Obstet Gynecol Clin N Am

30 (2003) 671 684

Vulvovaginal candidiasis
Paul Nyirjesy, MDa,*, Jack D. Sobel, MDb
a

Department of Obstetrics and Gynecology, Drexel University College of Medicine,

Philadelphia, PA, USA
b
Division of Infectious Diseases, Department of Internal Medicine,
Wayne State University School of Medicine, 3390 John R Street, Detroit, MI 48201, USA

For any clinician involved in the health care of women, vaginitis is a commonly
encountered complaint and one of the most frequent reasons for patient visits to
obstetricians/gynecologists [1]. Of the many causes of vaginal infections, vulvovaginal candidiasis (VVC) is believed to be one of the most common causes, and it
has a significant impact on health care costs. Over-the-counter (OTC) sales of
antifungal vaginal medications were reported to be approximately $269 million in
1995 [2] and are estimated to have increased significantly since then. Using a
random digit-dialing survey of 2000 women representative of the United States
population, Foxman et al [2] found that 6.5% of women aged 18 or older reported at
least one presumed episode of VVC in the previous 2 months. They concluded that
55.7% of women will experience at least one symptomatic episode of VVC in their
lifetime, and this cumulative probablility seems to be higher for African-American
women than for other women. Taking into account the associated costs of VVC,
such as medical and treatment expenses, travel costs, and time missed from work,
they estimated that the total annual costs for VVC in the United States in 1995 was
$1.8 billion. VVC is a common problem with significant social costs.
VVC is best defined as the spectrum of patients who harbor Candida organisms
in their vaginas [3]. If one views VVC as a continuum, different women with VVC
will fall in different points. Some women with VVC are completely asymptomatic,
whereas others may develop frequent or severe symptoms. Certain patients may
develop primarily vulvar instead of vaginal manifestations of VVC. In recognition
of the broad range of VVC, it was proposed in 1998 that VVC be classified into
uncomplicated or complicated disease (Box 1). It has been estimated that 80% to
90% of women with VVC have uncomplicated VVC. This classification system
has important therapeutic implications, because women with complicated VVC
seem to be less likely to respond to standard short courses of antifungal therapy.

* Corresponding author. 245 N. 15th Street, 16th Floor, New College Building, Philadelphia,
PA, 19102.
E-mail address: pnyirjesy@comcast.net (P. Nyirjesy).
0889-8545/03/$ see front matter D 2003 Elsevier Inc. All rights reserved.
doi:10.1016/S0889-8545(03)00083-4

672

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

Box 1. Classification of vulvovaginal candidiasis

Uncomplicated VVC (all of the listed criteria)
Sporadic or infrequent symptomatic episodes
Mild to moderate symptoms
Candida albicans infection
Normal, nonpregnant woman
Complicated VVC (any of the listed criteria)
Recurrent episodes ( 4 episodes per year)
Severe symptoms or findings
Non-albicans yeast species
Abnormal host (eg, diabetes, immunosuppression)
From Sobel JD, Faro, S, Force RW, Foxman B, Ledger WJ, Nyirjesy
P, et al. Vulvovaginal candidiasis: epidemiologic, diagnostic,
and therapeutic considerations. Am J Obstet Gynecol 1998;178:
203 11; with permission.

Multiple prospective studies have validated the relevance of this classification

system to predicting the outcome with treatment. For example, in a study that
compared a week of topical clotrimazole cream to a single dose of oral fluconazole,
patients with severe VVC were less likely to respond to either agent [4]. In another
study that compared one versus two doses of fluconazole in women with severe or
recurrent VVC (RVVC), women with an infection caused by non-albicans
Candida sp and women with an underlying medical disease, such as diabetes,
were much more likely to fail either therapy [5]. When discussing VVC, one must
recognize that symptoms are a function of the infectious microorganism and the
host response and that not all yeast infections are the same.

Microbiology
Numerous studies suggest that C albicans is responsible for most symptomatic
episodes of VVC [3]. Because vaginal yeast cultures are not routinely obtained in
the management of uncomplicated VVC, it is difficult to assess whether the
microbiology of VVC is changing as antifungal therapy and self-treatment in
particular become more common. In specialized centers that treat women with
complicated VVC, a broad variety of non-albicans species of Candida are
encountered and may account for up to 30% of complicated VVC cases (Box 2)
[5,6]. Studies from specialized centers are hampered by the referral bias of their
patient populations and possible regional differences, however. Even in women
with RVVC, more than 90% of infections may be secondary to C albicans [7]. Of
the non-albicans yeast species implicated as causes of VVC, Candida glabrata is
the most common [5 7].

