Clinical Topic A-Z Clinical Speciality

Candida - female genital

Candida - female genital
D002181Candidiasis, Vulvovaginal
Infections and infestationsSexual healthWomen's health
2012-08-01Last revised in August 2012

Candida - female genital - Summary

Vulvovaginal candidiasis is a symptomatic inflammation of the vagina and/or vulva caused by a superficial fungal infection (usually a Candida species), although other yeasts are occasionally implicated.

Candida is part of the normal vulvovaginal flora in 20–50% of asymptomatic women.

Recurrent episodes occur in 30% of women of childbearing age. About 1% of women have almost continuous symptoms.

The main risk factors are antibiotics, pregnancy, and poorly controlled diabetes.

Symptoms may include vulval itching (often the defining symptom), vulval soreness and irritation, vaginal discharge (usually non-offensive), superficial dyspareunia, and dysuria.

Signs may include vulvovaginal inflammation, erythema, vaginal fissuring, and excoriation of the vulva. Vaginal discharge is often white, 'cheese-like', and non-offensive, but may be watery or purulent.

Microscopy and fungal culture of vaginal secretions to identify yeasts is only recommended for supporting the diagnosis, and in cases of severe or recurrent vulvovaginal candidiasis, or treatment failure.

Vulvovaginal candidiasis is not a sexually transmitted infection (STI). Partners do not need to be told, tested, or treated (unless they also have genital symptoms). Screening for STIs should be arranged if the woman is concerned or at risk.

In uncomplicated infection, advice should be offered on:

Avoidance of local irritants (such as soaps and shower gels).

Use of probiotics (e.g. live yoghurts) orally or topically. Although there is no evidence that they are effective, there is no concern about adverse effects.

For treatment of vulval symptoms, a topical imidazole cream (e.g. clotrimazole) should be considered.

Treatment of uncomplicated vaginal infection involves:

A short course of an intravaginal antifungal (e.g. clotrimazole, econazole, miconazole, or fenticonazole) or oral antifungal (e.g. fluconazole or itraconazole).

Treatment of severe vaginal infection involves:

Either two doses of oral fluconazole (150 mg) 3 days apart, or, if oral treatment is contraindicated, using one clotrimazole 500 mg pessary and repeat 3 days later.

Treatment of recurrent vaginal infection involves:

A longer course of oral or topical treatment.

For future management, either 'treatment as required’ with a prescription to be used if symptoms recur, or a 6 months ‘maintenance regimen’ of an oral or intravaginal antifungal (off-label).

If the woman is pregnant:

Oral antifungals should not be used.

Intravaginal clotrimazole or miconazole for at least 7 days are the treatments of choice.

If the woman is immunocompromised:

Modifiable conditions (e.g. diabetes) should be corrected.

Treatment options are either an oral antifungal for 7 days, or intravaginal antifungals for 6–14 days.

Specialist advice should be sought or the woman referred to a specialist, if:

Treatment failure is unexplained.

Non-albicans Candida species infection is present.

Systemic symptoms occur.

The diagnosis is unclear.

Have I got the right topic?

144months3060monthsFemale

This CKS topic covers the management of vulvovaginal candidiasis (genital thrush) in women.

This CKS topic does not cover other causes of vaginal discharge and itching.

There are separate CKS topics on Bacterial vaginosis, Candida - oral, Candida - skin, Chlamydia - uncomplicated genital, Pruritus vulvae, and Trichomoniasis.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in August 2012

December 2013 — minor update. Text updated to reflect that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections [MHRA, 2013j].

August 2013 — minor update to the text to reflect recent guidance from the European Medicines Agency regarding the use of oral ketoconazole [MHRA, 2013g].

August 2012 — reviewed. A literature search was conducted in July 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. Changes to clinical recommendations have been made, including syndromic management of uncomplicated vulvovaginitis and management of non-albicans candida infection. Changes to drug regimens for the treatment of candida, including those for induction and maintenance, have been made.

Previous changes

September 2011 — minor update. The Cochrane Review Interventions for prevention and treatment of vulvovaginal candidiasis in women with HIV infection is cited regarding the treatment of immunocompromised women, and in the section on recurrent infection [Ray et al, 2011]. Issued in September 2011.

March 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

May 2010 — minor update. The manufacturer of econazole 1% cream (Pevaryl®) states that it is not recommended for use during pregnancy. Prescription removed. Issued in May 2010.

March 2010 — minor update. Results of the updated Cochrane systematic review on oral versus intra-vaginal imidazole and triazole antifungal treatment of uncomplicated vulvovaginal candidiasis have been updated in the Supporting evidence section. Issued in March 2010.

May 2009 — minor update. Econacort-1® pessaries have been discontinued so this prescription has been removed. Other intravaginal econazole preparations remain available. Issued in June 2009.

February 2009 — minor update. Nystatin intravaginal cream (Nystan®) has been discontinued, text has been updated and prescriptions removed. Issued in March 2009.

January 2009 — minor update. Gyno-Daktarin® pessaries have been discontinued, text has been updated and prescriptions removed. Issued in February 2009.

June to September 2007 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

There are no major changes to the recommendations.

April 2008 — minor update. Medicines and Healthcare products Regulatory Agency (MHRA) guidance regarding oral ketoconazole added [MHRA, 2008].

February 2008 — minor update. Late comments from the British Association for Sexual Health and HIV (BASHH) have been included. Gyno-pevaryl 1 combination pack has been discontinued, prescriptions have been removed. Issued in March 2008.

March 2004 — reviewed. Validated in May 2004 and issued in July 2004.

January 2001 — reviewed. Validated in March 2001 and issued in June 2001.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 July 2012

HTAs (Health Technology Assessments)

No new HTAs since 1 July 2012.

Economic appraisals

No new economic appraisals relevant to England since 1 July 2012.

Systematic reviews and meta-analyses

Systematic reviews published since the last revision of this topic:

Rosa, M.I., Silva, B.R., Pires, P.S., et al. (2012) Weekly fluconazole therapy for recurrent vulvovaginal candidiasis: a systematic review and meta-analysis. European Journal of Obstetrics, Gynecology, and Reproductive Biology 167(2), 132-6. [Abstract]

Primary evidence

No new randomized controlled trials published in the major journals since 1 July 2012.

Observational studies published since the last revision of this topic:

Molgaard-Nielsen, D., Pasternak, B., and Hviid, A. (2013) Use of oral fluconazole during pregnancy and the risk of birth defects. New England Journal of Medicine 369(9), 830-839.

New policies

No new national policies or guidelines since 1 July 2012.

New safety alerts

No new safety alerts since 1 July 2012.

Changes in product availability

No changes in product availability since 1 July 2012.

Goals and outcome measures

Goals

To cure the symptoms of an isolated event of vulvovaginal candidiasis

To cure the symptoms of recurrent vulvovaginal candidiasis, and to prevent or reduce further recurrence

Background information

Definition

What is it?

Vulvovaginal candidiasis

Definition of vulvovaginal candidiasis

Vulvovaginal candidiasis is a symptomatic inflammation of the vagina and/or vulva caused by a superficial fungal infection, usually a Candida species, although other yeasts are occasionally implicated.

Candida albicans accounts for 80–92% of cases.

C. glabrata is responsible for a further 5%.

C. tropicalis, C. parapsilosis, C. krusei, C. kefyr, C. guilliermondii, and Saccharomyces cerevisiae account for most of the remaining cases.

Vulvovaginal candidiasis is also known as vulvovaginal candidosis, vaginal thrush, monilial thrush, and vaginal yeast infection.

Candida is considered part of the normal vulvovaginal flora as it is found in about 20–50% of asymptomatic women.

[CDC, 2006; BASHH, 2007; FSRH, 2012]

Classification

Classification of vulvovaginal candidiasis

Vulvovaginal candidiasis may be classified as uncomplicated or complicated:

Uncomplicated vulvovaginal candidiasis is:

Sporadic or infrequent, and

Mild to moderate, and

Likely to be due to Candida albicans, and

NOT associated with risk factors such as pregnancy, poorly controlled diabetes, compromised immunity, and debilitation.

Complicated vulvovaginal candidiasis includes:

Recurrent infection — four or more documented episodes in 1 year, with at least partial resolution of symptoms between episodes.

Severe infection — extensive vulvar erythema, oedema, excoriation, and fissure formation.

Infection with yeasts other than Candida albicans.

Infection during pregnancy.

Infection in immunocompromised women — with debilitating medical conditions such as uncontrolled diabetes mellitus, or who are taking systemic corticosteroid treatment.

[CDC, 2006]

Prevalence

How common is it?

Incidence:

The lifetime incidence of vulvovaginal candidiasis is estimated to be 50–75%.

Vulvovaginal candidiasis is most likely to develop during the fertile years.

The incidence of vulvovaginal candidiasis rises rapidly after the menarche and peaks in the third and fourth decade of life. Vulvovaginal candidiasis is much less common in prepubertal girls and postmenopausal women.

Vulvovaginal candidiasis is more common during pregnancy.

During reproductive years 10-20% of women may be colonized with candida but have no clinical symptoms [BASHH, 2007].

Prevalence:

In women with an abnormal vaginal discharge, candidiasis is found to be the cause in about one in three cases [RCGP and BASHH, 2006].

The prevalence of vulvovaginal candidiasis in the general population is not known, but the infection is diagnosed in 5–15% of women who attend sexually transmitted disease clinics and family planning clinics.

Recurrent episodes are experienced by about 30% of women of childbearing age, and about 1% of women are almost continuously troubled by it (approximately 150,000 women in the UK) [HPA, 2006].

[Sobel et al, 1998; Nyirjesy and Sobel, 2003]

Complications and prognosis

Complications

Treatment failure occurs in up to 20% of women receiving antifungal treatment for uncomplicated vulvovaginal candidiasis. Treatment failure is considered to have occurred if symptoms do not resolve within 7–14 days [Sobel et al, 1998; Watson et al, 2002].

Depression and psychosexual problems may affect women who have recurrent candidiasis [Working Group of the British Society for Medical Mycology, 1995].

Candidal balanitis may occur rarely in male partners of women with vulvovaginal candidiasis [Spence, 2010]. For further information, see the CKS topic on Balanitis.

Prognosis

The natural progression of vulvovaginal candidiasis has not been well documented.

Treatment with imidazoles relieves symptoms and results in negative cultures in 80–90% of women who complete treatment [CDC, 2006]. For more information, see Supporting evidence.

Recurrent vulvovaginal candidiasis, (defined as four or more episodes in a 1-year period with at least partial resolution between episodes), occurs in approximately 5% of women of reproductive years who have had an episode of vulvovaginal candidiasis [BASHH, 2007].

Risk factors

What are the risk factors?

A number of factors have been implicated as triggers for episodes of vulvovaginal candidiasis. However, apart from antibiotics, pregnancy and poorly controlled diabetes, CKS found that the evidence to support individual risk factors is inconclusive.

Accepted risk factors for vulvovaginal candidiasis are:

Antibiotics:

Vulvovaginal candidiasis occurs in about 30% of women taking a course of systemic or intravaginal antibiotics. No antibiotic has been identified as having a low risk for vulvovaginal candidiasis [Sobel, 2007].

Only women who are already colonized with Candida are at risk of vulvovaginal candidiasis following treatment with antibiotics [Sobel, 2007].

