives may be protective factors [37].

CLINICAL FEATURES Fifty to 75 percent of women with bacterial vaginosis (BV) are
asymptomatic [19,38,39]. Symptomatic women typically present with vaginal
discharge and/or vaginal odor [19,38,39]. The discharge is off-white, thin, and homogeneous; the
odor is an unpleasant "fishy smell" that may be more noticeable after sexual intercourse and during
menses [40].
BV alone does not cause dysuria, dyspareunia, pruritus, burning, or vaginal inflammation
(erythema, edema) [38,39]. The presence of these symptoms suggests mixed vaginitis (symptoms
due to two pathogens) [41].
Although BV does not involve the cervix, the disorder may be associated with acute cervicitis
(endocervical mucopurulent discharge or easily induced cervical bleeding) [42]. (See "Acute
cervicitis".)
DIAGNOSIS The general diagnostic approach to women with vaginal discharge is reviewed
separately. (See "Approach to women with symptoms of vaginitis".)
In clinical practice, the diagnosis of bacterial vaginosis (BV) in premenopausal women is usually
based on the presence of at least three Amsel criteria (characteristic vaginal discharge, elevated
pH, clue cells, fishy odor) if microscopy is available [43,44]. Use of Nugent or Hay/Ison criteria to
evaluate a Gram-stained smear of vaginal discharge is the diagnostic standard in research studies,
but requires more time, resources, and expertise [44]. If microscopy is not available, the diagnosis
should be based on findings on clinical examination (characteristic vaginal discharge, elevated
vaginal pH, fishy odor). Commercial tests that have acceptable performance compared with gram
stain include a DNA probe-based test for high concentrations of G. vaginalis (Affirm VP III) and
vaginal fluid sialidase activity test (OSOM BV Blue test). Use of the proline-aminopeptidase test
card (Pip Activity TestCard) is no longer recommended because of low sensitivity and specificity.
Amsel criteria The diagnosis of BV is usually based on Amsel criteria, which are simple and
useful in an office practice where microscopy is available [38]. The first three findings are
sometimes also present in patients with trichomoniasis (table 1).
Amsel criteria for diagnosis of BV (at least three criteria must be present):
Homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls
Vaginal pH >4.5
Positive whiff-amine test, defined as the presence of a fishy odor when a drop of 10 percent
potassium hydroxide (KOH) is added to a sample of vaginal discharge
Clue cells on saline wet mount (picture 1A-B). Clue cells are vaginal epithelial cells studded
with adherent coccobacilli that are best appreciated at the edge of the cell. For a positive
result, at least 20 percent of the epithelial cells on wet mount should be clue cells. The
presence of clue cells diagnosed by an experienced microscopist is the single most reliable
predictor of BV [45].
Mobiluncus species may be noted on microscopy as well (movie 1).
Using Gram's stain as the standard for diagnosing BV, the sensitivity of Amsel criteria for diagnosis
of BV is over 90 percent and specificity is 77 percent [46].

Gram's stain Gram's stain of vaginal discharge is the gold standard for diagnosis of BV (picture
2A-B) [47], but is mostly performed in research studies because it requires more time, resources,
and expertise than Amsel criteria [48-50]. The Gram-stained smear is evaluated using Nugent
criteria (table 2) or Hay/Ison criteria (table 3). If clinical criteria are used to define infection, then
reported sensitivity ranges from 62 to 100 percent [51].
Cytology The Papanicolaou smear is not reliable for diagnosis of BV (sensitivity 49 percent,
specificity 93 percent) [52]. No information is available on the sensitivity and specificity of liquidbased cervical cytology screening methods. If a cytology smear suggests BV (ie, shift in flora from
predominantly lactobacilli to predominantly coccobacilli with or without clue cells), the patient should
be asked about symptoms, and if symptomatic, she should undergo standard diagnostic testing for
BV and treatment, if appropriate. Treatment of asymptomatic women is not routinely indicated.
(See 'Asymptomatic infection' below.)
Culture Because BV represents complex changes in the vaginal flora, vaginal culture
has no role in diagnosis. Although cultures for G. vaginalis are positive in almost all women with
symptomatic infection, the organism is detected in up to 50 to 60 percent of healthy asymptomatic
women; thus, its presence alone is not diagnostic of BV.
Commercial tests Commercial tests for diagnosis of BV are not widely used, given the excellent
performance of Amsel criteria, but can be useful when microscopy is not available.
The Affirm VP III test is an automated DNA probe assay for detecting G. vaginalis when present at
a high concentration [53]. It takes less than one hour to perform and is the best option when
findings on physical examination suggest BV (characteristic vaginal discharge and results of pH and
whiff test, if available), but microscopy cannot be performed to look for clue cells. In one study, for
example, the combination of a positive DNA probe (concentration of G. vaginalis 2 times
107 CFU/mL) and vaginal pH >4.5 had a sensitivity and specificity of 95 and 99 percent,
respectively, for diagnosis of BV when clinical criteria were used as the diagnostic standard [54].
Not all studies have reproduced these excellent results, and over-diagnosis is possible.
The OSOM BVBlue system is a chromogenic diagnostic test based on the presence of elevated
sialidase enzyme activity in vaginal fluid samples. This enzyme is produced by bacterial pathogens
associated with bacterial vaginosis including Gardnerella, Bacteroides, Prevotella, and Mobiluncus.
The test can be performed at the point of care and results are available in 10 minutes (Clinical
Laboratory Improvement Amendments [CLIA]-waived). Sensitivity ranging from 88 to 94 percent
and specificity ranging from 91 to 98 percent have been reported when compared with Amsel and
Nugent criteria [55-57].
Investigational tests Quantitative polymerase chain reaction (PCR)-based assays are based
upon molecular quantification of G. vaginalis and Atopobium vaginae, and other bacteria [58,59].
Although these tests have good sensitivity and specificity compared with standard clinical tests [60],
they are expensive and of questionable advantage [61].
A urine test that uses fluorescence in situ hybridization (FISH) to identify the BV biofilm on
desquamated vaginal epithelial cells in urine sediment appears promising and is also under
investigation [11].

Diagnosis without speculum examination BV has been diagnosed using a swab of vaginal
discharge obtained by the patient or clinician without physical examination. However, omission of
the speculum examination results in under-diagnosis and should be avoided.
In one study, young women with or without vaginitis symptoms self-tested for BV using a pH
or sialidase test and results were compared with clinician-performed examination with clinical
diagnosis of BV by modified Amsel criteria [62]. Compared with diagnosis by clinician
examination, self-pH was 73 percent sensitive and 67 percent specific and self-sialidase was
40 percent sensitive and 90 percent specific.
In another study of the diagnostic accuracy for BV among women presenting with vaginal
discharge to a sexually transmitted diseases (STD) clinic, all women provided self-obtained
vaginal swabs for examination, completed a questionnaire, and then were examined by a
clinician [63]. A non-examining clinician reviewed the findings of the questionnaire and selfobtained vaginal swab and diagnosed BV if at least two of three Amsel criteria were positive
(pH>4.5, >20 percent clue cells, positive Whiff test). Examining clinicians diagnosed BV if at
least three of the four standard Amsel criteria were positive (characteristic discharge, pH >4.5,
>20 percent clue cells, positive Whiff test). In all cases, Gram-stained slides for diagnosis of
BV by Nugent criteria were made, but the results were not disclosed, and 125 were positive.
The investigators found that clinical examination with a speculum exam was more likely to
result in a correct diagnosis of BV than just examination of a self-obtained vaginal
swab (90/125 versus 68/125), but also resulted in over diagnosis/over treatment in 15 patients
(105 positive diagnoses versus 61 positive diagnoses).
DIFFERENTIAL DIAGNOSIS In the absence of microscopy, a lack of fishy odor (negative whiff
test) makes the diagnosis of bacterial vaginosis (BV) unlikely. BV is usually suspected because of
high vaginal pH (>4.5). Other causes of increased pH include trichomoniasis, atrophic vaginitis, and
desquamative inflammatory vaginitis. These four entities are easily distinguishable by clinical and
microscopic features.
Women with BV do not have dyspareunia or signs of vaginal inflammation; in contrast,
women with atrophic vaginitis, desquamative inflammatory vaginitis, and trichomoniasis
usually have these signs and symptoms.
Both atrophic vaginitis and desquamative inflammatory vaginitis are associated with an
increased number of parabasal cells on microscopy, which is not observed in women with BV.
A large number of polymorphonuclear leukocytes on microscopy are characteristic of
desquamative inflammatory vaginitis, trichomoniasis, and atrophic vaginitis with infection, but
not BV.
Visualization of trichomonads readily makes the diagnosis of trichomoniasis in the setting of
an elevated pH, however, in other cases, we suggest using more sensitive and specific
diagnostic tests to diagnose or exclude trichomoniasis.
CONSEQUENCES
Pregnant women with bacterial vaginosis (BV) are at higher risk of preterm delivery
(see 'Pregnant women' below) [64-67].
BV is a cause of [68-70]:
Endometrial bacterial colonization