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

673

Box 2. Microbiology of vulvovaginal candidiasis

C albicans ( 90% of cases)
C glabarata
Candida parapsilosis
Candida krusei
Candida lusitaniae
Candida tropicalis
Saccharomyces cerevisiae

Epidemiology and pathogenesis

Because VVC is not a reportable disease and because there are no active
surveillance studies in the United States, prevalence estimates have relied mainly
on self-reported history of physician diagnosis. This history, in turn, may be
hampered by several different factors: recall bias, accuracy of diagnosis, patient
selection, referral bias, and confounding effects of widespread use of OTC
antifungal agents. Epidemiologic data suggest that by age 25, half of all college
women will experience at least one physician-diagnosed episode of VVC [8]. Age
seems to be an important risk factor in the incidence of VVC, with an increase in the
second decade of life and with the initiation of sexual activity [9]. Among college
women, VVC seems to be more common among African-American women than
white women [9]. Although most clinicians consider VVC more common in
pregnancy, little published information supports this view. RVVC, defined as four
or more attacks of symptomatic Candida vaginitis in the previous 12 months, may
occur in as many as 8% of women of reproductive age [10].
With complicated and uncomplicated VVC, two elements are important in the
development of a symptomatic episode. The first consists of vaginal colonization
by Candida sp, followed by the transformation from the asymptomatic state to a
symptomatic infection. There are distinct factors for colonization and transformation. Candida enters the vagina through any of a number of different sources,
including local spread from the perineum and gastrointestinal tract, digital
introduction, sexual transmission, and orogenital sex. Estrogen is believed to be
crucial in the maintenance of colonization. Whatever the mechanism of entry,
colonization seems to be a relatively common event. In one study that followed
HIV-positive and HIV-negative women over 7 years, more than 80% of HIVnegative women had at least one positive culture for Candida [11]. Vaginal
colonization as measured by culture techniques is frequently intermittent. Longterm typing studies suggest that colonization, once it occurs, may be caused by
persistence of a single strain of Candida in many women with recurrent VVC
(RVVC), although new strains of C albicans or other species of yeast also may be
introduced [12].
Epidemiologic studies and anecdotal experience suggest that various factors,
listed in Box 3, may be important in the development of VVC and RVVC. Some

674

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

Box 3. Factors involved in symptomatic uncomplicated and

complicated vulvovaginal candidiasis
Microbial factors
Species of yeast
Resistant C albicans strains
Host factors
Medical conditions
Diabetes or other abnormality in glucose metabolism
Antibiotic use
Immunosuppression (primary or medication induced)
HIV
Systemic lupus erythematosus
Other conditions requiring corticosteroid use
Vulvar dermatoses
Behavioral
Sexual factors, especially orogenital sex
Contraception
Hormone therapy or local estrogen administration
Douching and use of feminine hygiene products
Dietary factors
Primary
Lewis antigen secretor status
Local immunologic factors
Other local defense factors

of these factors are discussed in further detail. These factors may affect
colonization, transformation to symptomatic infection, or both.
Microbial factors
Even in women with complicated VVC, more than 90% of cases are caused by
C albicans [7]. Most of these strains are susceptible to available antimycotic agents,
and true resistance of C albicans isolates remains rare in patients with VVC
[13,14]. It should be noted, however, that current azole therapy is fungistatic. In
women with RVVC, it is believed that small numbers of Candida may persist in the
vagina, even during therapy, and later provide a reservoir for relapsing infection by