Pregnancy:

During pregnancy, asymptomatic vaginal colonization with Candida, acute vulvovaginal candidiasis, recurrent infection, and treatment failure are all more common [Sobel, 2007].

Diabetes mellitus (poorly controlled):

Poorly controlled diabetes predisposes to symptomatic vulvovaginal candidiasis [Sobel, 2007].

Vulvovaginal candidiasis is not more frequent in women with well controlled diabetes [Sobel, 2007].

Women without diabetes who have recurrent vulvovaginal candidiasis tend to have substantially higher plasma glucose levels (but still within the normal range) [Sobel, 2007].

Immunocompromised status, such as HIV/AIDS:

Vaginal colonization and vulvovaginal candidiasis are more common in women with HIV/AIDS. The risk increases with, longer time since diagnosis, lower CD4 count, and higher HIV viral load [Duerr et al, 2003; Ohmit et al, 2003].

In women with HIV/AIDS, oral candidiasis is more likely to be a problem than vulvovaginal candidiasis [Ohmit et al, 2003].

Although vulvovaginal candidiasis is more common among HIV-infected women, it is no more severe in this group than in women without HIV [Duerr et al, 2003].

Possible risk factors for vulvovaginal candidiasis:

Contraceptives:

It is a commonly held view that contraceptives, especially combined oral contraceptives, increase the risk of vulvovaginal candidiasis. There are many studies of the various contraceptive methods, but all have methodological weaknesses and the results are inconsistent [Sobel, 2007].

Sexual behaviours:

Although the incidence of vulvovaginal candidiasis increases greatly during the years of peak sexual activity, CKS found only weak evidence that sexual behaviours influence transmission, and no good evidence of benefit from treating sexual partners.

Women receiving oral sex may be at greater risk of vulvovaginal candidiasis [Mardh et al, 2002; Sobel, 2007].

Treatment of asymptomatic male sexual partners is not advocated by guidelines (such as [CDC, 2006; FSRH, 2012]) as there is little evidence of benefit.

Unlikely risk factors for vulvovaginal candidiasis:

Local irritants

CKS found no evidence that local irritants such as soaps and shower gels increase the risk of vulvovaginal candidiasis.

Tight-fitting clothing

There is no evidence to suggest that tight-fitting clothing or non-cotton underwear is a risk factor for vulvovaginal candidiasis [Sobel, 2007].

Female hygiene and sanitation:

Sanitary towels, tampons and panty liners: when used appropriately, vulvovaginal candidiasis does not appear to be associated with tampons, sanitary towels or panty liners [FSRH, 2012].

Vaginal douching: CKS found no evidence that douching increases the likelihood of vulvovaginal candidiasis [Mardh et al, 2002].

Diagnosis and assessment

Diagnosis and assessment of female genital candida

Assessment

How do I assess a woman with vulvovaginal candidiasis?

Assess symptoms to ensure they are consistent with vulvovaginal candidiasis.

Enquire about any previous episodes. Is this an isolated episode, a recurrence, or treatment failure?

Ask about any treatments that have been tried already (over-the-counter or prescribed).

Assess severity — in severe inflammation there is extensive vulvar erythema, oedema, excoriation, and fissure formation.

Enquire into the presence of risk factors for vulvovaginal candidiasis, such as recent use of antibiotics, pregnancy, diabetes mellitus, and immunocompromised status.

Consider testing for risk factors.

Testing for risk factors

Testing for risk factors

Diabetes mellitus:

Screen the urine for glucose in women with recurrent or complicated vulvovaginal candidiasis.

Consider a fasting glucose test for postmenopausal women and for women with symptoms suggestive of diabetes mellitus. For more information see the CKS topic on Diabetes - type 2.

HIV:

Although routine testing for HIV is not recommended in women with vulvovaginal candidiasis (uncomplicated, complicated, or recurrent) who do not appear to be at risk of sexually transmitted disease, it is important to test for HIV if the woman wishes to be tested, or if there are features suggestive of immunosuppression and/or if the person is at high risk for HIV.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion in guidelines [BASHH, 2006; CDC, 2006; RCGP and BASHH, 2006; BASHH, 2007].

Risk factors

The evidence on risk factors is summarized in the section Risk factors.

These recommendations are mainly based on expert opinion because CKS found no relevant clinical trials.

Diabetes mellitus

Guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings recommend considering potential triggers such as diabetes mellitus in women with recurrent vulvovaginal candidiasis [FSRH, 2012].

An American expert has recommended doing a glucose-tolerance test for postmenopausal women because they rarely have vulvovaginal candidiasis without an underlying risk factor. The risk (prior probability) of diabetes in this group was not estimated [Sobel, 2003; Sobel, 2007].

CKS therefore recommends testing the urine for glucose in women with severe or recurrent vulvovaginal candidiasis, and considering a glucose-tolerance test for postmenopausal women with vulvovaginal candidiasis.

HIV

One expert recommends that only women with recurrent vulvovaginal candidosis who have risk factors for HIV infection should be tested for HIV [Sobel, 2007]. The reasoning is that:

Up to 8% of women who are HIV negative have recurrent vulvovaginal candidosis.

Most women who have vulvovaginal candidosis are HIV negative.

The benefits of screening women in this group for HIV are doubtful and have not been studied.

One study of women with HIV/AIDS found that oral candidiasis was more frequent than vulvovaginal candidiasis [Ohmit et al, 2003].

Vulvovaginal candidiasis is no more severe in women with HIV than those without [Duerr et al, 2003].

CKS therefore recommends that otherwise healthy women who do not appear to be at risk from sexually transmitted disease should not be tested for HIV unless the woman requests a test. If there are other features suggestive of immunosuppression however, and/or if the person is at high risk for HIV then the person should be offered HIV testing.

Symptoms

What are the symptoms of vulvovaginal candidiasis?

Symptoms include:

Vulval itching — often the defining symptom.

Vulval soreness and irritation.

Vaginal discharge — not always present, usually non-malodorous.

Superficial dyspareunia.

Dysuria (pain or discomfort during urination) may be present.

Basis for recommendation

Basis for recommendation

This information is based on expert opinion in literature reviews and guidelines [Anderson et al, 2004; CDC, 2006; RCGP and BASHH, 2006; BASHH, 2007; FSRH, 2012].

Signs

What are the signs of vulvovaginal candidiasis?

An examination is not always necessary if the history indicates acute uncomplicated vulvovaginal candidiasis, the risk of a sexually transmitted infection is low, and there are no symptoms suggestive of an upper genital tract infection.

Signs include:

Vulvovaginal inflammation (not always present):

Erythema — usually localized to the vagina and vulva, but may extend to the labia majora and perineum.

Vaginal fissuring and/or oedema.

Excoriation of the vulva.

Satellite lesions (rare; may indicate other fungal conditions or herpes simplex virus).

Vaginal discharge, sometimes white, 'cheese-like' and non-offensive, but may be watery or purulent.

None of these signs are pathognomic of vulvovaginal candidiasis.

Basis for recommendation

Basis for recommendation

This information is based on expert opinion in literature reviews and guidelines [Anderson et al, 2004; CDC, 2006; RCGP and BASHH, 2006; BASHH, 2011; FSRH, 2012].

Examination not always necessary

This recommendation is based on expert advice in guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012], and also expert opinion in the guideline Sexually transmitted infections in Primary Care published jointly by the Royal College of General Practitioners Sex, Drugs and HIV Task Group and the British Association for Sexual Health and HIV [RCGP and BASHH, 2006]. Expert opinion in these guidelines does not recommend routinely examining a woman whose history suggests acute uncomplicated vulvovaginal candidiasis but recommends a syndromic approach.

Investigations

What investigations should I undertake?

No investigations are necessary if the history indicates acute uncomplicated vulvovaginal candidiasis, the risk of a sexually transmitted infection is low, and there are no symptoms suggestive of an upper genital tract infection.

Measuring vaginal pH is recommended if the woman is examined.

A high vaginal swab (HVS) is recommended for

Supporting the diagnosis when this is uncertain such as when symptoms, signs and/or pH are inconsistent with a diagnosis.

Pregnancy, postpartum, post-abortion, or post-instrumentation.

Treatment failure.

Recurrent vulvovaginal candidiasis.

Speciated fungal culture of vaginal secretions to identify yeasts is recommended for recurrent infection.

Consider additional tests such as full blood count and random blood glucose if there is recurrent vulvovaginal candidiasis, depending on clinical judgement.

Additional information

Point-of-care test: pH of vaginal fluid:

This test may be used if the woman is being examined.

Secretions should be collected from the lateral sides of the vaginal wall using a swab [FSRH, 2012].

Vaginal pH testing can be used to give an indication of the local vaginal ecology. If the woman has vulvovaginal candidiasis, the pH is usually equal to or below 4.5, and if the woman has bacterial vaginosis or trichomoniasis vaginalis, then the pH is usually above 4.5.

High vaginal swab

Take a high vaginal swab (HVS) from the lateral sides of the vaginal wall [FSRH, 2012].

If an examination is not considered necessary, or if it is not easy to take a swab, a blind or self-taken swab is an alternative option [BASHH, 2006], especially if recurrent or persistent vulvovaginal candidiasis is suspected.

Speciated culture of vaginal secretions to identify the species type:

Request 'fungal speciation' to non-albicans Candida species' if/when treatment fails. Although microscopy and culture confirms the presence/absence of a yeast in a specimen, many laboratories must be specifically requested to further test whether the yeast is C. albicans or not.

A high vaginal swab is directly plated on to solid fungal media in the laboratory.

Basis for recommendation

Basis for recommendation

Guidelines on strategies of testing to diagnose vulvovaginal candidiasis are largely based on expert opinion as there is little evidence on their clinical effectiveness.

Investigations not needed

A syndromic approach for women with uncomplicated vulvovaginal candidiasis is suggested in guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012], and also suggested by expert opinion in the guideline Sexually transmitted infections in Primary Care published jointly by the Royal College of General Practitioners Sex, Drugs and HIV Task Group and the British Association for Sexual Health and HIV [RCGP and BASHH, 2006].

Point of care and laboratory tests

Guidelines differ in their recommendations for point-of-care and laboratory tests for women with suspected acute uncomplicated vulvovaginal candidiasis. For example, guidelines from:

The Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings do not recommend routinely investigating vaginal secretions (pH, fungal microscopy, culture). Neither do they suggest always examining a woman if the history suggests uncomplicated candidal vulvovaginitis. However, if an examination is done, they recommend a vaginal pH test using narrow-range pH paper as the result can be used to assess the likelihood of candida. They warn that an HVS is of limited value, may under-diagnose bacterial vaginosis, and also report commensal bacteria which may lead to over-treatment and anxiety [FSRH, 2012].

The British Association for Sexual Health and HIV (BASHH) recommends fungal microscopy and culture in symptomatic women whenever possible [BASHH, 2006; BASHH, 2007]. They comment that treatment on the basis of symptoms alone leads to over-treatment in a large number of women [BASHH, 2006].

The Royal College of General Practitioners also recommends syndromic management if the infection sounds like candida [RCGP and BASHH, 2006].

The Centers for Disease Control (CDC) and Prevention recommend always testing vaginal pH and doing fungal microscopy and culture of vaginal secretions [CDC, 2006].