Plasma-cell endometritis
Postpartum fever
Posthysterectomy vaginal cuff cellulitis
Postabortal infection
BV is a risk factor for human immunodeficiency virus (HIV) acquisition and transmission
[29,71,72].
BV is a risk factor for acquisition of herpes simplex virus type 2 (HSV-2), gonorrhea,
chlamydia, and trichomonas infection [73-75]. Although BV is more common among women
with pelvic inflammatory disease (PID), it is not clear whether it is a causal factor or an
independent risk factor for this disease [76,77].
It has been hypothesized that the increased risk of acquisition of sexually transmitted
infections in women with BV may be due to lack of hydrogen peroxide-producing lactobacilli in
the vaginal flora of affected women; other factors associated with BV infection, such as local
cytokine production, may also play a role.
BV may be a factor in development of precancerous cervical lesions. In a systematic review
and meta-analysis of primarily cross-sectional studies, the risk of cervical intraepithelial
neoplasia (CIN) or squamous intraepithelial lesions (SIL) was increased in women with BV
(OR 1.15, 95% CI 1.24-1.83); however, there was considerable heterogeneity among these
studies and both CIN 1 and low-grade SIL, which do not usually progress to cancer, were
included as outcomes [78]. BV appears conducive to the persistence of human papillomavirus
(HPV) infection [79,80], which is necessary but not sufficient for development of high grade
cervical lesions and cancer. (See "Cervical intraepithelial neoplasia: Terminology, incidence,
pathogenesis, and prevention", section on 'Role of human papillomavirus'.)
TREATMENT Bacterial vaginosis (BV) resolves spontaneously in up to one-third of nonpregnant
and one-half of pregnant women [81-84]. Treatment is indicated for relief of symptoms in women
with symptomatic infection and to prevent postoperative infection in those with asymptomatic
infection prior to abortion or hysterectomy. (See 'Gynecologic procedures' below.)
Treatment of BV may also reduce the risk of acquiring sexually transmitted diseases (STDs),
including human immunodeficiency virus (HIV) [29,85]. For this reason, some experts support the
concept of treating all women with BV regardless of presence or absence of symptoms; however,
we agree with the United States Centers for Disease Control and Prevention (CDC)
recommendations to not treat asymptomatic women.
Asymptomatic pregnant women with previous preterm births may also benefit, but screening and
treatment of these women is controversial. (See 'Pregnant women'below.)
The following treatment recommendations are consistent with those of the CDC [44]. Guidelines
from other organizations are available elsewhere [86,87].
Nonpregnant women
Drugs Metronidazole or clindamycin administered either orally or intravaginally results in a high
rate of clinical cure (70 to 80 percent at four weeks of follow-up) (table 4) [88-91]. Oral medication is
more convenient, but associated with a higher rate of systemic side effects than vaginal
administration. Tinidazole is a reasonable oral alternative. No new drugs have been introduced for
BV therapy in the past decade.

Metronidazole The efficacy of metronidazole has been established in randomized trials using
either placebo or active drug controls [91,92]. The oral regimen we recommend is 500 mg twice
daily for seven days [44]. Treatment with a single oral dose of 2 grams of metronidazole has lower
efficacy [93] and is no longer recommended for treatment of BV [44]. Alcohol should not be
consumed during therapy and for one day after completion of therapy.
There is little evidence of benefit from prolonging therapy longer than seven days. Most
comparative studies using divided-dose oral regimens for one week achieved early cure rates in
excess of 90 percent, and cure rates (by Amsel criteria) at four weeks of approximately 80 percent
[89,91,94-98]. Although early cure rates are significantly higher when the initial course
of metronidazole therapy is 14 days rather than 7 days, long-term cure rates (21 days after
completion of therapy) are similar for both treatment regimens [33]. Published cure rates vary widely
according to the investigators' diagnostic criteria, definition of cure and treatment failure, and length
of time post-therapy before the follow-up visit.
Vaginal therapy with 0.75 percent metronidazole gel 5 grams once daily for five days is as effective
as oral metronidazole (5 grams of gel contains 37.5 mg of metronidazole) [95,96,99,100]. The
choice of oral versus vaginal therapy should depend upon patient preference.
Side effects of metronidazole include a metallic taste, nausea (in 10 percent of patients), transient
neutropenia (7.5 percent), a disulfiram-like effect with alcohol, prolongation of International
Normalized Ratio (INR) in patients taking vitamin K antagonists (eg, warfarin), and peripheral
neuropathy. Gastrointestinal side effects are less common with vaginal administration [96]. Allergy
to metronidazole is uncommon; it manifests as rash, urticaria, pruritus, and rarely, anaphylaxis,
which can be successfully treated by oral desensitization [101].
Clindamycin The efficacy of clindamycin has been demonstrated in a meta-analysis of
randomized trials, both comparative and placebo controlled [91]. The preferred regimen is a sevenday course of 2 percent clindamycin cream vaginally (5 grams of cream containing 100 mg of
clindamycin phosphate), but may be less effective than the metronidazole regimens; nevertheless,
vaginal clindamycin cream is a reasonable therapeutic choice [44].
Alternative regimens include oral clindamycin (300 mg twice daily for seven days) or clindamycin
ovules (100 mg intravaginally once daily for three days) [44,102]. A one-day or single application of
clindamycin as a bioadhesive is another option (Clindesse). These regimens have not been studied
extensively and may have lower efficacy for eradicating BV.
Intravaginal clindamycin therapy has been associated with an increased prevalence of clindamycin
resistant anaerobic bacteria in the vagina posttreatment (17 percent of bacterial isolates before
versus 53 percent of isolates after therapy) [103]. This effect persisted in most women for at least
90 days after clindamycin treatment. In contrast, increased resistance to metronidazole was not
observed in women treated with that drug. Further investigation is required to determine the clinical
implications of these findings.
Clindamycin cream should not be used concurrently with latex condoms, which may be weakened.
Pseudomembranous colitis has been reported with both oral and topical clindamycin.
Tinidazole Tinidazole is a second generation nitroimidazole that is considered an alternative
regimen if metronidazole and clindamycin are unavailable or not tolerated [44]. It has a longer half-

life than metronidazole (12 to 14 hours versus 6 to 7 hours) and fewer side effects [104], but is more
costly since no generic formulation is available. If used, we suggest 1 gram orally once daily for five
days, as efficacy is slightly higher and side effects are slightly less frequent than with shorter course
therapy (tinidazole 2 grams orally daily for two days) [105]. Randomized trials have shown that it is
at least as effective as metronidazole, but not superior [105-109], and a single dose regimen
appears to be as effective as vaginal clindamycin cream [110].
Secnidazole Secnidazole is a nitroimidazole antibiotic not available in the United States, but
available internationally. In a randomized double-blind non-inferiority trial, a single 2 gram oral dose
of secnidazole was at least as effective as a seven-day course of 500
mg metronidazole administered orally twice daily, and was well tolerated [111]. A single 1 gram oral
dose of secnidazole appears to be as effective as the 2 gram dose [112].
Probiotics Probiotics (live microorganisms which confer a health benefit on the host when
administered in adequate amounts) have been used alone and as adjunctive therapy to antibiotics
for treatment of BV and prevention of relapse. Systemic reviews of trials of probiotics for treatment
of BV have not found sufficient evidence for or against efficacy [113,114]. Although some trials have
reported very promising results, we feel the results should be reproduced in more well-designed
and larger trials before use of this therapy is considered. In addition, further investigation is needed
to determine the optimum route of administration (oral or vaginal), which strains or combination of
strains are most effective (eg, Lactobacillus rhamnosus GR-1, Lactobacillus reuteri RC14, Lactobacillus acidophilus), and the dose and duration of use. The regulatory oversight and
quality of commercially available probiotics varies worldwide. In the United States, the content of
these products is not standardized and often of poor quality. The US Food and Drug Administration
(FDA) advises caution in using dietary supplements containing live bacteria or yeast in
immunocompromised patients, as patient death has been reported [115].
Less effective and ineffective therapies Triple-sulfa
creams, erythromycin, tetracycline, ampicillin, amoxicillin, lactic acid gel, acetic acid gel, ascorbic
acid,azithromycin, chlorhexidine, hydrogen peroxide, and povidone-iodine vaginal douches are
significantly less effective than metronidazole and clindamycin and should not be used [33,116122]. Cure rates with ampicillin and amoxicillin are mediocre.
Follow-up Follow-up is unnecessary if symptoms resolve [44].
Sexual partners
Male partners It is not necessary to treat male sexual partners of affected women, as there
is no strong evidence that the woman's response to therapy and risk of relapse are influenced
by treatment of her male sex partner(s) [44,123]. However, the available trials are flawed; welldesigned and larger trials should be performed to assess the efficacy of male partner
treatment [124].
Sexual intercourse appears to play a role in disease activity. Some studies have reported
reduced rates of recurrence when male sexual partners used condoms routinely during coitus
or when women remained abstinent [33,37,125-128].
Female partners Women with BV who have sex with women (WSW) should encourage
their partners to be aware of the signs and symptoms of BV, given the high risk of concordant
infection (25 to 50 percent [24]). In women with confirmed infection, treatment is indicated for