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

675

the same identical organism [12]. In contrast, non-albicans Candida sp demonstrate variable, often reduced, susceptibility to specific azole agents. The presence
of C glabrata, the second leading cause of VVC, is associated with a much lower
response to standard antimycotic therapy [5].
Diabetes mellitus and glucose metabolism
Patients with diabetes are less likely to respond to antimycotic therapy [5], and
they may be more prone to developing infections caused by C glabrata [15].
Anecdotally, patients occasionally report that an excess of refined sugars seems to
trigger a symptomatic episode of VVC, but few data have supported this clinical
observation. A recent finding that women with RVVC exhibited an impaired
tolerance for glucose despite having a similar incidence of overt or preclinical
diabetes than controls suggests that glucose metabolism sometimes may play a role
in the development of symptomatic Candida vaginitis [16], although the role of a
low carbohydrate diet in managing VVC remains controversial.
Antibiotic use
Recent antibiotic use is frequently reported by some women as a predictable
precipitating factor for isolated and recurrent VVC [17]. The presumed mechanism
is an antibiotic-induced decrease in lactobacilli, which facilitates an overgrowth
with Candida. The inability to find an association between an absence of vaginal
lactobacilli and VVC raises the possibility that other mechanisms may be at play,
however [18].
Estrogen
Endogenous and exogenous estrogens are believed to play a role in the
pathogenesis of VVC. Epidemiologically, VVC is rare in premenarchal females,
and it decreases in frequency in postmenopausal women. Oral contraceptives have
been suspected of contributing to RVVC, but epidemiologic data are conflicting,
and their causal role is still controversial [19]. Estrogen therapy may contribute to
RVVC in postmenopausal women by prolonging the at-risk period in women who
are prone to RVVC premenopausally. Anecdotally, the authors have noticed that
the risk of getting VVC seems increased in postmenopausal women who receive
topical estrogen, particularly when in conjunction with antibiotics. Occasionally,
tamoxifen or other estrogen agonists also may contribute to the development of
RVVC in postmenopausal women [20].
Immunosuppression
In a small number of women, RVVC may be the result of systemic immunodeficiency caused by either illness or systemic therapy with corticosteroids or
similar drugs. In HIV-infected women, vaginal colonization with Candida is
substantially increased, but the frequency of RVVC is only modestly increased,

676

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

with attack rates of VVC significantly lower than oropharyngeal candidiasis [11].
In clinical practice, immunosuppression seems to be a rare cause of VVC, and an
evaluation for an underlying illness is only indicated if other elements in the
patients history or examination suggest a need for it.
Behavioral factors
Various behavioral factors have been proposed as a cause of VVC and RVVC.
Sexual factors, particularly orogenital sex [9], may contribute to the introduction of
microorganisms from the partners mouth or saliva or may facilitate symptomatic
disease because of microtrauma to the vulva and the vestibule. Although sexual
intercourse alone may not be associated with increased Candida colonization [21],
contraceptive practices may contribute to VVC; oral contraceptives [9], use of a
diaphragm and spermicide [21], and the use of an intrauterine device [22] have
been associated with an increased risk of infection. Spinillo et al have identified
douching as a risk factor in women with RVVC caused by C glabrata [23].
Primary RVVC
In approximately half of women with RVVC, no factors that contribute to the
risk of VVC may be identified. Although women with RVVC have increased
Candida colonization rates [24], it is not known whether this enhanced colonization is vagina specific or occurs elsewhere at extragenital sites, such as the
gastrointestinal tract. In some women, enhanced colonization may be explained
by genetic predispositions. For example, women who are nonsecretors of Lewis
antigens, glycoproteins that may potentially inhibit the binding of Candida to
vaginal mucosa, are associated with a greater risk of RVVC [25] African-American
women also may be at increased risk for VVC [9].
It has been postulated that a reduction in or lack of lactobacilli in the vagina may
provide an environment that is more conducive to colonization and transformation.
This hypothesis has led many women with VVC to treatments with yogurt or
lactobacillus preparations [26], but data regarding such therapy are limited to one
small study [27]. An association between lack of lactobacilli and VVC has not been
noted [18], and women with RVVC have similar numbers and types of Lactobacillus sp as controls [28].
Another mechanism at play with RVVC may pertain to an innate host
immunologic or other deficiency. In contrast to previous hypotheses, as reviewed
by Fidel and Sobel [29], current data indicate that most women with RVVC display
normal systemic cell-mediated immune responses to Candida, although local
vaginal immune responses may differ. The role of impaired or altered local vaginal
Candida-specific immune reactivity predisposing to recurrent RVVC has been
suggested [29]. One view is that depressed or reduced protective local immunoregulatory mechanisms and cytokine elaboration result in increased susceptibility
to RVVC. Another view suggests that an abnormal heightened or increased
sensitivity is induced. The finding that vaginal epithelial cells collected from

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

677

healthy women exhibit anti-Candida activity in vitro and that such activity is
reduced in cells of women with RVVC suggests that other innate host factors play a
role in preventing yeast infections [30].