The Health Protection Agency recommends testing vaginal pH in all women with suspected vulvovaginal candidiasis, but microscopy and culture only in women with recurrent disease [HPA, 2011].

CKS has followed the FSRH guidelines because they most clearly distinguish the various different clinical scenarios, and reflect current practice in primary healthcare [FSRH, 2012].

CKS does not recommend routine fungal microscopy and culture in women with features typical of acute, uncomplicated vulvovaginal candidiasis because this is not practical in primary care and there is no evidence of clinical benefit.

Differential diagnosis

What conditions should I exclude in a woman with suspected vulvovaginal candidiasis?

In a woman with suspected vulvovaginal candidiasis:

Exclude common infections with similar symptoms, which may co-exist (compared in Table 1) — see the CKS topics on Bacterial vaginosis and Trichomoniasis.

Consider other conditions such as:

Infections (e.g. chlamydia, gonorrhoea, genital herpes, urinary tract infection).

Non-infective conditions , particularly when symptoms are chronic. For example normal physiological discharge, irritants, vulval eczema or psoriasis, lichen simplex or sclerosus, malignancies, atrophic vaginitis, foreign body, allergy (e.g. latex in condoms), mechanical irritation, vulval pain syndromes and psychosexual problems.

Table 1 . Clinical features associated with the three most common causes of vaginal discharge during the reproductive years.
Feature Bacterial vaginosis Trichomoniasis Vulvovaginal candidiasis
Symptoms
Discharge Thin discharge Scanty to profuse or frothy yellow discharge Thick white discharge
Odour Offensive or fishy odour Offensive odour Non-offensive odour
Discomfort No discomfort or itch Vulval itch or soreness Dysuria (external) Low abdominal pain Dyspareunia Vulval itch Superficial dyspareunia Dysuria
Signs
Inflammation Discharge coating vagina and vestibule No inflammation of vulva Vulvitis and vaginitis Cervicitis 'Strawberry' cervix (ectocervix resembles the surface of a strawberry) Normal appearance Vulval erythema, oedema, fissuring, satellite lesions
Point of care test
Vaginal pH Vaginal pH > 4.5 Vaginal pH > 4.5 Vaginal pH < or equal to 4.5
Adapted from: [FSRH, 2012].

Other conditions to consider

Other infective and non-infective conditions to consider

Infections causing vaginal symptoms and which may need to be differentiated from vulvovaginal candidiasis include:

Bacterial vaginosis:

The most common infection that causes abnormal vaginal discharge (diagnosed in 40–50% of premenopausal women presenting with a vaginal discharge). Itch is not usually prominent, discharge is usually white and homogeneous; and malodour is usually the most prominent feature.

Trichomoniasis:

Trichomoniasis is associated with itch and vaginal discharge, which is usually profuse, frothy, grey-green, and malodorous. It is relatively uncommon.

Chlamydia:

Chlamydia can cause vaginal discharge and dysuria, but does not usually present with itch.

Gonorrhoea:

Gonorrhoea rarely presents with itch, but is associated with pain and a purulent cervical discharge.

Genital herpes:

Genital herpes may present with redness, itch, and ulceration, although discharge is uncommon, and acute vulval pain is often the defining symptom.

Simultaneous infection:

It is possible for two or more infections to coexist, such as bacterial vaginosis and candida.

Non-infective conditions causing vaginal symptoms and which may need to be differentiated from vulvovaginal candidiasis include:

Normal physiological discharge:

Normal physiological discharge may be mistaken for candidiasis, although there should be no irritation, itch, or pain, and it should not be profuse.

Physiological discharge increases suddenly in menarchal girls, and varies throughout the menstrual cycle.

Pregnancy often causes physiological discharge.

Potential irritants:

Irritants may result in vaginal discharge, although there is little evidence concerning the possible extent of their contribution to the problem. Potential irritants include spermicides, perfumed soap or washing powders, frequent douching, or wearing tight, non-absorbent underwear (such as nylon).

Vulval eczema, psoriasis, lichen simplex or sclerosus:

These conditions may cause itch similar to that caused by vulvovaginal candidiasis.

Malignancies:

Malignancies of the vulva, vagina, cervix, or uterine lining are rare but serious causes of vaginal discharge.

Atrophic vaginitis:

Atrophic vaginitis may cause vaginal discharge in postmenopausal women, although possible malignancy should also be considered.

Foreign body:

A foreign body, such as a tampon, may result in vaginal discharge.

Allergy:

For example, allergy to chemicals or latex.

Mechanical irritation:

Due to lack of lubrication.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion in literature reviews and guidelines [Anderson et al, 2004; CDC, 2006; RCGP and BASHH, 2006; FSRH, 2012].

Assessing possible presence of STIs

When should I consider the risk that sexually transmitted infections may be present?

When appropriate:

Reassure the woman that vulvovaginal candidiasis is not a sexually transmitted infection (STI). Her partner will therefore not need to be told, tested, or treated (unless they also have genital symptoms).

Advise the woman to consider screening for STIs if she is concerned or if she has any of the following risk factors:

Age under 25 years.

New sexual partner or more than one sexual partner in last year.

Misuse of alcohol or 'recreational' drugs.

Early age of onset of sexual activity.

Sexual activity without use of condoms.

Known contact of a sexually transmitted infection.

Symptoms indicative of upper reproductive tract infection (abdominal pain, deep dyspareunia, abnormal vaginal bleeding, dysuria, pyrexia).

Basis for recommendation

Basis for recommendation

These recommendations follow guidelines published by the National Institute for Health and Care Excellence [NICE, 2007], and guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012].

Management

Management

Scenario: Uncomplicated infection : covers the management of women presenting with an uncomplicated isolated episode of vulvovaginal candidiasis, and how to manage treatment failure. Uncomplicated vulvovaginal candidiasis is defined as:

Sporadic or infrequent, and

Mild to moderate, and

Likely to be due to Candida albicans, and

NOT associated with risk factors such as pregnancy, poorly controlled diabetes, compromised immunity, and debilitation.

Scenario: Severe infection : covers the management of women presenting with severe vulvovaginal candidiasis (i.e. with extensive vulvar erythema, oedema, excoriation, and fissure formation), and how to manage treatment failure.

Scenario: Recurrent infection : covers the management of women suffering from recurrent vulvovaginal candidiasis (i.e. four or more episodes in a year).

Scenario: During pregnancy : covers the management of women who are pregnant and have vulvovaginal candidiasis, and how to manage treatment failure.

Scenario: Diabetes or immunocompromised : covers the management of vulvovaginal candidiasis in women who have poorly controlled diabetes mellitus, or who are immunocompromised.

Scenario: Uncomplicated infection

Scenario: Uncomplicated female genital candida infection

144months3060monthsFemale

Treating vulvovaginal candidiasis

How should I treat uncomplicated vulvovaginal candidiasis?

Prescribe an initial course of an intravaginal antifungal (such as clotrimazole, econazole, miconazole, or fenticonazole) or oral antifungal (such as fluconazole or itraconazole).

Intravaginal clotrimazole and oral fluconazole can be purchased over-the-counter.

For vulval symptoms, consider prescribing a topical imidazole (e.g. clotrimazole) in addition to an oral or intravaginal antifungal.

Clotrimazole is available as combination pack containing a 10% vaginal cream and a 2% topical cream (Canesten® Cream Combi) and a combination pack containing a 500 mg vaginal pessary and a 2% topical cream (Canesten® Combi).

Clotrimazole cream may also be bought over-the-counter.

Topical econazole and miconazole cream are not licensed to be applied to the vulva. However, intravaginal econazole and miconazole cream may be applied directly to the vulva to manage vulval symptoms.

Choice of route and formulation depends upon a number of factors, including the woman's preference and age.

For post-pubertal girls, consider prescribing antifungal pessaries or cream inserted high into the vagina (including during menstruation), or oral fluconazole.

For pre-pubertal girls, consider prescribing an external topical antifungal cream, and seek specialist advice if this is not effective.

Advise the woman to return if symptoms have not resolved within 7–14 days.

Follow-up and test of cure is not necessary if symptoms resolve.

Basis for recommendation

Basis for recommendation

These recommendations are based on published expert opinion from the medical literature, systematic reviews, and randomized controlled trials (RCTs) [CDC, 2006l; BASHH, 2007h; Spence, 2010; FSRH, 2012a].

Recommended treatments

These recommendations are based on expert opinion in the United Kingdom National Guideline on the management of vulvovaginal candidiasis published by the clinical effectiveness group of the British Society of Sexual Health and HIV (BASHH) [BASHH, 2007h] and on a guideline developed by the Faculty of Sexual and Reproductive Healthcare (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012a].

There is evidence that intravaginal clotrimazole, and miconazole, as well as oral itraconazole, are all effective against acute uncomplicated vulvovaginal candidiasis. Vaginal and oral azole treatments give clinical cure rates of about 75% and laboratory cure rates of about 80% for acute vulvovaginal candidiasis.

Evidence from randomized controlled trials (RCTs) shows oral triazoles (fluconazole and itraconazole) to be as effective as vaginal imidazoles for the treatment of vulvovaginal candidiasis. However, there is evidence that time to relief is shorter with topical treatments than with oral treatments.

Guidelines developed by the Faculty of Sexual and Reproductive Healthcare (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings suggest vulval application of imidazoles for symptom relief but state that they may cause irritation and that there is little evidence that they are more beneficial than emollients [FSRH, 2012a].

Pre- and post-pubertal girls

These recommendations are based on published expert opinion in the British National Formulary for Children [BNF for Children, 2012].

Oral fluconazole is not licensed for use in children less than 16 years old for the treatment of vaginal candidiasis [ABPI Medicines Compendium, 2012fp]. However experts suggest that it may be considered for post-pubertal girls [BNF for Children, 2012]. Itraconazole is not licensed for use in children [ABPI Medicines Compendium, 2013n].

Adverse effects

There is evidence from a number of RCTs that vulval burning and vaginal discharge are more common with intravaginal imidazoles, whilst nausea, headache, and abdominal pain are more common with oral imidazoles.

There is no evidence that antifungal treatments used appropriately have serious adverse effects.

Treatments not recommended

Topical nystatin. There is evidence that topical nystatin is effective for treating uncomplicated vulvovaginal candidiasis. However, nystatin intravaginal cream and pessaries are no longer available in the UK [MeReC, 2004f; BASHH, 2007h].

Oral ketoconazole — the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections [MHRA, 2013j]. The decision was made because some people taking these medicines may be at an increased risk of liver damage and the risk outweighs the benefits. Alternative antifungal treatments are available.

Povidone-iodine is an antiseptic available in topical intravaginal formulations and is licensed for the treatment of candidal infections of the vagina. However, there is little published evidence to support its use.

Managing treatment failure

How should I manage treatment failure in uncomplicated vulvovaginal candidiasis?

Check that treatments have been used as recommended.

Topical treatments can cause vulvovaginal irritation, so consider this if symptoms persist or worsen.

Consider alternative diagnoses — wrong diagnosis is a common cause for treatment failure.

Measure vaginal pH if possible to assess the likelihood of symptoms being due to Candida (pH less than or equal to 4.5), bacterial vaginosis (pH above 4.5), or Trichomonas vaginalis (pH above 4.5).