relief of symptoms. It has been hypothesized that behavioral interventions that reduce transfer
of vaginal fluid between female sex partners may be helpful (eg, cleaning sex toys between
use, use of gloves during digital-vaginal sex); however, a small randomized trial evaluating this
approach reported no reduction in BV persistence [129]. Further study is needed.
(See"Medical care of women who have sex with women", section on 'Sexually transmitted
diseases'.)
Relapse and recurrent infection Approximately 30 percent of patients with initial responses to
therapy have a recurrence of symptoms within three months [94] and more than 50 percent
experience a recurrence within 12 months [125]. The explanation for this high rate of recurrence is
unclear. Reinfection is possible, but recurrence more likely reflects a failure to eradicate the
offending organisms or to reestablish the normal protective vaginal flora dominated by lactobacillus.
Infections involving biofilms can be more difficult to eradicate [12]. The only interventions proven to
reduce development or recurrence of BV are chronic suppressive therapy and circumcision of male
partners [130,131].
Limited data are available regarding the optimal treatment strategy for women with recurrent BV
[44]. We suggest symptomatic relapse be treated initially with a seven-day course of oral or
vaginal metronidazole or clindamycin. The treatment regimen may be the same or different from the
initial or previous treatment regimen [44].
After initial induction therapy, most women with a history of recurrent infection benefit from
suppressive therapy to maintain an asymptomatic state. We believe any patient with more than
three documented episodes of BV in the previous 12 months should be offered a long-term
maintenance regimen consisting of maintenancemetronidazole gel. Longterm clindamycin regimens, oral or topical, are not advised because of toxicity and lack of
documented efficacy [37]. Accordingly, if any of the aforementioned antimicrobials fail, we prescribe
metronidazole gel 0.75 percent or an oral nitroimidazole for 7 to 10 days followed by twice weekly
dosing of gel for four to six months [44]. In one multicenter prospective trial of this metronidazole gel
regimen, recurrent BV occurred in 25.5 percent of patients on suppressive therapy versus 59.1
percent of those receiving placebo [130]. Secondary vaginal candidiasis was a common side effect.
Results can be improved by adding vaginal boric acid to the oral nitroimidazole induction therapy
[132]. Metronidazole or tinidazole is taken orally for seven days; vaginal boric acid 600 mg once
daily at bedtime is begun at the same time and continued for 21 days [44]. Patients are seen for
follow-up a day or two after their last boric acid dose; if they are in remission, we immediately begin
metronidazole gel twice weekly for four to six months as suppressive therapy. Therapy is then
discontinued. Boric acid can cause death if consumed orally; patients should be told to store
boric acid in a secure place that is inaccessible to children.
As discussed above, no study has demonstrated reduced rates of recurrence in women whose
partners were treated with metronidazole. However, some studies have reported reduced rates of
recurrence when sexual partners used condoms routinely with coitus or the patient remained
abstinent [33,37,125-128]. For this reason, some experts suggest these behavioral interventions for
women with recurrent infection.

A single trial has reported that use of condoms and combination metronidazole/nystatin ovule
therapy may reduce the frequency of recurrent infection [126]. The higher efficacy of the ovule may
be due to the higher content of metronidazole (500 mg) compared with the gel (37.5 mg).
Exogenous lactobacillus recolonization with 30 days of oral probiotic Lactobacillus rhamnosus GR-1
and Lactobacillus reuteri RC-14 in addition to seven days ofmetronidazole therapy has been
suggested, but there is minimal evidence of the efficacy of this approach [91,133]. These results
should be reproduced in other trials before use of this therapy is considered.
Vaginal acidifying agents, although popular and widely used, have no role in the treatment of acute
or chronic BV, as they have never been shown to enhance cure rates. Douching should be avoided.
Likewise, in a randomized trial, probiotics were not more effective than placebo for prevention of
relapse [37].
Asymptomatic infection Treatment of asymptomatic BV is typically avoided since patients often
spontaneously improve over a period of several months and any antibacterial therapy is often
followed by symptomatic vaginal yeast infection. This practice is supported by a double-blind,
placebo controlled trial of 54 women with asymptomatic BV who were randomly assigned to receive
intravaginal metronidazole or placebo gel [83]. There was no difference in the proportion of women
in either group who noticed improvement in vaginal odor or discharge. In addition, 6 of 28 women
receiving metronidazole developed symptomatic vaginal candidiasis compared with no women
taking placebo.
Although some experts recommend treatment of asymptomatic BV because affected women are
more susceptible to acquiring other STDs (including HIV and herpes simplex virus), available
evidence is insufficient to clearly support or exclude a benefit of treatment [85,134-136].
Treatment is indicated for asymptomatic women who are scheduled for certain gynecologic
procedures (see below). Treatment of asymptomatic infection in pregnant women is more complex
and is discussed in detail below. (See 'Pregnant women' below.)
Gynecologic procedures Evidence linking asymptomatic BV with gynecologic complications
has caused this issue to be reassessed, especially with the availability of topical therapy. It is
reasonable to treat asymptomatic BV prior to hysterectomy and before pregnancy termination to
prevent postprocedure infection (cuff infection after hysterectomy, endometritis after abortion).
Reported reductions in postoperative infectious complications range from 10 to 75 percent [137143].
Pregnant women
Symptomatic BV infection All women with symptomatic BV should be treated to relieve
bothersome symptoms. Oral treatment is effective and has not been associated with adverse fetal
or obstetrical effects [144-149]. The therapeutic options include [44]:
Metronidazole 500 mg orally twice daily for seven days
Metronidazole 250 mg orally three times daily for seven days
Clindamycin 300 mg orally twice daily for seven days
Some clinicians avoid use of metronidazole in the first trimester because it crosses the placenta,
and thus has a potential for teratogenicity. However, meta-analysis has not found any relationship

between metronidazole exposure during the first trimester of pregnancy and birth defects [150], and
the CDC no longer discourage the use of metronidazole in the first trimester [44]. An additional
concern is that the drug is mutagenic in bacteria and carcinogenic in mice, but there is no evidence
of harm in humans.
As mentioned above, topical therapy is as effective as oral therapy in the treatment of nonpregnant
women with BV. In contrast, some experts avoid topical therapy in pregnant women because they
believe oral treatment is more effective against potential subclinical upper genital tract infection
[151-153].
Asymptomatic infection and screening As many as one-third of pregnant women in the United
States have BV [64]. 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 1.563.00) [154]. The increased risk of preterm birth attributable to BV appears to be linked to preterm
labor due to chorioamnionitis [65,155]. Other complications of BV include postpartum endometritis
(OR 2.53, 95% CI 1.25-5.08), and an increased risk of late miscarriage (OR 6.32, 95% CI 3.6510.9) [154].
Despite the association between BV and adverse outcome, screening and treatment of
asymptomatic BV during pregnancy is controversial. Meta-analyses of randomized trials performed
in general obstetric populations have generally found that treatment of asymptomatic infection does
not reduce the incidence of preterm labor or delivery in the overall obstetrical population
[144,156,157], but some subgroups of women, such as those at high risk for preterm birth, may
benefit. The available evidence is discordant due to differences in selection of trials and differences
between the included trials.
In a 2013 Cochrane meta-analysis including 21 trials involving 7847 pregnant women with
BV (symptomatic or asymptomatic) detected through screening, antibiotic therapy was highly
effective in eradicating infection, but did not significantly reduce the odds of preterm birth at
less than 37 weeks (OR 0.88, 95% CI 0.71-1.09) or the risk of preterm premature rupture of
membranes (OR 0.74, 95% CI 0.30-1.84) [144]. Treatment initiated before 20 weeks of
gestation also did not reduce the risk of preterm birth before 37 weeks (OR 0.85, 95% CI 0.621.17).
When the Cochrane reviewers separately analyzed the subgroup of women with a history of
one or more prior preterm births (ie, women at high risk for preterm birth), the detection and
treatment of BV still did not significantly reduce the risk of preterm birth (OR 0.78, 95% CI
0.42-1.48; 3 trials, 421 women).
In 2008, the United States Preventive Services Task Force (USPSTF) evaluated the effect of
treatment of asymptomatic BV in women at high risk for preterm birth [156]. Due to
heterogeneity, results could not be pooled. Three trials showed fewer deliveries before 37
weeks of gestation with treatment, one showed no benefit, and one trial [158] reported an
increase in preterm deliveries after treatment with metronidazole. For delivery before 34
weeks of gestation, meta-analysis was possible and showed no significant treatment benefit.
In a 2011 meta-analysis of five randomized trials of asymptomatic women with BV at <22
weeks of gestation treated with clindamycin or placebo/no treatment, clindamycin therapy was
associated with a reduction in preterm birth <37 weeks (3.7 percent [44/1183] versus 6.2
percent [72/1163]; fixed effects RR 0.60, 95% CI 0.42-0.86, random effects 0.64, 95% CI 0.39-