Diagnosis
The clinical symptoms of VVC are nonspecific, and clinicians should keep in
mind that a broad variety of infectious and noninfectious diseases can cause a
similar array of symptoms. To obtain an accurate diagnosis, a thorough evaluation
is necessary. Patients with symptomatic VVC may complain of vulvovaginal
itching, irritation, soreness, or burning. Traditionally, clinicians have thought of
candidiasis as a vaginal problem, but the term vulvovaginal candidiasis highlights the fact that VVC represents a spectrum of vulvar and vaginal complaints and
that many women exhibit only vulvar symptoms and signs. Although most women
commonly think of VVC as a cause of an abnormal thick, white, cheesy discharge,
many symptomatic women do not notice any change in their vaginal secretions. If it
is associated with significant vestibular or vulvar inflammation, VVC also may
cause dysuria because of the burning that occurs when urine hits the inflamed
vulvar tissues. During symptomatic episodes, many women with VVC complain of
dyspareunia. The physical examination of a patient should begin with an inspection
of the vulva, looking for signs of erythema, edema, or skin fissures. In the authors
experience, VVC is a frequent yet overlooked cause of acute vulvar and labial
erythema and edema. After insertion of the speculum, the vagina should be
inspected for the presence of vaginal thrush and other signs of VVC, such as
erythema or erosions.
In women who complain of vaginal symptoms, the standard tests that should be
performed consist of a vaginal pH measurement, saline, and 10% potassium
hydroxide microscopy. Although the vaginal pH is generally not affected by
VVC and remains less than 4.5 in premenopausal women, the finding of a normal
pH helps to exclude bacterial vaginosis, trichomoniasis, atrophic vaginitis, or some
sort of mixed infection. With saline microscopy, the examiner should look closely
for either blastospores or pseudohyphae. The background vaginal flora may
otherwise appear normal or somewhat decreased, and white blood cells are most
often noticeably absent. Because it lyses vaginal epithelial cells, the addition of
10% potassium hydroxide solution to the patients specimens may make it easier to
visualize fungal elements.
Microscopy is the mainstay in the diagnosis of VVC; however, studies show that
in academic settings, microscopy has a sensitivity of 50% at best and misses a
substantial percentage of cases in women with symptomatic VVC [6,31].
C glabrata, the second leading cause of VVC, only produces blastospores, which
may be more difficult to recognize by microscopy. Over the past few years, it also
has become increasingly recognized that microscopy also may result in falsepositive results. In a study of 61 women who were diagnosed as having VVC on the
basis of clinical examination and microscopy in a university-based outpatient

678

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

gynecology clinic, Ledger et al [32] found that 49% had a negative yeast culture
and yeast polymerase chain reaction result. Given significant rates of false-positive
and false-negative results with the standard clinical evaluation, clinicians always
should be prepared to obtain a vaginal yeast culture in women with a compatible
clinical syndrome and normal pH in whom the diagnosis cannot be definitively
established with microscopy. Culturing for yeast is particularly useful in women
with complicated VVC, because information about the type of species causing the
infection may help to influence the choice of antimycotic therapy.

Misdiagnosis
Over the past decade, the trend has been for women to rely increasingly on selfdiagnosis and self-treatment of VVC. When topical antimycotic agents were
approved for OTC use, the basic assumption was that women with a prior episode
of VVC were relatively accurate with self-diagnosis. Chaponis et al [33] found that
in 100 women with a prior episode of diagnosed VVC, 82% could accurately
recognize VVC. The perceived benefits of OTC antifungal agents include
convenience, the ability to initiate antimycotic therapy rapidly, empowerment of
women, and the potential to reduce health care costs. With the availability of OTC
antifungal agents, Lipsky et al [34] estimated a decrease in direct and indirect health
care costs of $63.75 million from 1990 to 1994.
Later studies of other patient populations have suggested that the accuracy
of self-diagnosis is poorer than previously suggested, however. In a study
of 601 women recruited from various medical and community sites in Augusta,
Georgia, Ferris et al [35] found that only 11% of women with no diagnosis and
34.5% of women with a prior diagnosis of VVC could recognize accurately the
classic scenario for candidiasis. Both groups were particularly poor at recognizing
bacterial vaginosis, with an accuracy of 3.2% and 4.4%, respectively. In 105 women
with chronic vaginal symptoms, Nyirjesy et al [26] noted that 73% of their patients
had self-treated for VVC, whereas only 28% had VVC at the time of their
evaluation. In an effort to evaluate further what proportion of symptomatic women
who purchased OTC antifungal products actually had VVC, a prospective
multicenter study found that only 34% had pure VVC and another 20% had
VVC with either bacterial vaginosis or trichomoniasis [36]. It is notable that only
95 women were enrolled in this study and that patient recruitment was described as
extremely difficult. Although self-diagnosis and self-treatment may be inaccurate in many women, it is clear that most women are eager to avoid an office
evaluation for vaginitis and are more than happy to self-treat. Misdiagnosis
potentially could end up increasing health care costs for individuals who do not
have VVC, however, and a delay in treatment could have an adverse impact if the
patient is using an antifungal agent for the wrong problem (eg, pelvic inflammatory
disease or a urinary tract infection).
As many clinicians recognize, vaginitis is frequently managed through a
telephone consultation. Telephone diagnosis offers many of the advantages of