Send a vaginal specimen for microscopy and culture to identify:

Non-albicans Candida species (if feasible).

A mixed infection such as candidiasis together with bacterial vaginosis or trichomoniasis (up to 10% of infections are mixed). See the CKS topics on Bacterial vaginosis and Trichomoniasis.

Reassess for predisposing risk factors, and remove or control as far as possible.

Treat:

If there has been a lack of concordance with an intravaginal imidazole, prescribe a short course of an oral antifungal (e.g. fluconazole or itraconazole).

If concordance is good and symptoms are improving, consider treating with an extended course (depending on clinical judgement) of an oral (e.g. itraconazole or fluconazole) or an intravaginal (e.g. clotrimazole, econazole, or miconazole) antifungal.

For girls aged between 12 and 16 years, seek specialist advice.

For vulval symptoms, consider using a topical imidazole (clotrimazole, or ketoconazole) in addition to an oral or intravaginal antifungal.

Refer, or seek specialist advice, if:

Symptoms are not improving and treatment failure is unexplained.

A non-albicans Candida species has been identified.

Treatment fails again.

Diagnosis is unclear.

Basis for recommendation

Basis for recommendation

CKS found no evidence or national guidelines specifically on treatment failure of uncomplicated vulvovaginal candidiasis, which usually responds well to treatment.

Adverse effects

There is evidence from a number of randomized controlled trials that vulval burning and vaginal discharge are more common with intravaginal imidazoles, whilst nausea, headache, and abdominal pain are more common with oral imidazoles.

There is no evidence that antifungal treatments used appropriately have serious adverse effects.

Review and investigations

These recommendations are pragmatic advice.

A vaginal pH reading is recommended in treatment failure to assess the likelihood of symptoms being due to candida [FSRH, 2012a].

Guidelines recommend sending a vaginal swab for fungal microscopy and culture [BASHH, 2006c; CDC, 2006l; RCGP and BASHH, 2006; BASHH, 2007h; FSRH, 2012a].

Treatment

CKS found no evidence or national guidelines to inform treatment decisions. Therefore our current recommendations are unchanged from the previous version of this topic and are pragmatic advice. Where possible CKS has recommended preparations that are licensed for extended use.

Guidelines developed by the Faculty of Sexual and Reproductive Healthcare (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings suggest vulval application of imidazoles for symptom relief but state that they may cause irritation and that there is little evidence that they are more beneficial than emollients [FSRH, 2012a].

Pre- and post-pubertal girls

The recommendation to seek specialist advice in girls aged between 12 to 16 years is based on the fact that making a decision about the route of treatment may not be straightforward in this group.

Oral fluconazole is not licensed for use in children less than 16 years old for the treatment of vaginal candidiasis [ABPI Medicines Compendium, 2012fp]. However experts suggest that it may be considered for post-pubertal girls [BNF for Children, 2012].

Experts do not recommend the use of intravaginal pessaries or cream in pre-pubertal girls [BNF for Children, 2012].

Treatments not recommended

Oral ketoconazole — the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections [MHRA, 2013j]. The decision was made because some people taking these medicines may be at an increased risk of liver damage and the risk outweighs the benefits. Alternative antifungal treatments are available.

Povidone-iodine is an antiseptic available in topical intravaginal formulations and is licensed for the treatment of candidal infections of the vagina. However, there is little published evidence to support its use.

Referral

Expert opinion from reviewers of this CKS topic agreed with our recommendation to seek specialist advice if the woman was compliant with treatment but not improving. One reviewer commented that it was important to identify the isolate and perform specific susceptibility testing, and to look for unresolved underlying pre-disposing factors.

Non-albicans Candida species identified

CKS recommends seeking specialist advice if a non-albicans Candida species is identified because the United Kingdom National Guideline on the management of vulvovaginal candidiasis published by the clinical effectiveness group of the British Society of Sexual Health and HIV (BASHH) states that there may be resistance issues with some organisms and longer antifungal treatment courses may be required. In some people with resistant organisms, treatment that can only be initiated by a specialist or is difficult to obtain in primary care may be required [BASHH, 2007h].

General advice on self-management

What general advice can I give about self-management of the current infection?

Advise women about the following personal hygiene measures and how to avoid potential irritants:

Use a soap substitute to clean the vulval area and do not clean the vulval area more than once per day.

Use emollients as moisturisers several times a day to protect the skin. Use an emollient in the bath.

Avoid potential irritants in toiletries, antiseptics, douches, wipes, and 'feminine hygiene' products.

Avoid washing underwear in biological washing powder and avoid fabric conditioners.

Probiotics (such as live yoghurts) may be used orally or topically. Although there is no evidence that they are effective, there is no evidence of (or concern about) adverse effects.

Do not advise the use of tea tree oil as there is insufficient evidence to recommend its use.

Avoiding tight-fitting clothing is advised in guidelines but there is no evidence for this.

Basis for recommendation

Basis for recommendation

General care

The advice on the general care of vulval skin and the use of emollients is based on expert advice in the guideline: The management of vulval skin disorders published by the Royal College of Obstetricians and Gynaecologists [RCOG, 2011].

Local irritants

CKS found no evidence that local irritants such as soaps and shower gels increase the risk of vulvovaginal candidiasis. However, avoiding local irritants is widely recommended in guidelines [RCGP and BASHH, 2006; BASHH, 2007; RCOG, 2011].

Probiotics

A guideline developed by the Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Healthcare (FSRH) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend the use of probiotics [FSRH, 2012].

Although there is no good evidence of effectiveness in treating or preventing acute or recurrent vulvovaginal candidiasis, there is no evidence of (or concern about) harm.

Dietary changes

A guideline developed by the CEU of the FSRH in collaboration with BASHH on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend a change in diet for women with vulvovaginal candidiasis [FSRH, 2012].

Tea tree oil

A guideline developed by the CEU of the FSRH in collaboration with BASHH on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend the use of tea tree oil in the management of vulvovaginal candidiasis [FSRH, 2012].

Tight-fitting clothes

There is no evidence to suggest that tight-fitting clothing or non-cotton underwear is a risk factor for vulvovaginal candidiasis [Sobel, 2007]. However, avoiding tight-fitting clothing is widely recommended in guidelines [RCGP and BASHH, 2006; BASHH, 2007; RCOG, 2011].

Expert opinion in a guideline developed by the CEU of the FSRH in collaboration with BASHH on the management of vaginal discharge in non-genitourinary medicine settings is that there is currently insufficient evidence to recommend advising against wearing tight clothing [FSRH, 2012].

Treating a sexual partner

When should I treat the sexual partner of a woman with vulvovaginal candidiasis?

Treat the sexual partner only if they are symptomatic.

Rarely, the male partner of a woman with vulvovaginal candidiasis may have symptoms of balanitis. This should be treated with a topical or oral antifungal. See the CKS topic on Balanitis for more detailed information.

There is no need to investigate or treat an asymptomatic partner.

Basis for recommendation

Basis for recommendation

There is some evidence that treating an asymptomatic male partner is of little or no benefit in reducing the woman's risk of reinfection/recurrence. Guidelines recommend that asymptomatic male partners should not be treated [CDC, 2006; BASHH, 2007; FSRH, 2012].

Contraceptive advice

What advice should I give about contraception?

Advise the woman and her partner that some vaginal/vulval antifungal treatments (such as preparations containing clotrimazole, econazole, fenticonazole, and miconazole) may damage latex contraceptives. Advise abstinence or the use of non-latex barrier methods during use, and for several days after, stopping the antifungal treatment.

Advise women using:

Combined hormonal contraception that:

There is limited evidence on the risk of vulvovaginal candidiasis in users of combined oral contraceptives.

Limited evidence suggests that women with recurrent vulvovaginal candidiasis may benefit from switching to a progestogen-only injectable form of contraception. There is a lack of evidence on the effect of switching to other progestogen-only forms of contraception.

The copper intrauterine device that:

There is no consistent evidence of an association with vulvovaginal candidiasis.

The levonorgestrel-releasing intrauterine system (LNG-IUS) that users of this method do not have an increased rate of symptomatic infection although they do have an increased presence of Candida.

The combined vaginal ring that there appears to be no effect on the number of pathogenic bacteria or inflammatory cells, although users have been reported to experience more vaginal discharge and irritation compared with combined hormonal contraceptive users.

Basis for recommendation

Basis for recommendation

These recommendations are based on guidelines developed by the Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Healthcare (FSRH) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012].

Avoiding sex for several days if a latex barrier method is used

This recommendation is pragmatic and based on expert opinion. The guideline does not provide any information about the length of time that abstinence or avoidance of latex condoms should be practised [FSRH, 2012].

Effect of combined hormonal contraception on vulvovaginal candidiasis

It is known that vulvovaginal candidiasis is more common if the vagina is exposed to oestrogen; however, evidence is contradictory about whether combined hormonal contraception increases the risk of vulvovaginal candidiasis [FSRH, 2012].

Progestogen-only injectable contraception

There is evidence from one study that women using a progestogen-only injectable may be less susceptible to developing vulvovaginal candidiasis [FSRH, 2012].

Scenario: Severe infection

Scenario: Severe female genital candida infection

144months3060monthsFemale

Treating severe candidiasis

How should I treat severe vulvovaginal candidiasis?

Send a vaginal specimen for microscopy and culture to confirm the diagnosis. This may identify:

Non-albicans Candida species.

A mixed infection such as candidiasis together with bacterial vaginosis or trichomoniasis (up to 10% of infections are mixed). See the CKS topics on Bacterial vaginosis and Trichomoniasis.

Treat with either two doses of oral fluconazole (150 mg) 3 days apart, or, if oral treatment is contraindicated, use one clotrimazole 500 mg pessary and repeat 3 days later.

Choice of antifungal will depend upon a number of factors, including the woman's preference.

For girls aged between 12 and 16 years, seek specialist advice.

For vulval symptoms, consider prescribing a topical imidazole cream (for example, clotrimazole) in addition to an oral or intravaginal antifungal.

Clotrimazole is available as combination pack containing a 10% vaginal cream and a 2% topical cream (Canesten® Cream Combi) and a combination pack containing a 500 mg vaginal pessary and a 2% topical cream (Canesten® Combi).

Clotrimazole cream may also be bought over-the-counter.

Intravaginal econazole and miconazole may also be applied directly to the vulva to manage vulval symptoms.

Advise the woman to return if symptoms have not resolved within 7–14 days.

Basis for recommendation

Basis for recommendation

These recommendations are based on published expert opinion and one randomized controlled trial (RCT) [CDC, 2006l; BASHH, 2007h].

Confirming the diagnosis

This recommendation is pragmatic and is based on what CKS considers to be accepted clinical practice.

Oral antifungals

One RCT (n = 398) found that women with severe vulvovaginal candidiasis achieved superior clinical and mycological eradication with two sequential 150 mg doses of fluconazole given 3 days apart, compared with a single dose of fluconazole [Sobel et al, 2001a].

CKS did not find any evidence that extended courses of oral itraconazole were effective for severe vulvovaginal candidiasis.

Treatment

CKS did not find any evidence that extended courses of intravaginal imidazoles improved cure rates for severe vulvovaginal candidiasis.