1.05) and late miscarriage (0.3 percent [2/639] versus 1.9 percent [12/631]; RR 0.20, 95% CI
0.05-0.76) [157]. 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 0.200.76; vaginal RR 0.73, 95% CI 0.47-1.14). The analysis included a mixed population of women
at both low and high risk of preterm birth.
Based upon these data, we agree with the American College of Obstetricians and Gynecologists
(ACOG), USPSTF, and CDC recommendations to not routinely screen and treat all pregnant
women with asymptomatic BV to prevent preterm birth and its consequences [44,156,159]. It is not
possible to define specific features characterizing a subgroup of women who might respond
favorably to a screening and treatment protocol. Defining these features is an active area of
investigation.
As illustrated above, there may be benefits to early screening and treatment of asymptomatic
pregnant women who have a history of a previous preterm delivery, but there are insufficient data to
recommend this as a routine practice [146,160-163]. Further definition of high risk subgroups is
under investigation. As an example, women with polymorphisms of genes regulating cytokine
production (eg, tumor necrosis factor variants) have a greater proinflammatory immune response to
infectious stimuli, such as BV [164]. Enhanced induction of cytokines in these women could then
lead to preterm labor or rupture of membranes. Other aspects of host response (eg, low levels of
IgA to Gardnerella vaginalis) or the specific types of BV associated bacteria involved (eg, bacteria
that produce high levels of sialidase or protease) may also play a role in placing some women with
BV at high risk of preterm birth. (See "Risk factors for preterm labor and delivery", section on
'Infection' and "Risk factors for preterm labor and delivery", section on 'Genetic factors'.)
When treatment of BV is initiated, the optimal choice of antibiotic, timing of therapy, duration of use,
and harms of therapy are also controversial. The first trials demonstrated a reduction in preterm
birth in high risk women treated with oral metronidazole or oral metronidazole
and erythromycin (table 5) [151-153]. However, in two studies, metronidazole use in pregnancy
appeared to increase the risk of preterm birth [158,165]. This association requires further
investigation and confirmation before avoiding metronidazole for treatment of BV in pregnancy.
Other trials suggest that oral clindamycin given early in pregnancy is an effective therapy [157] and
that topical clindamycin given in the second half of pregnancy is less effective and even associated
with an increase in low birth weight and neonatal infection [166]. Therefore, we use oral therapy
when treatment is indicated, and consider both metronidazole and clindamycin acceptable choices.
Breastfeeding women Clindamycin has the potential to cause adverse effects on the breastfed
infant's gastrointestinal flora so the infant should be monitored for diarrhea, candidiasis (thrush,
diaper rash) or, rarely, blood in the stool indicating possible antibiotic-associated colitis [167]. Infant
side effects are less likely with vaginal than oral use since only about 30 percent of a vaginal dose
is absorbed.
When indicated, metronidazole is used for treatment of infection in neonates. There are no human
data supporting an association between metronidazole use and cancer; however, an association
with carcinogenesis in rodents has been demonstrated [168]. Outcomes data of maternal
metronidazole use did not show a significant increase in adverse events compared to use of other
antimicrobials, although a cohort study found a nonsignificant trend toward more loose stools and

more candidal colonization in metronidazole-exposed infants. Since the relative infant dose of
metronidazole is high (29 percent) with maternal administration of the 2 gram one-time dose, a
cautious approach for mothers receiving this dose is to express and discard their milk for 12 to 24
hours. This recommendation has not been extended to other metronidazole regimens.
Use of vaginal metronidazole has not been studied during breastfeeding. After vaginal
administration, plasma levels are less than 2 percent of those after a 500 mg oral dose, so vaginal
use of metronidazole during breastfeeding is unlikely to be of concern [168].
In lactating women who are administered tinidazole, interruption of breastfeeding is recommended
during treatment and for three days after the last dose based on animal data [44].
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 10 th 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.)
Basics topics (see "Patient information: Bacterial vaginosis (The Basics)")
Beyond the Basics topics (see "Patient information: Bacterial vaginosis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
Bacterial vaginosis (BV) is the most common cause of vaginitis in women of childbearing
age. (See 'Introduction' above.)
BV represents a complex change in the vaginal flora characterized by a reduction in
concentration of the normally dominant hydrogen-peroxide producing lactobacilli and an
increase in concentration of other organisms, particularly anerobic and highly specific
fastidious BV-associated bacteria. Vaginal wall biofilms, comprised predominantly
of Gardnerella vaginalis, appear to play a role in pathogenesis. (See 'Pathogenesis and
microbiology' above.)
Approximately 50 to 75 percent of women with BV are asymptomatic. Those with symptoms
often present with an off-white, thin, and homogeneous "fishy smelling" discharge that is more
noticeable after coitus and during menses. (See 'Clinical features' above.)
Sequelae of BV can include an increased risk of preterm birth, plasma-cell endometritis,
postpartum fever, post-hysterectomy vaginal cuff cellulitis, postabortal infection, pelvic
inflammatory disease, and acquisition of other sexually transmitted infections.
(See 'Consequences' above.)
Diagnosis

When microscopy is available, the diagnosis of BV is based on the presence of at least three
of the following four Amsel criteria (see 'Diagnosis' above):
Homogeneous, thin, grayish-white discharge that smoothly coats the vaginal walls
Vaginal pH greater than 4.5
Positive whiff-amine test, defined as the presence of a fishy odor when 10 percent
potassium hydroxide (KOH) is added to a sample of vaginal discharge
Clue cells on saline wet mount, comprising at least 20 percent of epithelial cells
If microscopy is not available, we suggest using physical examination, pH testing, whiffamine test, and a commercial test using a DNA probe (eg, Affirm VP III) to make the diagnosis
of BV. (See 'Commercial tests' above.)
Vaginal culture is not useful. (See 'Culture' above.)
Treatment of nonpregnant women
Treatment of symptomatic women with bacterial vaginosis is indicated to reduce vaginal
discharge and odor. We recommend metronidazole or clindamycin (Grade 1A)
(see 'Treatment' above). Options include:
Metronidazole 500 mg twice daily orally for seven days
Metronidazole gel 0.75 percent (5 grams containing 37.5 mg metronidazole) once daily
vaginally for 5 days
Clindamycin 2% vaginal cream once daily at bedtime for seven days
Clindamycin 300 mg twice per day orally for seven days
Clindamycin 100 mg vaginal suppositories at bedtime for three days
Clindamycin bioadhesive cream (Clindesse) 2% as a single vaginal dose of 5 grams of
cream containing 100 mg of clindamycin phosphate.
During therapy with metronidazole, alcohol should not be consumed. During therapy
with clindamycin cream, latex condoms should not be used. (See'Metronidazole' above
and 'Clindamycin' above.)
We recommend not treating sexual partners of women with BV (Grade 1B). (See 'Sexual
partners' above.)
Approximately 30 percent of patients with an initial response to therapy have a recurrence of
symptoms within three months and more than 50 percent experience a recurrence within 12
months. We treat symptomatic relapse with a longer course of therapy, using a different
antibiotic than that used for the initial episode. For women who prefer preventive therapy
instead of treatment of frequent episodes of BV, we suggest metronidazole or tinidazole orally
for seven days; vaginal boric acid 600 mg is begun at the same time and continued for 21
days (Grade 2B). Patients are seen for follow-up a day or two after their last boric acid dose; if
they are in remission, we immediately begin metronidazole gel twice weekly for four to six
months as suppressive therapy. (See 'Relapse and recurrent infection'above.)
We suggest treatment of asymptomatic women who are to undergo hysterectomy (Grade
2B). Preoperative treatment decreases the frequency of postoperative infectious
complications. (See 'Gynecologic procedures' above.)
Treatment of pregnant women

Pregnant women with BV are at increased risk of preterm birth. We recommend not
screening all pregnant women for BV, given there is no evidence that screening and treatment
of asymptomatic infection reduces the risk of preterm birth (Grade 1A). (See 'Asymptomatic
infection and screening' above.)
We treat pregnant women with symptomatic BV infection to relieve symptoms. We
prescribe clindamycin 300 mg orally twice daily for seven days or metronidazole500 mg orally
twice daily for seven days. (See 'Symptomatic BV infection' above.)
We suggest treatment of asymptomatic women who are to undergo pregnancy termination
(Grade 2B). Preoperative treatment decreases the frequency of postoperative infectious
complications. (See 'Gynecologic procedures' above.)
Use of UpToDate is subject to the Su

Candida
INTRODUCTION Vulvovaginal candidiasis refers to a disorder characterized by signs and
symptoms of vulvovaginal inflammation in the presence of Candidaspecies. It is the second most
common cause of vaginitis symptoms (after bacterial vaginosis) and accounts for approximately
one-third of vaginitis cases [1]. In contrast to oropharyngeal candidiasis, it is generally not
considered an opportunistic infection, and, unlike trichomonas vaginitis, it is not considered a
sexually transmitted disease.
PREVALENCE Candida species can be identified in the lower genital tract in 10 to 20 percent of
healthy women in the reproductive age group, 6 to 7 percent of menopausal women, and 3 to 6
percent of prepubertal girls [2,3]. However, identification of vulvovaginal Candida is not necessarily
indicative of candidal disease, as the diagnosis of vulvovaginitis requires the presence of
vulvovaginal inflammation.
The prevalence of vulvovaginal candidiasis is difficult to determine because the clinical diagnosis is
often based on symptoms and not confirmed by microscopic examination or culture (as many as
one-half of clinically diagnosed women may have another condition [4]). In addition, the widespread
use of over-the-counter antimycotic drugs makes epidemiologic studies difficult to perform and
culture without clinical correlation is likely to overestimate the prevalence of disease.
In surveys, the prevalence of vulvovaginal candidiasis is highest among women in their reproductive
years: 55 percent of female university students report having had at least one healthcare providerdiagnosed episode by age 25 years, 29 to 49 percent of premenopausal women report having had
at least one lifetime episode, and 9 percent of women report having had four or more infections in a
12-month period (ie, recurrent vulvovaginal candidiasis [RVVC]) [5,6]. In women with an initial
infection, the probability of RVVC was 10 percent by age 25 years, and 25 percent by age 50 years
[6].
The prevalence increases with age up to menopause and is higher in African-American women than
in other ethnic groups. The disorder is uncommon in postmenopausal women, unless they are
taking estrogen therapy. It is also uncommon in prepubertal girls, in whom it is frequently
overdiagnosed.