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

679

self-diagnosis, with the added benefit that patients receive validation by a clinician
that they do have VVC. Allen-Davis et al [37] sought to evaluate the accuracy of
telephone diagnosis in a Denver-based study. A total of 485 women underwent a
prospective structured telephone nurse interview and were diagnosed over the
phone. All of the women were offered an evaluation to corroborate their diagnosis.
Of the 253 women who completed the study protocol, there was poor agreement
between the telephone diagnosis and the actual diagnosis. Poor agreement also was
noted between practitioners and the actual diagnosis, although the data did not
show whether this outcome was caused by false-negative results, which could be
attributed to the well-recognized limitations of standard office tests, or falsepositive results.
Finally, one also should recognize that optimal diagnostic techniques are
frequently not used in clinical practice. In a review of 52 medical records of
patients referred to a tertiary care center because of chronic vulvovaginal complaints, Wiesenfeld and Macio [38] noted that 42% of the referring physicians did
not perform microscopy as part of any evaluation of vaginitis and that vaginal pH
tests were performed at only 3% of office visits. Because many women with VVC
may be misdiagnosed, it is clear that one should use a culture to corroborate firmly
the diagnosis in women with complicated VVC.

Treatment
For patients with uncomplicated VVC, various therapies are available for
treatment (Table 1). The mainstays of current therapy are azole agents, which are

Table 1
Therapy for vulvovaginal candidiasis
Drug

Formulation

Dose

Nystatin
Butoconazole

100,000 U vaginal tablet

2% sustained release cream
2% cream
1% cream
2% cream
100 mg vaginal suppository
200 mg vaginal suppository
500 mg vaginal suppository
2% cream
100 mg vaginal suppository
200 mg vaginal suppository
1200 mg vaginal suppository
0.4% cream
0.8% cream
80 mg vaginal suppository
2% cream
6.5% cream
150 mg oral tablet

100,000 U/14 d
5 g/1 d
5 g/7 d
5 g/7 d
5 g/3 d
100 mg/7 d
200 mg/3 d
500 mg/1 d
5 g/7 d
100 mg/7 d
200 mg/3 d
1200 mg/1 d
5 g/7 d
5 g/3 d
80 mg/3 d
5 g/3 d
5 g/1 d
150 mg/1 d

Clotrimazole

Miconazole

Terconazole

Tioconazole
Fluconazole

680

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

available in various formulations (eg, creams, suppositories, tablets) and can be

administered either topically or orally. All azoles function through a similar
mechanism of action: inhibition of cell wall metabolism. Azoles are all fungistatic
agents. Other antifungal agents, such as topical boric acid, flucytosine, and
gentian violet, may play a more important role in the management of complicated VVC.
In terms of therapeutic efficacymost commonly defined as clinical cure
(resolution of signs and symptoms) and mycologic cure (negative follow-up
fungal culture)in women with uncomplicated VVC, cure rates of 80% to 90%
can be expected with all the agents listed in Table 1 [4]. With topical therapy, the
main side effect is localized burning in 5% to 10% of patients as a result of an
allergic or irritant reaction; some patients may object to the inherent messy nature
of a cream or suppository. Oral therapy with a single dose of fluconazole has been
shown to be as effective as a 7-day course of clotrimazole [4] and a 3-day course of
topical terconazole [39]. Systemic side effects, such as gastrointestinal intolerance,
headache, and rash, are mild, infrequent, and self-limited. Although first-trimester
exposure to single-dose fluconazole has not yet been associated with adverse
effects on pregnancy [40], fluconazole is a category C drug in pregnancy; most
clinicians tend to treat patients with topical therapy during pregnancy to limit the
amount of drug exposure. Overall, the success rate with the treatment of uncomplicated VVC is so high that lack of response often implies an incorrect initial
diagnosis. Persistent symptoms mandate re-evaluation, which should include a
vaginal yeast culture.
Given the multitude of treatment options and competing claims by various
manufacturers, it may be difficult for a clinician to select the appropriate agent for a
particular patient. Health care providers have the opportunity to tailor the therapy to
the individual patients desires. Short courses of therapy are highly effective, and
the route of therapy should be dictated by patient, not physician, preference. In
terms of patient preference, several surveys have shown that most, but not all,
women would rather use oral therapy [39,41]. If other factors are equal, asking the
individual patient which route she prefers easily identifies her choice. Other factors
to consider in the uncomplicated patient include compliance, cost, ability to insert
vaginal preparations, history of response or adverse reactions to prior treatments,
and duration of therapy.
Severe vulvovaginal candidiasis
In most studies of VVC, the severity of the infection was not specifically
addressed as a predictor of outcome. Patients with severe episodes of symptomatic
VVC are less likely to respond to standard antifungal therapy regimens, however
[4,5]. In a prospective study, 556 women with severe or recurrent VVC were
randomly assigned to either a single-dose or two-dose (every 3 days) regimen of
oral fluconazole (150 mg). The two-dose treatment group had significantly higher
clinical cure rates on day 14 (94% versus 85%) and day 35 (80% versus 67%) [5].
In patients with severe symptoms or extensive findings, clinicians should consider