The United Kingdom National Guideline on the Management of Vulvovaginal Candidiasis published by the clinical effectiveness group of the British Society of Sexual Health and HIV (BASHH) recommends a dose of oral fluconazole 150 mg repeated after 3 days. If an oral azole is contraindicated then BASHH recommends a single dose pessary, repeated after 3 days. This is because there is no evidence that 7 days of topical treatment is any more effective than a single dose of an oral azole. Therefore BASHH have concluded that it is more logical to repeat the single dose after 3 days rather than give local treatment for 14 days [BASHH, 2007h].

The Centers for Disease Control and Prevention recommend either a 7–14 day course of a topical azole or two doses of oral fluconazole (150 mg) taken 72 hours apart [CDC, 2006l].

Pre- and post-pubertal girls

The recommendation to seek specialist advice in girls aged between 12 to 16 years is based on the fact that making a decision about the route of treatment may not be straightforward in this group.

Oral fluconazole is not licensed for use in children less than 16 years old for the treatment of vaginal candidiasis [ABPI Medicines Compendium, 2012fp]. However experts suggest that it may be considered for post-pubertal girls [BNF for Children, 2012]. Itraconazole is not licensed for use in children [ABPI Medicines Compendium, 2013n].

Experts do not recommend the use of intravaginal pessaries or cream in pre-pubertal girls [BNF for Children, 2012].

Symptom control

Expert opinion in guidelines developed by the Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Health Care (FSRH) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings suggests vulval application of imidazoles for symptom relief but state that this may cause irritation, and that there is little evidence that they are more beneficial than emollients [FSRH, 2012a].

Adverse effects

There is evidence from a number of RCTs that vulval burning and vaginal discharge are more common with intravaginal imidazoles, whilst nausea, headache, and abdominal pain are more common with oral imidazoles.

There is no evidence that antifungal treatments used appropriately have serious adverse effects.

Treatments not recommended

Topical nystatin. There is evidence that topical nystatin is effective for treating uncomplicated vulvovaginal candidiasis. However, nystatin intravaginal cream and pessaries are no longer available in the UK. [MeReC, 2004f; BASHH, 2007h].

Oral ketoconazole — the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections [MHRA, 2013j]. The decision was made because some people taking these medicines may be at an increased risk of liver damage and the risk outweighs the benefits. Alternative antifungal treatments are available.

Povidone-iodine is an antiseptic available in topical intravaginal formulations and is licensed for the treatment of candidal infections of the vagina. However, there is little published evidence to support its use.

Managing treatment failure

How should I manage treatment failure in severe vulvovaginal candidiasis?

Check that treatments have been used as recommended.

Topical treatments can cause vulvovaginal irritation, so consider this if symptoms persist or worsen.

Consider alternative diagnoses — a wrong diagnosis is a common cause for treatment failure.

Measure vaginal pH if possible to assess the likelihood of symptoms being due to candida (pH less than or equal to 4.5), bacterial vaginosis (pH above 4.5), or Trichomonas vaginalis (pH above 4.5).

Send a vaginal specimen for culture to identify:

A non-albicans Candida species (if feasible).

A mixed infection such as candidiasis together with bacterial vaginosis or trichomoniasis (up to 10% of infections are mixed). See the CKS topics on Bacterial vaginosis and Trichomoniasis.

Reassess for predisposing risk factors, and remove or control as far as possible.

Treat:

If there has been a lack of concordance with an intravaginal imidazole, prescribe a course of oral fluconazole 150 mg (two doses 3 days apart) unless contraindicated.

If there has been a lack of concordance with oral fluconazole, prescribe clotrimazole pessaries 500 mg (two doses 3 days apart).

For girls aged between 12 and 16 years, seek specialist advice.

For persistent vulval symptoms, consider prescribing a topical imidazole (clotrimazole, or ketoconazole) in addition to an oral or intravaginal antifungal.

Refer, or seek specialist advice, if:

Symptoms have not improved and treatment failure is unexplained.

Treatment fails again.

A non-albicans Candida species is identified.

Basis for recommendation

Basis for recommendation

CKS found no evidence or national guidelines specifically on treatment failure of uncomplicated vulvovaginal candidiasis, which usually responds well to treatment.

Review and investigation

These recommendations are pragmatic advice.

A vaginal pH reading can be useful to assess the likelihood of symptoms being due to Candida rather than bacterial vaginosis or trichomoniasis [FSRH, 2012a].

Guidelines recommend sending a vaginal swab for fungal microscopy and culture [BASHH, 2006c; CDC, 2006l; RCGP and BASHH, 2006; BASHH, 2007h; FSRH, 2012a].

Treatment

CKS found no evidence or national guidelines specifically on treatment failure of severe vulvovaginal candidiasis. These recommendations are therefore pragmatic advice, consistent with expert opinion from reviewers of this CKS topic.

Expert opinion in guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings suggest vulval application of imidazoles for symptom relief but state that they may cause irritation and that there is little evidence that they are more beneficial than emollients [FSRH, 2012a].

Pre- and post-pubertal girls

The recommendation to seek specialist advice in girls aged between 12 to 16 years is based on the fact that making a decision about the route of treatment may not be straightforward in this group.

Oral fluconazole is not licensed for use in children less than 16 years old for the treatment of vaginal candidiasis [ABPI Medicines Compendium, 2012fp]. However experts suggest that it may be considered for post-pubertal girls [BNF for Children, 2012].

Experts do not recommend the use of intravaginal pessaries or cream in pre-pubertal girls [BNF for Children, 2012].

Treatments not recommended

Topical nystatin. There is evidence that topical nystatin is effective for treating uncomplicated vulvovaginal candidiasis. However nystatin intravaginal cream and pessaries are no longer available in the UK [MeReC, 2004f; BASHH, 2007h].

Oral ketoconazole — the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections [MHRA, 2013j]. The decision was made because some people taking these medicines may be at an increased risk of liver damage and the risk outweighs the benefits. Alternative antifungal treatments are available.

Povidone-iodine is an antiseptic available in topical intravaginal formulations and is licensed for the treatment of candidal infections of the vagina. However, there is little published evidence to support its use.

Referral

Expert opinion from reviewers of this CKS topic agreed with the recommendation to seek specialist advice if the woman has not improved on treatment.

Non albicans Candida species identified

CKS recommends seeking specialist advice if a non-albicans Candida species is identified because the United Kingdom National Guideline on the management of vulvovaginal candidiasis published by the clinical effectiveness group of the British Society of Sexual Health and HIV (BASHH) states that there may be resistance issues with some organisms and longer antifungal treatment courses may be required. In some people with resistant organisms, treatment that can only be initiated by a specialist or is difficult to obtain in primary care may be required [BASHH, 2007h].

General advice on self-management

What general advice can I give about self-management of the current infection?

Advise women about the following personal hygiene measures and how to avoid potential irritants:

Use a soap substitute to clean the vulval area and do not clean the vulval area more than once per day.

Use emollients as moisturisers several times a day to protect the skin. Use an emollient in the bath.

Avoid potential irritants in toiletries, antiseptics, douches, wipes, and 'feminine hygiene' products.

Avoid washing underwear in biological washing powder and avoid fabric conditioners.

Probiotics (such as live yoghurts) may be used orally or topically. Although there is no evidence that they are effective, there is no evidence of (or concern about) adverse effects.

Do not advise the use of tea tree oil as there is insufficient evidence to recommend its use.

Avoiding tight-fitting clothing is advised in guidelines but there is no evidence for this.

Basis for recommendation

Basis for recommendation

General care

The advice on the general care of vulval skin and the use of emollients is based on expert advice in the guideline: The Management of Vulval Skin Disorders published by the Royal College of Obstetricians and Gynaecologists [RCOG, 2011].

Local irritants

CKS found no evidence that local irritants such as soaps and shower gels increase the risk of vulvovaginal candidiasis. However, avoiding local irritants is widely recommended in guidelines [RCGP and BASHH, 2006; BASHH, 2007; RCOG, 2011].

Probiotics

A guideline developed by the Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Healthcare (FSRH) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend the use of probiotics [FSRH, 2012].

Although there is no good evidence of effectiveness in treating or preventing acute or recurrent vulvovaginal candidiasis, there is no evidence of (or concern about) harm.

Dietary changes

A guideline developed by the CEU of the FSRH in collaboration with BASHH on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend a change in diet for women with vulvovaginal candidiasis [FSRH, 2012].

Tea tree oil

A guideline developed by the CEU of the FSRH are (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with BASHH on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend the use of tea tree oil in the management of vulvovaginal candidiasis [FSRH, 2012].

Tight-fitting clothes

There is no evidence to suggest that tight-fitting clothing or non-cotton underwear is a risk factor for vulvovaginal candidiasis [Sobel, 2007]. However, avoiding tight-fitting clothing is widely recommended in guidelines [RCGP and BASHH, 2006; BASHH, 2007; RCOG, 2011].

Expert opinion in a guideline developed by the CEU of the FSRH in collaboration with BASHH on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend advising against wearing tight clothing [FSRH, 2012].

Treating a sexual partner

When should I treat the sexual partner of a woman with vulvovaginal candidiasis?

Treat the sexual partner only if they are symptomatic.

Rarely, the male partner of a woman with vulvovaginal candidiasis may have symptoms of balanitis. This should be treated with a topical or oral antifungal. See the CKS topic on Balanitis for more detailed information.

There is no need to investigate or treat an asymptomatic partner.

Basis for recommendation

Basis for recommendation

There is some evidence that treating an asymptomatic male partner is of little or no benefit in reducing the woman's risk of reinfection/recurrence. Guidelines recommend that asymptomatic male partners should not be treated [CDC, 2006; BASHH, 2007; FSRH, 2012].

Contraceptive advice

What advice should I give about contraception?

Advise the woman and her partner that some vaginal/vulval antifungal treatments (such as preparations containing clotrimazole, econazole, fenticonazole, and miconazole) may damage latex contraceptives. Advise abstinence or the use of non-latex barrier methods during use, and for several days after, stopping the antifungal treatment.

Advise women using:

Combined hormonal contraception that:

There is limited evidence on the risk of vulvovaginal candidiasis in users of combined oral contraceptives.

Limited evidence suggests that women with recurrent vulvovaginal candidiasis may benefit from switching to a progestogen-only injectable form of contraception. There is a lack of evidence on the effect of switching to other progestogen-only forms of contraception.

The copper intrauterine device that there is no consistent evidence of an association with vulvovaginal candidiasis.

The levonorgestrel-releasing intrauterine system (LNG-IUS) that users of this method do not have an increased rate of symptomatic infection although they do have an increased presence of Candida.

The combined vaginal ring that there appears to be no effect on the number of pathogenic bacteria or inflammatory cells, although users have been reported to experience more vaginal discharge and irritation compared with combined hormonal contraceptive users.

Basis for recommendation

Basis for recommendation

These recommendations are based on guidelines developed by the Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Healthcare (FSRH) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012].

Avoiding sex for several days if a latex barrier method is used

This recommendation is pragmatic and based on expert opinion. The guideline does not provide any information about the length of time that abstinence or avoidance of latex condoms should be practised [FSRH, 2012].