MICROBIOLOGY Candida albicans is responsible for 80 to 92 percent of episodes of

vulvovaginal candidiasis [7] and C. glabrata accounts for almost all of the remainder [8]. Some, but
not all, investigators have reported an increasing frequency of non-albicans species, particularly C.
glabrata [9,10], possibly due to widespread use of over-the-counter drugs, long-term use of
suppressive azoles, and the use of short courses of antifungal drugs.
All Candida species produce similar vulvovaginal symptoms, although the severity of symptoms is
milder with C. glabrata and C. parapsilosis.
In contrast to bacterial vaginosis, vulvovaginal candidiasis is not associated with a reduction in
vaginal lactobacilli [11-14].
PATHOGENESIS Candida organisms probably access the vagina via migration from the rectum
across the perianal area [15]; cultures of the gastrointestinal tract and vagina often show
identical Candida species. Less commonly, the source of infection is sexual or relapse from a
vaginal reservoir.
Symptomatic disease is associated with an overgrowth of the organism and penetration of
superficial epithelial cells [16-18]. The mechanism by which Candida species transform from
asymptomatic colonization to an invasive form causing symptomatic vulvovaginal disease is
complex, involving host inflammatory responses and yeast virulence factors. (See "Biology of
Candida infections".)
Recurrent vulvovaginal candidiasis Recurrent vulvovaginal candidiasis is defined as four or
more episodes of symptomatic infection within one year [16]. Longitudinal DNA-typing studies
suggest that, in most women, recurrent disease is due to relapse from a persistent vaginal reservoir
of organisms or endogenous reinfection with the identical strain of susceptible C. albicans [19,20].
Rarely, infection is due to a different Candida species.
Recurrent vulvovaginal candidiasis has been associated with decreased in vivo concentration of
mannose binding lectin (MBL) and increased concentration of interleukin-4. Two specific gene
polymorphisms, variants in the MBL and interleukin-4 alleles, can account for this finding in some
women. The prevalence of a variant MLB gene is higher in women with recurrent vulvovaginal
candidiasis than in controls without candidiasis [21,22]. Since the direct interaction of MBL with C.
albicans is an important component of the host's ability to resist candidiasis, impairment of this
interaction in MBL-deficient individuals, such as those with certain MBL polymorphisms, appears to
predispose these women to recurrent vulvovaginal candidal infection [21,23-26]. These women
mount a strong inflammatory response when exposed to small amounts of Candida, whereas
normal women may not mount any inflammatory response and remain asymptomatic. Interleukin-4
blocks the anti-Candida response mediated by macrophages, thus elevated IL-4 levels result in
inhibition of local defense mechanisms.
RISK FACTORS Sporadic attacks of vulvovaginal candidiasis usually occur without an
identifiable precipitating factor. Nevertheless, a number of factors predispose to symptomatic
infection [27,28]:
Diabetes mellitus Women with diabetes mellitus who have poor glycemic control are
more prone to vulvovaginal candidiasis than euglycemic women [29,30]. In particular, women
with Type 2 diabetes appear prone to non-albicans Candida species [31].

Antibiotic use Use of broad spectrum antibiotics significantly increases the risk of
developing vulvovaginal candidiasis [32]. As many as one-quarter to one-third of women
develop the disorder during or after taking these antibiotics because inhibition of normal
bacterial flora favors growth of potential fungal pathogens, such as Candida. Administration
of lactobacillus (oral or vaginal) during and for four days after antibiotic therapy does not
prevent postantibiotic vulvovaginitis [33].
Increased estrogen levels Vulvovaginal candidiasis appears to occur more often in the
setting of increased estrogen levels, such as oral contraceptive use (especially when estrogen
dose is high), pregnancy, and estrogen therapy.
Immunosuppression Candidal infections are more common in immunosuppressed
patients, such as those taking glucocorticoids or other immunosuppressive drugs, or with
human immunodeficiency virus (HIV) infection [34].
Contraceptive devices Vaginal sponges, diaphragms, and intrauterine devices have
been associated with vulvovaginal candidiasis, but not consistently. Spermicides are not
associated with Candida infection.
Behavioral factors Vulvovaginal candidiasis is not traditionally considered a sexually
transmitted disease (STD) since it occurs in celibate women and sinceCandida species are
considered part of the normal vaginal flora. This does not mean that sexual transmission
of Candida does not occur or that vulvovaginal candidiasis is not associated with sexual
activity. For example, an increased frequency of vulvovaginal candidiasis has been reported at
the time most women begin regular sexual activity [5,27,35]. In addition, partners of infected
women are four times more likely to be colonized than partners of uninfected women, and
colonization is often the same strain in both partners. However, the number of episodes of
vulvovaginal candidiasis a woman has does not appear to be related to her lifetime number of
sexual partners or the frequency of coitus [27,36,37].
The type of sex may be a factor. Infection may be linked to orogenital and, less commonly,
anogenital sex. Evidence of a link between vulvovaginal candidiasis and hygienic habits (eg,
douching, use of tampons/menstrual pads) or wearing tight or synthetic clothing is weak and
conflicting [27,38-45].
Recurrent vulvovaginal candidiasis The risk factors described above are apparent in only a
minority of women with recurrent disease (see 'Risk factors' above). In the remainder, factors that
predispose to recurrent infection likely involve abnormalities in local vaginal mucosal immunity [46]
and genetic susceptibility (see 'Recurrent vulvovaginal candidiasis' above).
The role of sexual transmission in recurrent infection remains unresolved, but does not appear to be
a major factor as the bulk of evidence from randomized trials doesnot support treatment of sexual
partners [47-50].
CLINICAL FEATURES Vulvar pruritus is the dominant feature of vulvovaginal candidiasis
[8,17,51-53]. Vulvar burning, soreness, and irritation are also common, and can be accompanied by
dysuria (typically perceived to be external or vulvar rather than urethral) or dyspareunia. Symptoms
are often worse during the week prior to menses [53]. The intensity of signs and symptoms varies
from mild to severe, except among women with C. glabrata or C. parapsilosis infection, who tend to
have mild or minimal clinical findings [54].

Physical examination of the external genitalia, vagina, and cervix often reveals erythema of the
vulva and vaginal mucosa and vulvar edema. Vulvar excoriation and fissures are present in about
one-quarter of patients. There can be little or no discharge; when present, it is classically white,
thick, adherent, and clumpy (curd-like or cottage cheese-like) with no or minimal odor. However, the
discharge may be thin and loose, watery, homogeneous, and indistinguishable from that in other
types of vaginitis. The cervix usually appears normal.
DIAGNOSIS The general diagnostic approach to women with vaginal complaints is reviewed
separately. (See "Approach to women with symptoms of vaginitis".)
The diagnosis of vulvovaginal candidiasis is based on the presence of Candida on wet mount,
Grams stain, or culture of vaginal discharge in a woman with characteristic clinical findings (eg,
vulvovaginal pruritus, burning, erythema, edema, and/or curd like discharge attached to the vaginal
sidewall) and no other pathogens to account for her symptoms. (See 'Clinical features' above.)
Because none of the clinical manifestations of vulvovaginal candidiasis is pathognomonic,
suspected clinical diagnosis should always be confirmed by laboratory methods. Importantly,
although vulvar pruritus is a cardinal symptom of the disorder, less than 50 percent of women with
genital pruritus have vulvovaginitis candidiasis [55].
Office diagnosis The vaginal pH in women with Candida infection is typically normal (4 to 4.5),
which distinguishes candidiasis from trichomoniasis or bacterial vaginosis (table
1). Candida species can be seen on a wet mount of the discharge; adding 10 percent potassium
hydroxide destroys the cellular elements and facilitates recognition of budding yeast,
pseudohyphae, and hyphae (picture 1 and picture 2 and picture 3 and picture 4 and picture
5 and picture 6) [56]. Use of Swartz-Lamkins fungal stain (potassium hydroxide, a surfactant, and
blue dye) may facilitate diagnosis by staining the Candida organisms blue so they are easier to
identify [57]. However, microscopy is negative in up to 50 percent of patients with culture confirmed
vulvovaginal candidiasis [16].
Microscopy is also important for looking for clue cells or motile trichomonads, which indicate
bacterial vaginosis and trichomoniasis, respectively, as alternative diagnoses, co-infection, or mixed
vaginitis [58].
Role of culture We recommend not culturing all patients because culture is not necessary for
diagnosis if microscopy shows yeast, and it is costly, delays the time to diagnosis by several days,
and may be positive due to colonization rather than infection.
We obtain a culture in:
Women with clinical features of vulvovaginal candidiasis, normal vaginal pH, and no
pathogens (yeast, clue cells, trichomonads) visible on microscopy. A positive culture in these
patients confirms the diagnosis and reveals the species of Candida, thus avoiding empiric, unindicated or incorrect therapy.
Women with persistent or recurrent symptoms because many of these women have nonalbicans infection resistant to azoles (see 'Diagnosis of recurrent vulvovaginal
candidiasis' below).
To perform a culture, a vaginal sample is obtained from the lateral wall using a cotton tipped swab
and inoculated onto Sabouraud agar, Nickerson's medium, or Microstix-candida medium; these