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

681

offering a longer course of therapy. In patients who prefer topical therapy, it seems
reasonable to suggest at least 7 days of topical therapy.
Recurrent vulvovaginal candidiasis
In patients with RVVC, a culture is strongly recommended to confirm the diagnosis and determine the species of the infecting organism. Most of these cultures
are positive for C albicans. In a woman with RVVC who receives a conventional
course of treatment with an antifungal agent to induce an initial mycologic cure, up
to 70% can expect recurrence with a symptomatic episode within 6 months [42].
With maintenance antifungal regimens, most patients can achieve satisfactory
alleviation or control of their symptomatic episodes. Treatment options that have
been studied and shown to be effective include ketoconazole (100 mg) orally daily
[42], clotrimazole (500 mg) suppositories weekly [43], and fluconazole (150 mg)
orally once weekly [7]. Because of liver toxicity associated with the use of
ketoconazole, the latter two agents are preferred as maintenance regimens. In
approximately 50% of women, they no longer have symptomatic relapses after
stopping a 6-month course of maintenance therapy [7]. For women who do, even
longer courses of maintenance therapy may be required to suppress their infections.
Controlled studies to date have failed to demonstrate a benefit to treating a womans
partner [44]. Other approaches, such as hormonal manipulation with depot
medroxyprogesterone, use of yogurt, desensitization to Candida antigen, and a
low carbohydrate diet, lack sufficient data to support recommendation of their use.
Non-albicans Candida infections
Although clinical and in vitro resistance to C albicans is fortunately rare, nonalbicans Candida sp are less likely to respond to azole antifungal therapy [5,45,46].
Boric acid (600 mg) administered daily in a gelatin capsule seems to be effective,
particularly for C glabrata infections [47]. Initial therapy should be for a minimum
of 14 days. In patients with RVVC, the authors recommend a maintenance regimen
of 6 to 8 weeks. Topical flucytosine for vaginal use has been described as a
treatment for resistant Candida tropicalis infections [48] and has been shown to
eradicate most C glabrata infections that fail to respond to boric acid [49]. The cost
for getting this medication compounded is extensive, however, and there are
concerns about acquisition of resistance with prolonged use. The role of combination therapy for markedly resistant infections remains unstudied.

Summary
VVC represents a spectrum of disease. Although there is a clear need for better
use of diagnostic modalities and development of better treatment alternatives,
most patients with VVC, even the complicated cases, at least have the perspective of achieving adequate control of their symptoms. Future advances, particu-

682

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

larly in the area of home diagnostics, may help to optimize use of currently available medicines.