Effect of combined hormonal contraception on vulvovaginal candidiasis

It is known that vulvovaginal candidiasis is more common if the vagina is exposed to oestrogen; however, evidence is contradictory about whether combined hormonal contraception increases the risk of vulvovaginal candidiasis [FSRH, 2012].

Progestogen-only injectable contraception

There is evidence from one study that women using a progestogen-only injectable may be less susceptible to developing vulvovaginal candidiasis [FSRH, 2012].

Scenario: Recurrent infection

Scenario: Recurrent female genital Candida infection

144months3060monthsFemale

Managing recurrent infection

How do I manage recurrent vulvovaginal candidiasis infection?

Eliminate or control predisposing risk factors as far as is practical.

Measure vaginal pH if possible to assess the likelihood of symptoms being due to candida (pH less than or equal to 4.5), or bacterial vaginosis (pH above 4.5) or Trichomonas vaginalis (pH above 4.5).

Take a high vaginal swab for microscopy and speciated culture to confirm the diagnosis, and identify the presence of:

A moderate/heavy growth of Candida albicans when symptomatic on at least two occasions.

Non-albicans Candida species.

A mixed infection such as candidiasis with bacterial vaginosis or trichomoniasis (up to 10% of infections are mixed). See the CKS topics on Bacterial vaginosis and Trichomoniasis.

Consider alternative diagnoses if a woman has recurrent or persistent symptoms.

Treat the presenting episode with a longer course of an antifungal drug (induction course). Two options are:

Three doses of fluconazole 150 mg. One 150 mg dose to be taken every 72 hours, or

Topical imidazole therapy for 10–14 days according to symptomatic response.

For vulval symptoms, consider using a topical antifungal cream, in addition to the oral or intravaginal antifungal.

Once the induction course is completed, offer:

Either 'treatment as required' with a prescription to be used if symptoms recur,

Or a maintenance regimen of 6 months' treatment with an oral or intravaginal antifungal (off-label use). Options for maintenance therapy include:

Intravaginal clotrimazole 500 mg once a week.

Oral fluconazole 150 mg once a week.

Oral itraconazole 50–100 mg daily.

Review after 6 months of treatment.

If, after completing a course of maintenance therapy, vulvovaginal candidiasis recurs infrequently, treat each episode independently. If recurrent disease is troublesome, repeat the induction and maintenance regimens.

The choice of antifungal and route (oral or intravaginal) will depend upon a number of factors. Most women prefer oral products to intravaginal creams or pessaries, especially for longer-term use.

For girls aged between 12 and 16 years, seek specialist advice.

Seek specialist advice for the treatment of recurrent non-albicans Candida species infections.

Basis for recommendation

Basis for recommendation

Measuring vaginal pH

A vaginal pH reading can be useful to assess the likelihood of symptoms being due to Candida rather than bacterial vaginosis or trichomoniasis [FSRH, 2012a].

Obtaining fungal cultures from vaginal secretions

Vaginal cultures should be obtained to confirm the clinical diagnosis and to identify unusual species, including non-albicans Candida species, because:

Candida glabrata and other non-albicans Candida species are observed in 10–20% of women with recurrent vulvovaginal candidiasis [CDC, 2006l].

Conventional antimycotic therapies are often not as effective against these species [CDC, 2006l].

Empiric self-treatment

One small crossover RCT (23 participants) provides weak evidence that a majority of women might prefer self-treatment, although regular maintenance therapy is more effective [Fong, 1994].

Induction treatment

Induction therapy ensures clinical remission and is followed immediately by maintenance therapy [BASHH, 2007h].

Oral fluconazole or topical imidazole treatment are recommended by the Clinical Effectiveness Group of the British Association of Sexual Health and HIV in their United Kingdom National Guideline on the management of vulvovaginal candidiasis [BASHH, 2007h], and the British National Formulary [BNF 63, 2012]. Oral fluconazole is recommended in guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012a].

Maintenance treatment

CKS recommends intravaginal clotrimazole, oral fluconazole, and oral itraconazole for maintenance treatment, as these have been assessed in clinical trials and are recommended in published guidelines [BASHH, 2007h; FSRH, 2012a] and the British National Formulary [BNF 63, 2012].

There is evidence from randomized controlled trials (RCTs) that maintenance therapy with weekly oral fluconazole, monthly oral itraconazole, or monthly intravaginal clotrimazole reduces rates of recurrence of vulvovaginal candidiasis. Recurrence rates increase when maintenance treatment is stopped, but in one trial important clinical benefits remained for at least 6 months for women who had used oral fluconazole [Sobel et al, 2004]. In this trial oral fluconazole was used for induction (150 mg for three doses followed by 150 mg once a week for 6 months) and approximately 90% of participants did not have a recurrence of vulvovaginal candidiasis after 6 months, and 40% after 1 year.

Some UK guidelines [BASHH, 2007h; FSRH, 2012a] recommend the use of ketoconazole as maintenance treatment. However CKS have not recommended this as the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections [MHRA, 2013j]. The decision was made because some people taking these medicines may be at an increased risk of liver damage and the risk outweighs the benefits. Alternative antifungal treatments are available.

Guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012a] recommend oral fluconazole 150 mg once weekly and fluconazole 50 mg daily or itraconazole 50–100 mg daily as an alternative maintenance regimen.

One small observational study reported that women preferred oral to intravaginal treatments for recurrent candidiasis [Kovacs et al, 1990b].

Non albicans Candida species identified

CKS recommends seeking specialist advice if a non-albicans Candida species is identified because the United Kingdom National Guideline on the management of vulvovaginal candidiasis published by the clinical effectiveness group of the British Society of Sexual Health and HIV (BASHH) states that there may be resistance issues with some organisms and longer antifungal treatment courses may be required. In some people with resistant organisms, treatment that can only be initiated by a specialist or is difficult to obtain in primary care may be required [BASHH, 2007h].

Pre- and post-pubertal girls

The recommendation to seek specialist advice in girls aged between 12 to 16 years is based on the fact that making a decision about the route of treatment may not be straightforward in this group.

Oral fluconazole is not licensed for use in children less than 16 years old for the treatment of vaginal candidiasis [ABPI Medicines Compendium, 2012fp]. However experts suggest that it may be considered for post-pubertal girls [BNF for Children, 2012].

Experts do not recommend the use of intravaginal pessaries or cream in pre-pubertal girls [BNF for Children, 2012].

Adverse effects

There is evidence from a number of RCTs that vulval burning and vaginal discharge are more common with intravaginal imidazoles, whilst nausea, headache, and abdominal pain are more common with oral imidazoles.

There is no evidence that antifungal treatments used appropriately have serious adverse effects.

Other treatment

Povidone-iodine is an antiseptic available in topical intravaginal formulations and is licensed for the treatment of candidal infections of the vagina. However, there is little published evidence to support its use.

Treating a sexual partner

When should I treat the sexual partner of a woman with vulvovaginal candidiasis?

Treat the sexual partner only if they are symptomatic.

Rarely, the male partner of a woman with vulvovaginal candidiasis has symptoms of balanitis, and this should be treated with a topical or oral antifungal. See the CKS topic on Balanitis for more detailed information.

There is no need to investigate or treat an asymptomatic partner.

Basis for recommendation

Basis for recommendation

There is some evidence that treating an asymptomatic male partner is of little or no benefit in reducing the woman's risk of reinfection/recurrence. Guidelines recommend that asymptomatic male partners not be treated [CDC, 2006; BASHH, 2007; FSRH, 2012].

Self-management of future episodes

What advice can I give about self-management of future episodes?

Advise the woman that:

If a similar episode occurs in the future, oral and topical treatments can be bought at pharmacies, and no prescription will be required.

Over-the-counter products should not be used over the longer term without medical advice.

She should return for assessment by a healthcare professional if she:

Is under 16 or over 60 years of age.

Is pregnant.

Has abnormal menstrual bleeding or lower abdominal pain.

Develops systemic symptoms.

Has symptoms that are not entirely consistent with a previous episode (for example the discharge is coloured or malodorous, or there are ulcers or blisters).

Has symptoms that do not settle after use of over-the-counter products.

Has had two episodes in 6 months, and has not consulted a healthcare professional about the condition for more than a year.

Has had a previous sexually transmitted infection (herself or her partner).

Has had a previous adverse reaction to an antifungal drug, or antifungal drugs have proved ineffective.

Basis for recommendation

Basis for recommendation

This advice is based upon expert opinion from the published medical literature [Nyirjesy, 2001; Watson and Bond, 2003; CDC, 2006; Sobel, 2007].

Self diagnosis

Up to two-thirds of women who have self-diagnosed uncomplicated candidiasis do not actually have the condition [Nyirjesy et al, 1997; Ferris et al, 2002].

Over-the-counter preparations

Guidelines state that unnecessary or inappropriate use of over-the-counter preparations can lead to a delay in the treatment of other vulvovaginal conditions [CDC, 2006].

Contraceptive advice

What advice should I give about contraception?

Advise the woman and her partner that some vaginal/vulval antifungal treatments (such as preparations containing clotrimazole, econazole, fenticonazole, and miconazole) may damage latex contraceptives. Advise abstinence or the use of non-latex barrier methods during use, and for several days after, stopping the antifungal treatment.

Advise women using:

Combined hormonal contraception that:

There is limited evidence on the risk of vulvovaginal candidiasis in users of combined oral contraceptives.

Limited evidence suggests that women with recurrent vulvovaginal candidiasis may benefit from switching to a progestogen-only injectable form of contraception. There is a lack of evidence on the effect of switching to other progestogen-only forms of contraception.

The copper intrauterine device that there is no consistent evidence of an association with vulvovaginal candidiasis.

The levonorgestrel-releasing intrauterine system (LNG-IUS) that users of this method do not have an increased rate of symptomatic infection although they do have an increased presence of Candida.

The combined vaginal ring that there appears to be no effect on the number of pathogenic bacteria or inflammatory cells, although users have been reported to experience more vaginal discharge and irritation compared with combined hormonal contraceptive users.

Basis for recommendation

Basis for recommendation

These recommendations are based on guidelines developed by the Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Healthcare (FSRH) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012].

Avoiding sex for several days if a latex barrier method is used

This recommendation is pragmatic and based on expert opinion. The guideline does not provide any information about the length of time that abstinence or avoidance of latex condoms should be practised [FSRH, 2012].

Effect of combined hormonal contraception on vulvovaginal candidiasis

It is known that vulvovaginal candidiasis is more common if the vagina is exposed to oestrogen; however, evidence is contradictory about whether combined hormonal contraception increases the risk of vulvovaginal candidiasis [FSRH, 2012].

Progestogen-only injectable contraception

There is evidence from one study that women using a progestogen-only injectable may be less susceptible to developing vulvovaginal candidiasis [FSRH, 2012].

Scenario: During pregnancy

Scenario: Vulvovaginal candidiasis during pregnancy

144months3060monthsFemale

Managing infection in pregnancy

How should I manage vulvovaginal candidiasis in women who are pregnant?

Treat with intravaginal clotrimazole or miconazole for at least 7 days.

Do not use oral antifungals such as fluconazole and itraconazole.

Advise the woman that care should be taken when using an applicator during pregnancy to avoid physical damage to the cervix. Some women prefer to insert pessaries by hand when pregnant.

For vulval symptoms, consider prescribing topical clotrimazole cream in addition to intravaginal clotrimazole or miconazole.