media perform equally well [8]. Culture for Candida does not require quantification of in vitro colony
count. Speciation of Candida is not essential for primary diagnostic testing as most isolates
are Candida albicans; however, species identification is essential in refractory and recurrent
disease. Laboratory techniques for identification of multiple Candida species are reviewed
separately. (See "Biology of Candida infections", section on 'Detection in the microbiology
laboratory'.)
Other tests There are no reliable point of care tests for Candida available in the United States
[59-64]. A DNA probe test performed in a centralized laboratory offers results comparable to culture
with results available in several hours, but no speciation (Affirm VPIII).
Polymerase chain reaction (PCR) methods have high sensitivity and specificity and a shorter turnaround time than culture [65-68], but are costly and offer no proven benefit over culture in
symptomatic women [65].
Pap smear is positive in 25 percent of patients with culture positive, symptomatic vulvovaginal
candidiasis [8]. It is insensitive because the cells are derived from the cervix, which is not affected
by Candida vaginitis. Treatment of Candida on a Pap smear of an asymptomatic woman is not
indicated (see 'Treatment' below).
Self diagnosis Self-diagnosis of vulvovaginal candidiasis is frequently inaccurate and should be
discouraged [69,70]. In a study that administered a questionnaire to 600 women to assess their
knowledge of the symptoms and signs of vulvovaginal candidiasis (and other infections) after
reading classic case scenarios, only 11 percent of women without a previous diagnosis of
vulvovaginal candidiasis correctly diagnosed this infection [69]. Women who had had a prior
episode were more often correct (35 percent), but were likely to use over-the-counter drugs
inappropriately to treat other, potentially more serious, gynecologic disorders.
In another report, the actual diagnoses in 95 women who self-diagnosed vulvovaginal candidiasis
were: vulvovaginal candidiasis (34 percent), bacterial vaginosis (19 percent), mixed vaginitis (21
percent), normal flora (14 percent), trichomonas vaginitis (2 percent), and other (11 percent) [70].
Women with a previous episode of vulvovaginal candidiasis and those who read the package insert
for their over-the-counter medication were not more accurate in making a diagnosis than other
women.
Some consequences of misdiagnosis and inappropriate therapy include a delay in correct diagnosis
and treatment, wasted monetary expenditure, and precipitation of vulvar dermatitis.
Diagnosis of recurrent vulvovaginal candidiasis Recurrent vulvovaginal candidiasis is
defined as four or more episodes of symptomatic infection within one year [16]. Vaginal cultures
should always be obtained to confirm the diagnosis and identify less common Candida species, if
present. As discussed above, recurrent disease is usually due to relapse from a persistent vaginal
reservoir of organisms or endogenous reinfection with identical strains of susceptible C.
albicans [19]; however, rarely, a new strain of Candida is responsible for the infection.
Testing for HIV infection Vulvovaginal candidiasis occurs more frequently and has greater
persistence, but not greater severity, in human immunodeficiency virus (HIV)-infected women with
very low CD4 counts and high viral load; however, this population is likely to manifest other acquired
immune deficiency syndrome (AIDS)-related sentinel conditions [34]. HIV testing of women only for

the indication of recurrent vulvovaginal candidiasis is not justified, given that

recurrent Candida vaginitis is a common condition in women without HIV infection and the majority
of cases occur in uninfected women. The microbiology of vulvovaginal candidiasis in HIV-infected
women is similar to that in HIV-negative women [8].
Women with risk factors for acquisition of HIV should be counseled and offered screening. These
risk factors are described in detail separately. (See "Screening for sexually transmitted infections".)
Differential diagnosis Other conditions to be considered in the differential diagnosis of
vulvovaginitis with normal vaginal pH include hypersensitivity reactions, allergic or chemical
reactions, and contact dermatitis. These conditions are discussed in detail elsewhere. Recognizing
local adverse reactions to topical agents is important; otherwise, additional topical agents, including
high potency corticosteroids, are often prescribed empirically and further aggravate symptoms.
(See "Dermatitis of the vulva".) Mechanical irritation due to insufficient lubrication during coitus can
also result in vaginal discomfort.
If vaginal pH exceeds 4.5 or excess white cells are present, mixed infection with bacterial vaginosis
or trichomoniasis may be present. Mixed infection (2 pathogens and all are symptomatic) is
estimated to occur in <5 percent of patients; coinfection (2 pathogens but some are not
symptomatic) is more common: 20 to 30 percent of women with bacterial vaginosis are co-infected
with Candida species [58]. (See "Bacterial vaginosis" and "Trichomoniasis".)
TREATMENT Treatment is indicated for relief of symptoms. Ten to 20 percent of reproductive
age women who harbor Candida species are asymptomatic; these women do not require therapy
[56].
The treatment regimen is based on whether the woman has an uncomplicated infection (90 percent
of patients) or complicated infection (10 percent of patients). Criteria are listed in the table (table 2).
Uncomplicated infections usually respond to treatment within a couple of days. Complicated
infections require a longer course of therapy and may take two weeks to fully resolve.
Treatment of sexual partners is unnecessary. There is no medical contraindication to sexual
intercourse during treatment, but it may be uncomfortable until inflammation improves.
Uncomplicated infection Criteria for uncomplicated infection include all of the following [17]:
Sporadic, infrequent episodes (3 episodes/year)
Mild to moderate signs/symptoms
Probable infection with Candida albicans
Healthy, nonpregnant woman
A variety of oral and topical preparations, many available over-the-counter and in single-dose
regimens, is available for the treatment of uncomplicated vulvovaginal candidiasis (table 3) [71]. In
randomized trials, oral and topical antimycotic drugs achieved comparable clinical cure rates, which
are in excess of 90 percent; short-term mycologic cure is slightly lower (70 to 80 percent) [72-75].
Studies that have assessed patient preference consistently reported a preference for the
convenience of oral treatment [73]. However, topical treatments have fewer side effects (eg,
possible local burning or irritation), while oral medication may cause gastrointestinal intolerance,
headache, rash, and transient liver function abnormalities. In addition, oral medications take a day
or two longer than topical therapy to relieve symptoms. The absence of superiority of any

formulation, agent, or route of administration suggests that cost, patient preference, and
contraindications are the major considerations in the decision to prescribe an anti-fungal for oral or
topical administration [75].
We suggest use of oral fluconazole, given that most women consider oral drugs more convenient
than those applied intravaginally. Fluconazole maintains therapeutic concentrations in vaginal
secretions for at least 72 hours after the ingestion of a single 150 mg tablet [76]. Side effects of
single-dose fluconazole (150 mg) tend to be mild and infrequent. However, fluconazole interacts
with multiple drugs; therefore, the potential for drug interactions should be addressed when
prescribing this agent. Since fluconazole is now available in a generic form, a single dose regimen
of fluconazole is less expensive than over-the-counter topical antifungals.
Azole resistance has only been reported in one case of vaginitis caused by C. albicans [77]. Thus,
in vitro susceptibility tests are rarely indicated unless compliant patients with a culture-proven
diagnosis have no response to adequate therapy.
Complicated infections Characteristics of complicated infections include one or more of the
following criteria [17]:
Severe signs/symptoms
Candida species other than C. albicans, particularly C. glabrata
Pregnancy, poorly controlled diabetes, immunosuppression, debilitation
History of recurrent (4/year) culture-verified vulvovaginal candidiasis
The treatment of complicated infection is summarized in the table and described in more detail
below (table 4).
Severe symptoms or compromised host Women with severe inflammation or host factors
suggestive of complicated infection need longer courses of oral or topical antimycotic drugs. It is
unknown whether one route is more effective than the other, as comparative trials of topical versus
oral treatment of complicated infection have not been performed.
Given the convenience of oral therapy, we suggest fluconazole (150 mg orally) for two to three
sequential doses 72 hours apart for treatment of complicated infections, depending on the severity
of the infection (table 4) [75]. The efficacy of this approach was supported by a trial that randomly
assigned 556 women with severe or recurrent candidiasis to therapy with a single dose of
fluconazole (150 mg) or two sequential doses given three days apart [78]. Severity of disease was
based upon a scoring system involving degree of pruritus and physical signs (erythema,
edema, excoriation/fissure formation). The two-dose regimen resulted in significantly higher
clinical cure/improvement rates at evaluation on day 14 (94 versus 85 percent) and day 35 (80
versus 67 percent) in women with severe, but not recurrent, disease. However, the response to
therapy was lower in the 8 percent of women infected with non-albicans Candida.
If the patient prefers topical therapy, observational series report that complicated patients require 7
to 14 days of topical azole therapy (eg, clotrimazole, miconazole,terconazole) rather than a one- to
three-day course [75,79].
For severe Candida vulvar inflammation (vulvitis), low potency topical corticosteroids can be applied
to the vulva for 48 hours until the antifungals exert their effect.