References
[1] Kent HL. Epidemiology of vaginitis. Am J Obstet Gynecol 1991;165:1168 76.
[2] Foxman B, Barlow R, DArcy H, Gillespie B, Sobel JD. Candida vaginitis: self-reported
incidence and associated costs. Sex Transm Dis 2000;27:230 5.
[3] Sobel JD, Faro S, Force RW, Foxman B, Ledger WJ, Nyirjesy P, et al. Vulvovaginal candidiasis:
epidemiologic, diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998;178:
203 11.
[4] Sobel JD, Brooker D, Stein GE, Thomason J, Wermeling DP, Weinstein L, et al. Single oral dose
fluconazole compared with conventional topical therapy of Candida vaginitis. Am J Obstet
Gynecol 1995;172:1263 8.
[5] Sobel JD, Kapernick PS, Zervos M, Reed BD, Hooton T, Soper D, et al. Treatment of complicated
Candida vaginitis: comparison of single and sequential doses of fluconazole. Am J Obstet Gynecol
2001;185:363 9.
[6] Nyirjesy P, Seeney SM, Grody MHT, Jordan CA, Buckley HR. Chronic fungal vaginitis: the
value of cultures. Am J Obstet Gynecol 1995;173:820 3.
[7] Sobel JD, Hillier S, Smolenski L, Martens M, Danna P, Panzer H, et al. Management of recurrent
vulvovaginal candidiasis (RVVC) with maintenance suppressive weekly fluconazole: a multicenter study [abstract LB-8]. In: Programs and abstracts of the 42nd Interscience Conference of
Antimicrobial Agents and Chemotherapy. San Diego; September 27 30, 2002.
[8] Hurley R, Delouvois J. Candida vaginitis. Postgrad Med J 1979;55:645 7.
[9] Geiger AM, Foxman B. Risk factors for vulvovaginal candidiasis: a case-control study among
university students. Epidemiology 1996;7:182 7.
[10] Foxman B, Marsh JV, Gillespie B, Sobel JD. Frequency and response to vaginal symptoms
among white and African American women: results of a random digit dialing survey. J Womens
Health 1998;7(9):1167 74.
[11] Ohmit SE, Sobel JD, Schuman P, Duerr A, et al. A longitudinal study of mucosal Candida
colonization and candidiasis among HIV-seropositive and at-risk HIV-seronegative women.
J Infect Dis 2003;188:118 27.
[12] Vazquez JA, Sobel JD, Demitriou R, Vaishampayan J, Lynch M, Zervos MJ. Karyotyping of
Candida albicans isolates obtained longitudinally in women with recurrent vulvovaginal candidiasis. J Infect Dis 1994;170:1566 9.
[13] Lynch ME, Sobel JD. Comparative in vitro activity of antimycotic agents against pathogenic
vaginal yeast isolates. J Med Vet Mycol 1994;32:267 74.
[14] Sobel J, Zervos M, Reed BD, Hooton T, Soper D, Nyirjesy P, et al. Fluconazole susceptibility of
vaginal isolates obtained from women with complicated Candida vaginitis: clinical implications.
Antimicrob Agents Chemother 2003;47(1):34 8.
[15] DeLeon EM, Jacober SJ, Sobel JD, Foxman B. Prevalence and risk factors for vaginal Candida
colonization in women with type I and type II diabetes. BMC Infect Dis 2002;2:1 11.
[16] Donders GG, Prenen H, Verbeke G, Reybrouck R. Impaired tolerance for glucose in women with
recurrent vaginal candidiasis. Am J Obstet Gynecol 2002;187:989 93.
[17] Spinillo A, Capuzzo E, Acciano S, DeSantolo A, Zara F. Effect of antibiotic use on the prevalence of symptomatic vulvovaginal candidiasis. Am J Obstet Gynecol 1999;180:14 7.
[18] Hawes SE, Hillier SL, Benedetti J, Stevens CE, Koutsky LA, Wolner-Hannsen P, et al. Hydrogen
peroxide-producing lactobacilli and acquisition of vaginal infections. J Infect Dis 1996;174:
1058 63.
[19] Reed BD, Gorenflo DW, Gillespie BW, Pierson CL, Zazove P. Sexual behaviors and other risk
factors for Candida vulvovaginitis. J Womens Health Gend Based Med 2000;9:645 55.