Intravaginal miconazole can also be applied directly to the vulva to manage vulval symptoms.

Clotrimazole is available as combination pack containing a 10% vaginal cream and a 2% topical cream (Canesten® Cream Combi) and a combination pack containing a 500 mg vaginal pessary and a 2% topical cream (Canesten® Combi).

Advise the woman to return if symptoms have not resolved within 7–14 days.

Refer the woman to a genito-urinary medicine clinic if sexually transmitted infection is suspected.

Basis for recommendation

Basis for recommendation

These recommendations are based on published expert opinion from the medical literature and a systematic review [Young and Jewell, 2001; CDC, 2006; BASHH, 2007; FSRH, 2012].

There is evidence that treatment with topical imidazoles is more effective than topical nystatin in the treatment of pregnant women with vulvovaginal candidiasis, and that longer courses (7 days) cured more than 90% of women whereas standard (4-day) courses only cured about half the cases [Young and Jewell, 2001]. A seven day course is recommended by the Clinical Effectiveness group of the British Association of Sexual Health and HIV (BASHH) [BASHH, 2007] and also in guidelines developed by the Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Health Care (FSRH) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012].

Safety

Clotrimazole and miconazole are considered safe to use in pregnant women.

The available data suggest that there is no evidence of an increased risk of spontaneous abortions or malformations with clotrimazole compared with the background rate [NTIS, 2008; ABPI Medicines Compendium, 2010a].

Miconazole has shown no fetotoxic effect in animal studies. It is fetotoxic in high oral doses. Only small amounts of miconazole are absorbed after topical administration [ABPI Medicines Compendium, 2009].

Other topical imidazoles are not recommended:

Although the available data do not indicate an increased risk of teratogenicity, there are fewer data on exposure to topical econazole and fenticonazole during pregnancy than data on clotrimazole and miconazole [Schaefer et al, 2007].

The manufacturer of econazole states 'it should not be used in pregnancy unless the clinician considers it to be necessary' [ABPI Medicines Compendium, 2012a]. In animal studies, econazole was not shown to be teratogenic, but was fetotoxic. The significance of this effect in humans is unknown.

Fenticonazole and its metabolites cross the placental barrier after vaginal application. Fenticonazole has shown embryotoxic effects and prolonged gestation in rats after oral doses above 40 mg/kg/day. No teratogenic effects were shown in rats or rabbits. As there is very little experience of its use in pregnant women, the manufacturers advise against its use unless essential [ABPI Medicines Compendium, 2010b].

CKS therefore recommends using topical clotrimazole or miconazole.

Oral triazoles (fluconazole and itraconazole) are contraindicated in pregnant women.

Animal studies have found that high doses of itraconazole cause fetal abnormalities although there are limited data in humans [Schaefer et al, 2007; ABPI Medicines Compendium, 2013], and there are concerns that fluconazole may cause congenital defects [Schaefer et al, 2007; ABPI Medicines Compendium, 2012b].

Treatment failure in pregnancy

How should I manage treatment failure in women who are pregnant?

Check that treatments have been used as recommended.

Consider alternative diagnoses.

Measure vaginal pH if possible to assess the likelihood of symptoms being due to candida (pH less or equal to 4.5), bacterial vaginosis (pH above 4.5), or Trichomonas vaginalis (pH above 4.5)

Send a vaginal specimen for culture to identify:

A non-albicans Candida species.

A mixed infection such as candidiasis together with bacterial vaginosis or trichomoniasis (up to 10% of infections are mixed). See the CKS topics on Bacterial vaginosis and Trichomoniasis.

Reassess for other predisposing risk factors, and remove or control as far as possible.

Offer further treatment:

If symptoms are improving, consider giving a second course of intravaginal clotrimazole or miconazole.

Do not prescribe oral antifungals such as fluconazole or ketoconazole.

For vulval symptoms, consider prescribing topical clotrimazole cream in addition to intravaginal clotrimazole or miconazole.

Refer, or seek specialist advice if:

Compliance has been a problem because of adverse effects.

Symptoms are not improving and treatment failure is unexplained.

The diagnosis is unclear.

Non-albicans Candida species is identified.

Basis for recommendation

Basis for recommendation

These recommendations are pragmatic advice. CKS found no evidence or national guidelines specifically on treatment failure of vulvovaginal candidiasis in pregnancy.

Review, investigation, referral

These recommendations are pragmatic advice.

A vaginal pH reading is recommended in treatment failure to assess the likelihood of symptoms being due to candida [FSRH, 2012a].

Guidelines recommend sending vaginal swab for fungal microscopy and culture [BASHH, 2006c; CDC, 2006l; RCGP and BASHH, 2006; BASHH, 2007h; FSRH, 2012a].

Treatment

The doses CKS has recommended for extended courses are estimates only, as published reviews and guidelines do not give details of what doses to use. Where possible, CKS has recommended preparations that are licensed for extended use.

Intravaginal nystatin was recommended for non-albicans Candida species because experts believe (on the basis of laboratory evidence) that it is more effective than topical or oral azoles against Candida glabrata and other non-albicans Candida species [BASHH, 2007h]. Nystatin is considered safe in pregnancy [Schaefer et al, 2007a]. However nystatin intravaginal cream and pessaries are no longer available in the UK. CKS recommend seeking specialist advice.

Safety

Clotrimazole and miconazole are considered safe to use in pregnant women.

The available data suggest that there is no evidence of an increased risk of spontaneous abortions or malformations with clotrimazole compared with the background rate [NTIS, 2008l; ABPI Medicines Compendium, 2010b`].

Miconazole has shown no fetotoxic effect in animal studies. It is fetotoxic in high oral doses. Only small amounts of miconazole are absorbed after topical administration [ABPI Medicines Compendium, 2009dg].

Other topical imidazoles are not recommended:

Although the available data do not indicate an increased risk of teratogenicity, there are fewer data on exposure to topical econazole and fenticonazole during pregnancy than data on clotrimazole and miconazole [Schaefer et al, 2007a].

The manufacturer of econazole states 'it should not be used in pregnancy unless the clinician considers it to be necessary' [ABPI Medicines Compendium, 2012t]. In animal studies, econazole was not shown to be teratogenic, but was fetotoxic. The significance of this effect in humans is unknown.

Fenticonazole and its metabolites cross the placental barrier after vaginal application. Fenticonazole has shown embryotoxic effects and prolonged gestation in rats after oral doses above 40 mg/kg/day. No teratogenic effects were shown in rats or rabbits. As there is very little experience of its use in pregnant women, the manufacturers advise against its use unless essential [ABPI Medicines Compendium, 2010eq].

CKS therefore recommends using topical clotrimazole or miconazole.

General advice on self-management

What general advice can I give about self-management of the current infection?

Advise women about the following personal hygiene measures and how to avoid potential irritants:

Use a soap substitute to clean the vulval area and do not clean the vulval area more than once per day.

Use emollients as moisturisers several times a day to protect the skin. Use an emollient in the bath.

Avoid potential irritants in toiletries, antiseptics, douche, wipes, and 'feminine hygiene' products.

Avoid washing underwear in biological washing powder and avoid fabric conditioners.

Probiotics (such as live yoghurts) may be used orally or topically. Although there is no evidence that they are effective, there is no evidence of (or concern about) adverse effects.

Do not advise the use of tea tree oil as there is insufficient evidence to recommend its use.

Avoiding tight-fitting clothing is advised in guidelines but there is no evidence for this.

Basis for recommendation

Basis for recommendation

General care

The advice on the general care of vulval skin and the use of emollients is based on expert opinion in the guideline: The management of vulval skin disorders published by the Royal College of Obstetricians and Gynaecologists [RCOG, 2011].

Local irritants

CKS found no evidence that local irritants such as soaps and shower gels increase the risk of vulvovaginal candidiasis. However, avoiding local irritants is widely recommended in guidelines [RCGP and BASHH, 2006; BASHH, 2007; RCOG, 2011].

Probiotics

A guideline developed by the Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Healthcare (FSRH) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend the use of probiotics [FSRH, 2012].

Although there is no good evidence of effectiveness in treating or preventing acute or recurrent vulvovaginal candidiasis, there is no evidence of (or concern about) harm.

Dietary changes

A guideline developed by the CEU of the FSRH in collaboration with BASHH on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend a change in diet for women with vulvovaginal candidiasis [FSRH, 2012].

Tea tree oil

A guideline developed by the CEU of the FSRH are (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with BASHH on the management of vaginal discharge in non-genitourinary medicine settings states that there is currently insufficient evidence to recommend the use of tea tree oil in the management of vulvovaginal candidiasis [FSRH, 2012].

Tight-fitting clothes

There is no evidence to suggest that tight-fitting clothing or non-cotton underwear is a risk factor for vulvovaginal candidiasis [Sobel, 2007]. However, avoiding tight-fitting clothing is widely recommended in guidelines [RCGP and BASHH, 2006; BASHH, 2007; RCOG, 2011].

Expert opinion in a guideline developed by the CEU of the FSRH in collaboration with BASHH on the management of vaginal discharge in non-genitourinary medicine settings is that there is currently insufficient evidence to recommend advising against wearing tight clothing [FSRH, 2012].

Treating a sexual partner

When should I treat the sexual partner of a woman with vulvovaginal candidiasis?

Treat the sexual partner only if they are symptomatic.

Rarely, the male partner of a woman with vulvovaginal candidiasis may have symptoms of balanitis. This should be treated with a topical or oral antifungal. See the CKS topic on Balanitis for more detailed information.

There is no need to investigate or treat an asymptomatic partner.

Basis for recommendation

Basis for recommendation

There is some evidence that treating an asymptomatic male partner is of little or no benefit in reducing the woman's risk of reinfection/recurrence. Guidelines recommend that asymptomatic male partners should not be treated [CDC, 2006; BASHH, 2007; FSRH, 2012].

Scenario: Diabetes or immunocompromised

Scenario: Vulvovaginal candidiasis and diabetes or immunocompromised

144months3060monthsFemale

Management

How should I manage vulvovaginal candidiasis in women who have diabetes, who are HIV-positive or who are on long-term corticosteroids?

Correct modifiable conditions (such as uncontrolled diabetes).

Treat people with controlled diabetes and HIV exactly the same as people who do not have diabetes or HIV for uncomplicated infection, severe infection, and recurrent infection.

Choice of treatment will depend upon a number of factors, including the person's preference.

In people who are taking oral corticosteroids or who have uncontrolled diabetes, consider treating with an extended course (7 days) of oral antifungals (such as fluconazole or itraconazole), or 6–14 days of intravaginal antifungals (such as clotrimazole, econazole, or miconazole).

For girls aged between 12 and 16 years, seek specialist advice regarding treatment.

Advise the woman to return if:

Symptoms have not resolved within 7–14 days.

She becomes systemically unwell.

Basis for recommendation

Basis for recommendation

These recommendations are based on expert opinion published in the medical literature [CDC, 2006l; BASHH, 2007h; Sobel, 2007a].

Women who have diabetes

The prevalence of vulvovaginal candidiasis is not increased in women with well-controlled diabetes [Sobel, 2007a].