C. glabrata C. glabrata has low vaginal virulence and rarely causes symptoms, even when
identified by culture. Every effort should be made to exclude other co-existent causes of symptoms
and only then treat for C. glabrata vaginitis. Treatment failure with azoles is common (around 50
percent) in patients with C. glabratavaginitis [54]. Moderate success (65 to 70 percent) in women
infected with this organism can be achieved with intravaginal boric acid (600 mg capsule once daily
at night for two weeks) [54,80]. Better results (>90 percent cure) have been achieved with
intravaginal flucytosine cream (5 g nightly for two weeks) [80]. Neither boric acid capsules nor
flucytosine cream is available commercially and must be made by a compounding pharmacy. Boric
acid capsules can be fatal if swallowed.
There are no good data regarding use of oral voriconazole for C. glabrata vaginitis. Anecdotal
reports suggest poor response and rare cures, and the potential for toxicity.
There are also no good data on the efficacy of nystatin, which is available as a pessary in some
parts of the world. One or two pessaries of 100,000 units nystatin are inserted into the vagina
nightly for 14 days [81]. Alternatively, a suppository can be prepared by a compounding pharmacy.
Potential side effects include burning, redness, and irritation.
C. krusei Candida krusei is usually resistant to fluconazole, but is highly susceptible to topical
azole creams and suppositories, such as clotrimazole, miconazole, and terconazole. We treat for 7
to 14 days. It is also likely to respond to oral itraconazole or ketoconazole, but these oral agents
have variable toxicity so topical therapy is advised for first-line therapy. Idiosyncratic hepatotoxicity
secondary to ketoconazole therapy is a concern, but rare in this setting. In vitro susceptibility testing
is indicated in compliant patients with culture-proven diagnosis of C. krusei and no response to a
conventional course of one of these non-fluconazole therapies.
Pregnancy Treatment of pregnant women is primarily indicated for relief of symptoms. Vaginal
candidiasis is not associated with adverse pregnancy outcomes [82]. We suggest application of a
topical imidazole (clotrimazole or miconazole) vaginally for seven days [79,83]. There is less
information about the pregnancy safety profile of terconazole, a triazole, than for imidazoles.
Vaginal nystatin is another option. As discussed above, a pessary is available in some parts of the
world. One or two pessaries of 100,000 units nystatin are inserted into the vagina nightly for 14
days [81]. Alternatively, a suppository can be prepared by a compounding pharmacy. Potential side
effects include burning, redness, and irritation.
Administration of oral azoles during the first trimester is not recommended, as case reports have
described a pattern of birth defects (abnormalities of cranium, face, bones, and heart) after first
trimester exposure to high dose therapy (400 to 800 mg/day) [84,85]. The magnitude of the
teratogenic risk is unknown. First trimester use of a single, low dose of fluconazole 150 mg to treat
vaginal yeast infection has not been associated with an increased risk of birth defects overall in one
large epidemiologic study (7352 pregnancies) [86] and in several smaller epidemiologic studies [8792]. In the large nationwide cohort study, there was no overall risk of embryopathy associated with
exposure to cumulative fluconazole doses of 150, 300, or 350 to 6000 mg during the first trimester
nor with exposure to oral itraconazole or ketoconazole[86]. Although these data are reassuring for
women who took fluconazole before realizing that they were pregnant, an increased risk of specific
anomalies cannot be definitively excluded. Since vaginal administration is an effective alternative to
oral administration, the vaginal route is preferable to the oral route in pregnancy, especially the first
trimester, until more data are available supporting the safety of low dose oral administration.

Although treatment of vaginal Candida colonization in healthy pregnant women is unnecessary, in

Germany treatment is recommended in the third trimester because the rate of oral thrush and
diaper dermatitis in mature healthy newborns is significantly reduced by maternal treatment [55].
Recurrent infection The treatment of women with recurrent infections can be difficult and
frustrating [93]. Recurrent vulvovaginal candidiasis is defined as four or more episodes of
symptomatic candidal vaginitis in a 12-month period [79,93]. Attempts should be made to eliminate
or reduce risk factors for infection if present (eg, improve glycemic control, switch to lower estrogen
dose oral contraceptive). Although not based upon data from randomized trials, implementing a
change in one or more behavioral factors (eg, avoidance of panty liners, pantyhose, cranberry juice,
sexual lubricants) to see if there is improvement may be beneficial in rare women [38]. Management
of sexual dysfunction and the marital discord that frequently accompany chronic vaginitis should
also be addressed.
Decreasing gastrointestinal Candida colonization by oral administration of nystatin does not prevent
recurrent symptomatic vaginal infection [16].
Azoles Randomized trials comparing different therapeutic regimens have not been performed.
Based on the data cited below and personal experience, we believe that the optimal therapy for
recurrent vulvovaginal candidiasis in nonpregnant women consists of initial induction therapy
with fluconazole 150 mg every 72 hours for three doses, followed by maintenance fluconazole
therapy once per week for six months [94]. Therapy is then discontinued, at which point some
patients achieve a prolonged remission, while others relapse. A short-term relapse, with culture
confirmation of the diagnosis, merits reinduction therapy with three doses of fluconazole, followed
by repeat weekly maintenance fluconazole therapy, this time for one year. A minority of women
persist in relapsing as soon as fluconazole maintenance is withdrawn (fluconazole dependent
recurrent vulvovaginal candidiasis). Symptoms in these patients can be controlled by months or
years of weekly fluconazole.
Given the safety profile of low dose fluconazole, most experts do not suggest any laboratory
monitoring; however, if other oral imidazoles (ketoconazole, itraconazole) are used, particularly if
taken daily, then monitoring liver function tests is recommended. Idiosyncratic hepatotoxicity
secondary to ketoconazole therapy is a concern, but rare in this setting.
Although drug interactions are reported with fluconazole and several oral agents
(eg, warfarin, rifampin), such interactions are extremely unlikely with maintenance fluconazole due
to the low plasma concentrations accompanying the once weekly 150 mg dosing regimen.
Accordingly, no additional testing needed.
Alternative approaches that have been suggested include:
Treat each recurrent episode as an episode of uncomplicated infection (table 3) [79]
Treat each recurrent episode with longer duration of therapy (eg, topical azole for 7 to 14
days or fluconazole 150 mg orally on day 1, day 4, and day 7) [79]
The Infectious Diseases Society of America (IDSA) recommends 10 to 14 days of induction
therapy with a topical or oral azole, followed by fluconazole 150 mg once per week for six
months (clotrimazole 200 mg vaginal cream twice weekly is a nonoral alternative) [75].

Evidence for suppressive therapy Multiple observational studies of nonpregnant women with
recurrent vulvovaginal candidiasis have shown that antifungal maintenance suppressive therapy
taken for six months after an initial induction regimen resulted in negative cultures [72,95]. The best
available option in nonpregnant women is fluconazole 150 mg orally once per week for six months
[75]. However, maintenance therapy is only effective for preventing recurrent infection as long as
the medication is being taken. This was illustrated in a trial of 387 women with recurrent
vulvovaginal candidiasis treated with open-label fluconazole (150 mg orally at 72-hour intervals for
three doses) and then randomly assigned to weekly doses of fluconazole (150 mg) or placebo for
six months [94]. The maintenance therapy phase was begun two weeks after initiation of treatment
in patients who were clinically cured. Study drugs were discontinued in patients diagnosed with
recurrent candidal infection during follow-up visits.
The proportion of women who remained disease-free was significantly higher in
the fluconazole group (91 versus 36 percent at 6 months, 73 versus 28 percent at 9 months,
and 43 versus 22 percent at 12 months).
The mean time to recurrence in the fluconazole and placebo groups was 10.2 and 4.0
months, respectively.
Resistant isolates of C. albicans or superinfection with C. glabrata were not observed.
Although this regimen of maintenance fluconazole was convenient, safe, and as effective as other
therapies, long-term cure of recurrent vulvovaginal candidiasis was not achieved in one-half of the
women studied. Episodes of recurrent candidiasis resumed when maintenance therapy was
discontinued.
Fluconazole resistance In women with recurrent vulvovaginal candidiasis, there is some
evidence that frequent and prolonged use of fluconazole can infrequently select for fluconazole
resistance in C. albicans strains previously susceptible to fluconazole, which limits the options
available for treating these women. In a study of 25 women with refractory Candida vaginitis and
a C. albicans isolate with fluconazole minimum inhibitory concentration (MIC)
2 micrograms/mL, those with fluconazole MIC values of 2 or 4 micrograms/mL were treated
successfully by increasing fluconazole dosage to 200 mg twice weekly [96]. In the authors
experience, a higher dose of fluconazole was not effective for women with MIC 8 micrograms/mL.
These women should be evaluated for cross-resistance to itraconazole andketoconazole, as some
patients can be treated effectively with long-term maintenance daily imidazole therapy. However,
use of itraconazole or ketoconazole requires intermittent hepatic function testing. Idiosyncratic
hepatotoxicity secondary to ketoconazole therapy is a concern, but rare in this setting.
Women with severe recurrent vulvovaginal candidiasis infection and high-level pan azole resistance
do not have options other than topical boric acid (see 'Boric acid'below) or nystatin suppositories
[97].
In women with refractory vulvovaginal candidiasis with persistently positive C. albicans cultures,
MICs to various antifungals can be tested by using the broth microdilution method conducted in
accordance with Clinical and Laboratory Standards Institution (CLSI) criteria and breakpoints [98].
(See "Antifungal susceptibility testing".)
Probiotics There is no evidence that women with recurrent vulvovaginal candidiasis have
vaginal flora deficient in lactobacilli, and therefore we do not recommend use of probiotic lactobacilli