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

683

[20] Sobel JD, Chaim W, Leaman D. Recurrent vulvovaginal candidiasis associated with long-term
tamoxifen treatment in postmenopausal women. Obstet Gynecol 1996;88:704 6.
[21] Hooten TM, Roberts PL, Stamm WE. Effect of recent sexual activity and use of diaphragm on
vaginal flora. Clin Infect Dis 1994;19:274 8.
[22] Barbone F, Austin H, Louv WC, Alexander WJ. A follow-up study of methods of contraception,
sexual activity, and rates of trichomoniasis, candidiasis, and bacterial vaginosis. Am J Obstet
Gynecol 1990;163:510 4.
[23] Spinillo A, Capuzzo E, Egbe TO, Baltaro F, Nicola S, Piazzi G. Torulopsis glabrata vaginitis.
Obstet Gynecol 1995;85:993 8.
[24] Giraldo P, von Nowaskonski A, Gomes FA, Linhares I, Neves NA, Witkin SS. Vaginal colonization by Candida in asymptomatic women with and without a history of recurrent vulvovaginal candidiasis. Obstet Gynecol 2000;95:413 6.
[25] Chaim W, Foxman B, Sobel JD. Association of recurrent vaginal candidiasis and secretory ABO
and Lewis phenotype. J Infect Dis 1997;176:828 30.
[26] Nyirjesy P, Weitz MV, Grody MHT, Lorber B. Over-the-counter and alternative medicines in the
treatment of chronic vaginal symptoms. Obstet Gynecol 1997;90:50 3.
[27] Hilton E, Isenberg HD, Alperstein P, France K, Borenstein MT. Ingestion of yogurt containing
Lactobacillus acidophilus as prophylaxis for candidal vaginitis. Ann Intern Med 1992;116:353 7.
[28] Sobel JD, Chaim W. Vaginal microbiology of women with acute recurrent vulvovaginal candidiasis. J Clin Microbiol 1996;34:2497 9.
[29] Fidel Jr PL, Sobel JD. Immunopathogenesis of recurrent vulvovaginal candidiasis. Clin Microbiol Rev 1996;9:335 48.
[30] Barousse MM, Steele C, Dunlap K, Espinosa T, Boikov D, Sobel JD, et al. Growth inhibition of
Candida albicans by human vaginal epithelial cells. J Infect Dis 2001;184:1489 93.
[31] Bergman JJ, Berg AO, Schneeweiis R, Heidrich FE. Clinical comparison of microscopic and
culture techniques in the diagnosis of Candida vaginitis. J Fam Pract 1984;18:549 52.
[32] Ledger WJ, Polaneczky MM, Yih MC, Jeremias J, Tolbert V, Witkin SS. Difficulties in the
diagnosis of Candida vaginitis. Infect Dis Clin Pract 2000;9:66 9.
[33] Chaponis RJ, Bresnick PA, Weiss RR, Edwards LD. Candida vaginitis: signs and symptoms aid
womens self-recognition. J Clin Res Drug Dev 1993;7:17 23.
[34] Lipsky MS, Waters T, Sharp LK. Impact of vaginal antifungal products on utilization of health
care services: evidence from physician visits. J Am Board Fam Pract 2000;13:178 82.
[35] Ferris DG, Dekle C, Litaker MS. Womens use of over-the-counter antifungal medications for
gynecological symptoms. J Fam Pract 1996;42:595 600.
[36] Ferris DG, Nyirjesy P, Sobel JD, Soper D, Pavletic A, Litaker MS. Over-the-counter antifungal
drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet Gynecol 2002;99:
419 25.
[37] Allen-Davis JT, Beck A, Parker R, Ellis J, Polley D. Assessment of vulvovaginal complaints:
accuracy of telephone triage and in-office diagnosis. Obstet Gynecol 2002;99:18 22.
[38] Wiesenfeld HC, Macio I. The infrequent use of office-based diagnostic tests for vaginitis. Am J
Obstet Gynecol 1999;181:39 41.
[39] Slavin MB, Benrubi GI, Parker R, Griffin CR, Magee MJ. Single dose oral fluconazole vs
intravaginal terconazole in treatment of Candida vaginitis: comparison and pilot study. J Fla
Med Assoc 1992;79:693 6.
[40] Mastroiacovo P, Mazzone T, Botto LD, Serafini MA, Finardi A, Caramelli L, et al. Prospective
assessment of pregnancy outcomes after first-trimester exposure to fluconazole. Am J Obstet
Gynecol 1996;175:1645 50.
[41] Tooley PJ. Patients and doctor preferences in the treatment of vaginal candidiasis. Practitioner
1990;71:73 6.
[42] Sobel JD. Recurrent vulvovaginal candidiasis: a prospective study of the efficacy of maintenance
ketoconazole therapy. N Engl J Med 1986;315:1455 8.
[43] Davidon F, Mould RF. Recurrent genital candidosis in women and the effect of intermittent
prophylactic treatment. Br J Vener Dis 1978;54:176 83.

684

P. Nyirjesy, J.D. Sobel / Obstet Gynecol Clin N Am 30 (2003) 671684

[44] Fong IW. The value of treating the sexual partners of women with recurrent vaginal candidiasis
with ketoconazole. Genitourin Med 1992;68:174 6.
[45] Sood G, Nyirjesy P, Weitz MV, Chatwani A. Terconazole cream for non-Candida albicans
fungal vaginitis: results of a retrospective analysis. Infect Dis Obstet Gynecol 2000;8:240 3.
[46] Singh S, Sobel JD, Bhargava P, Boikov D, Vazquez JA. Vaginitis due to Candida krusei:
epidemiology, clinical aspects, and therapy. Clin Infect Dis 2002;35:1066 70.
[47] Sobel JD, Chaim W. Treatment of Candida glabrata vaginitis: a retrospective review of boric acid
therapy. Clin Infect Dis 1997;24:649 52.
[48] Horowiz B. Topical flucytosine for chronic recurrent Candida tropicalis infections. J Reprod Med
1986;31:821 4.
[49] Sobel JD, Chaim W, Nagappan V, Leaman D. Treatment of vaginitis due to C. glabrata: use of
topical boric acid and flucytosine. Am J Obstet Gynecol, in press.