[11,12]. Although there is a popular belief that ingestion or vaginal administration of yogurt or other
agents containing live lactobacilli decreases the rate of candidal colonization and symptomatic
relapse, the few studies in this area have a number of methodologic flaws (eg, no control group,
short follow-up) and small numbers of subjects [99-103]. The value of administering live lactobacilli
to women with recurrent infection has been refuted in other studies [38,104] and this approach
should be considered unproven. The quality of probiotics varies worldwide; in the United States
these products are not standardized and often of poor quality. The US Food and Drug
Administration has cautioned against using probiotics with bacteria or yeast in immunocompromised
patients [105].
Gentian violet Topical gentian violet was widely used prior to the availability of the topical azole
intravaginal antifungal creams and suppositories. Use of this agent has largely been abandoned
because azole antimycotics are more effective (potent) and because it is messy and inconvenient
(eg, it permanently stains clothes). However, it is useful as a vulvar antipruritic and for occasional
refractory cases of vulvovaginal candidiasis, especially those demonstrating azole resistance [106].
The drug is applied to affected areas of the vulva and vagina daily for 10 to 14 days.
Boric acid We believe boric acid has no role in treatment of recurrent vulvovaginitis due to C.
albicans, unless azole resistance is demonstrated by in vitro tests [107]. There are no safety data
on long-term use of boric acid, which causes significant local irritation and has the potential for
toxicity (including death) if ingested by accident. A course of boric acid (600 mg intravaginal boric
acid vaginal suppositories daily for two weeks) should be considered only in cases of proven azoleresistant infection; these cases are rare.
Immunotherapy Local vaginal hypersensitivity to C. albicans has been proposed as the cause
of recurrent infection in some women [108]. Immunotherapy of candidal vaginitis for both prevention
and treatment is a therapeutic approach under investigation [109]. A prophylactic vaccine would
need to induce a host immune response against fungal virulence traits without altering
the tolerance/inflammation balance of the vaginal environment, whereas a therapeutic vaccine
indicated for women with recurrent vulvovaginal candidiasis could enhance or
rectify tolerance/inflammation imbalance in the vagina [110]. Two vaccines are in development.
Allergy to fluconazole The incidence of fluconazole allergy in women with
acute Candida vaginitis is unknown, but uncommon. The author has seen patients with allergic
symptoms, varying from rash to, occasionally, angioedema. It is important to recognize that
fluconazole is one member of the azole class of drugs and it is difficult to distinguish between
patients with allergy to fluconazole alone versus those with allergy to the entire azole class.
Therefore, other oral azoles such asketoconazole (Nizoral) or itraconazole (Sporanox) should not
be prescribed to patients with true fluconazole allergy. However, patients with fluconazole allergy
can receive topical azoles, such as miconazole or clotrimazole. For those patients with fluconazole
allergy manifested by angioedema or severe rash, the author has resorted to use of topical agents
instead of weekly fluconazole 150 mg. Both miconazole and clotrimazole can be prescribed on a
once weekly high dose regimen, 500 to 1500 mg, depending on the dose commercially available
locally. Other options include nystatin per vagina 100,000 units daily for 7 days for acute vaginitis or
boric acid per vagina for 7 days. Discussion with an allergist is recommended. There are no data on
the efficacy of fluconazole desensitization, which is theoretically possible.

Treatment of partners Although sexual transmission of Candida species can occur, most
experts do not recommend treatment of sexual partners since sexual activity is not a significant
cause of infection or reinfection. Although the bulk of evidence from randomized trials
does not support treatment of sexual partners [47-50], in woman with recurrent vulvovaginitis, this
issue remains controversial.
Treatment of symptomatic men is reviewed separately. (See "Balanitis and balanoposthitis in
adults".)
Breastfeeding women Nystatin does not enter breast milk and is compatible with
breastfeeding. Fluconazole is excreted in human milk, but the American Academy of Pediatrics
(AAP) considers the use of fluconazole compatible with breastfeeding [111], as no adverse effects
have been reported in breastfed infants or infants treated with parenteral fluconazole [112]. There is
no information on the effect of miconazole, butoconazole, clotrimazole, tioconazole,
or terconazole on nursing infants, but systemic absorption after maternal vaginal administration is
minimal, hence topical use in nursing mothers is reasonable.
Postcoital hypersensitivity reaction in male partner In a variant syndrome, male partners of
women with vaginal Candida colonization develop immediate postcoital itching and burning with
redness and a rash of the penis. This postcoital syndrome probably represents an acute
hypersensitivity reaction to Candida organisms or antigens in the partner's vagina, even in the
absence of symptomatic vulvovaginitis.
Males with recurrent postcoital symptoms do not benefit from topical antimycotic therapy since the
key to eradicating symptoms lies in eliminating Candida organisms from the lower genital tract of
the female sexual partner. This often requires the female partner to follow a long-term maintenance
antimycotic regimen.
A postcoital shower and application of a topical low potency corticosteroid to the penis may provide
symptomatic relief within 12 to 24 hours. Penile cultures may remain positive for Candida despite
normal physical findings.
PREVENTION As discussed above, oral nystatin does not prevent vaginal candidiasis
and lactobacillus (oral or vaginal) does not prevent postantibiotic vulvovaginitis. In women
susceptible to symptomatic yeast infections when taking antibiotic therapy, a dose
of fluconazole (150 mg orally) at the start and end of antibiotic therapy may prevent postantibiotic
vulvovaginitis [8].
COMPLEMENTARY AND ALTERNATIVE MEDICINE There is no evidence from randomized
trials that garlic, tea tree oil, yogurt (or other products containing liveLactobacillus species), or
douching is effective for treatment or prevention of vulvovaginal candidiasis due
to Candida albicans [113].
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 10 th 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.)
Basics topics (see "Patient information: Vulvovaginal yeast infection (The
Basics)" and "Patient information: Vulvar itching (The Basics)")
Beyond the Basics topics (see "Patient information: Vaginal yeast infection (Beyond the
Basics)")
SUMMARY AND RECOMMENDATIONS
Candida is considered part of the normal vaginal flora, but overgrowth of the organism and
penetration of superficial epithelial cells can result in vulvovaginitis.Candida albicans accounts
for 80 to 92 percent of episodes of vulvovaginal candidiasis; Candida glabrata is the next most
common species. (See 'Prevalence'above and 'Microbiology' above
and 'Pathogenesis' above.)
Vulvar pruritus is the dominant symptom. Vulvar burning, soreness, and irritation are
common and may result in dysuria and dyspareunia. The vulva and vagina appear
erythematous, and vulvar excoriation and fissures may be present. There is often little or no
discharge; when present, it is classically white, thick, adherent, and clumpy (curd-like or
cottage cheese-like) with no or minimal odor. (See 'Clinical features' above.)
The diagnosis of vulvovaginal candidiasis is based on the presence of Candida on wet
mount, Grams stain, or culture of vaginal discharge in a woman with characteristic clinical
findings. (See 'Office diagnosis' above.)
Culture is not necessary for diagnosis if microscopy shows yeast, but should be obtained in
(see 'Role of culture' above):
Women with clinical features of vulvovaginal candidiasis, normal vaginal pH, and
negative microscopy.
Women with persistent or recurrent symptoms because many of these women have
non-albicans infection resistant to azoles.
Treatment
Treatment is indicated to relieve symptoms. Asymptomatic women and sexual partners do
not require treatment. (See 'Treatment' above and 'Treatment of partners' above.)
The treatment regimen is based on whether the woman has an uncomplicated infection (90
percent of patients) or complicated infection (10 percent of patients). Criteria are listed in the
table (table 2). (See 'Treatment' above.)
Uncomplicated infections Oral and topical antimycotic drugs achieve comparable clinical cure
rates, which are in excess of 80 percent in uncomplicated infection (table 3). (See 'Uncomplicated
infection' above.)
We suggest a single dose of oral fluconazole (150 mg) for treatment of uncomplicated
infections rather than multidose and topical regimens (Grade 2C). (See'Uncomplicated
infection' above.)

Complicated infections Women with complicated infection require longer courses of therapy
than women with uncomplicated infection. (See 'Complicated infections' above.)
For women with severe symptoms, we suggest fluconazole (150 mg) in two sequential doses
given three days apart rather than topical antimycotic agents (Grade 2C). (See 'Severe
symptoms or compromised host' above.)
For treatment of C. glabrata, we suggest intravaginal boric acid (600 mg capsule once daily
at night for two weeks) rather than an azole, boric acid, or flucytosinecream (Grade 2C).
(See 'C. glabrata' above.)
For pregnant women, we suggest a topical imidazole (clotrimazole, miconazole) vaginally for
seven days rather than a nystatin pessary or an oral azole (Grade 2C). Case reports have
described a pattern of birth defects (abnormalities of cranium, face, bones, and heart) after
first trimester exposure to high dose oral azole therapy (400 to 800 mg/day).
(See 'Pregnancy' above.)
For women with recurrent vulvovaginitis (4 episodes/year), we suggest suppressive
maintenance therapy rather than treatment of individual episodes (Grade 2B). We prescribe
initial induction therapy with fluconazole 150 mg every 72 hours for three doses, then
maintenance fluconazole 150 mg once per week for six months. Women with recurrent
infection should try to eliminate or reduce risk factors for infection. (See 'Recurrent
infection' above.)