Expert opinion in the United Kingdom National Guideline on the management of vulvovaginal candidiasis published by the clinical effectiveness group of the British Society of Sexual Health and HIV (BASHH) [BASHH, 2007h] states that, if the infection is due to Candida albicans, women with diabetes have a similar response to non-diabetics to oral fluconazole 150 mg.

Women who are HIV positive

Expert opinion in the United Kingdom National Guidelines on the management of vulvovaginal candidiasis published by the clinical effectiveness group of the British Society of Sexual Health and HIV (BASHH) [BASHH, 2007h] and a review article [Sobel, 2007a] recommends that people with HIV and symptomatic vulvovaginal candidiasis (including recurrent infections) should be treated in an identical way to women who are not HIV positive. However vulvovaginal candidiasis does occur more frequently and is more likely to persist in HIV positive women [BASHH, 2007h; FSRH, 2012a] and longer courses of treatment may be required [FSRH, 2012a].

A Cochrane review of the treatment of vulvovaginal candidiasis in women with HIV did not find any randomized controlled trials, so did not make any recommendations on treatment [Ray et al, 2011].

Extended courses

Expert opinion in guidelines from the Centers for Disease Control and Prevention is that women with underlying debilitating medical conditions such as uncontrolled diabetes, or those receiving corticosteroid treatment do not respond as well to short-term therapies [CDC, 2006l].

Pre- and post-pubertal girls

The recommendation to seek specialist advice in girls aged between 12 to 16 years is based on the fact that making a decision about the route of treatment may not be straightforward in this group.

Oral fluconazole is not licensed for use in children less than 16 years old for the treatment of vaginal candidiasis [ABPI Medicines Compendium, 2012fp]. However experts suggest that it may be considered for post-pubertal girls [BNF for Children, 2012].

Experts do not recommend the use of intravaginal pessaries or cream in pre-pubertal girls [BNF for Children, 2012].

Adverse effects

There is evidence from a number of randomized controlled trials that vulval burning and vaginal discharge are more common with intravaginal imidazoles, whilst nausea, headache, and abdominal pain are more common with oral imidazoles.

There is no evidence that antifungal treatments used appropriately have serious adverse effects.

Treatments not recommended

Topical nystatin. There is evidence that topical nystatin is effective for treating uncomplicated vulvovaginal candidiasis. However nystatin intravaginal cream and pessaries are no longer available in the UK [MeReC, 2004f; BASHH, 2007h].

Oral ketoconazole — the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections [MHRA, 2013j]. The decision was made because some people taking these medicines may be at an increased risk of liver damage and the risk outweighs the benefits. Alternative antifungal treatments are available.

Povidone-iodine is an antiseptic available in topical intravaginal formulations and is licensed for the treatment of candidal infections of the vagina. However, there is little published evidence to support its use.

Managing treatment failure

How should I manage treatment failure in women who have diabetes, who are HIV-positive or who are on long-term corticosteroids?

Correct modifiable conditions (such as uncontrolled diabetes).

Check that treatments have been used as recommended.

Topical treatments can cause vulvovaginal irritation, so consider this if symptoms persist or worsen.

Consider alternative diagnoses .

Measure vaginal pH if possible to assess the likelihood of symptoms being due to candida (pH less or equal to 4.5), or bacterial vaginosis (pH above 4.5) or Trichomonas vaginalis (pH above 4.5).

Send a vaginal specimen for culture to identify:

A non-albicans Candida species.

A mixed infection such as candidiasis together with bacterial vaginosis or trichomoniasis (up to 10% of infections are mixed). See the CKS topics on Bacterial vaginosis and Trichomoniasis.

Reassess for other predisposing risk factors, and remove or control as far as possible.

Offer further treatment:

If there has been a lack of concordance with an intravaginal imidazole, prescribe an extended course (7 days) of an oral antifungal (such as fluconazole or itraconazole).

If there has been a lack of concordance with an oral antifungal, then prescribe a course (6–14 days) of an intravaginal imidazole (such as clotrimazole, econazole, or miconazole).

For girls between 12 and 16 years old, seek specialist advice.

For vulval symptoms, consider using a topical imidazole (for example clotrimazole) in addition to an oral or intravaginal antifungal.

Refer, or seek specialist advice, if:

A non-albicans Candida species is identified.

Treatment failure is unexplained.

The woman develops systemic symptoms.

The diagnosis is unclear.

Basis for recommendation

Basis for recommendation

These recommendations are pragmatic advice.

Correcting modifiable conditions

The prevalence of vulvovaginal candidiasis is not increased in women with well-controlled diabetes [Sobel, 2007a]. Expert opinion from a reviewer of this CKS topic emphasizes the importance of optimal glycaemic control.

Adverse effects

There is evidence from a number of randomized controlled trials that vulval burning and vaginal discharge are more common with intravaginal imidazoles, whilst nausea, headache, and abdominal pain are more common with oral imidazoles.

There is no evidence that antifungal treatments used appropriately have serious adverse effects.

Review and investigation

A vaginal pH reading is recommended in treatment failure to assess the likelihood of symptoms being due to candida [FSRH, 2012a].

Guidelines recommend sending a vaginal swab for fungal microscopy and culture [BASHH, 2006c; CDC, 2006l; RCGP and BASHH, 2006; BASHH, 2007h; FSRH, 2012a].

There is an increased prevalence of non-albicans Candida in women with type 2 diabetes [BASHH, 2007h].

Treatment

There are no published guidelines for women with vulvovaginal candidiasis who have diabetes, are HIV positive or who are on corticosteroids and experience treatment failure.

CKS was not able to find any evidence to inform management, therefore this recommendation is pragmatic advice. Expert opinion from reviewers of this CKS topic agrees with prescribing an extended course of oral antifungals if there has been a lack of concordance with an intravaginal imidazole.

Guidelines developed by the Faculty of Sexual and Reproductive Healthcare (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings suggest vulval application of imidazoles for symptom relief but state that they may cause irritation and that there is little evidence that they are more beneficial than emollients [FSRH, 2012a].

Pre- and post-pubertal girls

The recommendation to seek specialist advice in girls aged between 12 to 16 years is based on the fact that making a decision about the route of treatment may not be straightforward in this group.

Oral fluconazole is not licensed for use in children less than 16 years old for the treatment of vaginal candidiasis [ABPI Medicines Compendium, 2012fp]. However experts suggest that it may be considered for post-pubertal girls [BNF for Children, 2012].

Experts do not recommend the use of intravaginal pessaries or cream in pre-pubertal girls [BNF for Children, 2012].

Treatments not recommended

Oral ketoconazole — the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has suspended the marketing authorisation for oral ketoconazole, and it should not be prescribed for the treatment of fungal infections [MHRA, 2013j]. The decision was made because some people taking these medicines may be at an increased risk of liver damage and the risk outweighs the benefits. Alternative antifungal treatments are available.

Povidone-iodine is an antiseptic available in topical intravaginal formulations and is licensed for the treatment of candidal infections of the vagina. However, there is little published evidence to support its use.

Referral

Expert opinion from reviewers of this CKS topic agreed with the recommendations regarding when to seek specialist advice.

Non albicans Candida species identified

CKS recommends seeking specialist advice if a non-albicans Candida species is identified because the United Kingdom National Guideline on the management of vulvovaginal candidiasis published by the clinical effectiveness group of the British Society of Sexual Health and HIV (BASHH) states that there may be resistance issues with some organisms and longer antifungal treatment courses may be required. In some people with resistant organisms, treatment that can only be initiated by a specialist or is difficult to obtain in primary care may be required [BASHH, 2007h].

General advice on self-management

What general advice can I give about self-management of the current infection?

Advise women about the following personal hygiene measures and how to avoid potential irritants:

Use a soap substitute to clean the vulval area and do not clean the vulval area more than once per day.

Use emollients as moisturisers several times a day to protect the skin. Use an emollient in the bath.

Avoid potential irritants in toiletries, antiseptics, douche, wipes and 'feminine hygiene' products.

Avoid washing underwear in biological washing powder and avoid fabric conditioners.

Probiotics (such as live yoghurts) may be used orally or topically. Although there is no evidence that they are effective, there is no evidence of (or concern about) adverse effects.

Do not advise the use of tea tree oil as there is insufficient evidence to recommend its use.

Avoiding tight-fitting clothing is advised in guidelines but there is no evidence for this advice.

Basis for recommendation

Basis for recommendation

General care

The advice on the general care of vulval skin and the use of emollients is based on expert advice in the guideline 'The management of vulval disorders' published by the Royal College of Obstetricians and Gynaecologists [RCOG, 2011].

Local irritants

CKS found no evidence that local irritants such as soaps and shower gels increase the risk of vulvovaginal candidiasis. However, avoiding local irritants is widely recommended in guidelines [RCGP and BASHH, 2006; BASHH, 2007; RCOG, 2011].

Probiotics

Guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings state that there is currently insufficient evidence to recommend the use of probiotics [FSRH, 2012].

Although there is no good evidence of effectiveness in treating or preventing acute or recurrent vulvovaginal candidiasis, there is no evidence of (or concern about) harm.

Dietary changes

Guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings state that there is currently insufficient evidence to recommend a change in diet. [FSRH, 2012].

Tea tree oil

Guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings that there is currently insufficient evidence to recommend the use of tea tree oil [FSRH, 2012].

Tight-fitting clothes

There is no evidence to suggest that tight-fitting clothing or non-cotton underwear is a risk factor for vulvovaginal candidiasis [Sobel, 2007]. However, avoiding tight-fitting clothing is widely recommended in guidelines [RCGP and BASHH, 2006; BASHH, 2007; RCOG, 2011].

Expert opinion in guidelines developed by the Faculty of Sexual and Reproductive Health Care (FSRH) Clinical Effectiveness Unit (CEU) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings is that there is currently insufficient evidence to recommend advising against wearing tight clothing [FSRH, 2012].

Treating a sexual partner

When should I treat the sexual partner of a woman with vulvovaginal candidiasis?

Treat the sexual partner only if they are symptomatic.

Rarely, the male partner of a woman with vulvovaginal candidiasis has symptoms of balanitis, and this should be treated with a topical or oral antifungal. See the CKS topic on Balanitis for more detailed information.

There is no need to investigate or treat an asymptomatic partner.

Basis for recommendation

Basis for recommendation

There is some evidence that treating an asymptomatic male partner is of little or no benefit in reducing the woman's risk of reinfection/recurrence. Guidelines recommend that asymptomatic male partners not be treated [CDC, 2006; BASHH, 2007; FSRH, 2012].

Contraceptive advice

What advice should I give about contraception?

Advise the woman and her partner that some vaginal/vulval antifungal treatments (such as preparations containing clotrimazole, econazole, fenticonazole, and miconazole) may damage latex contraceptives. Advise abstinence or the use of non-latex barrier methods during use, and for several days after, stopping the antifungal treatment.

Advise women using:

Combined hormonal contraception that:

There is limited evidence on the risk of vulvovaginal candidiasis in users of combined oral contraceptives.

Limited evidence suggests that women with recurrent vulvovaginal candidiasis may benefit from switching to a progestogen-only injectable form of contraception. There is a lack of evidence on the effect of switching to other progestogen-only forms of contraception.

The copper intrauterine device that there is no consistent evidence of an association with vulvovaginal candidiasis.

The levonorgestrel-releasing intrauterine system (LNG-IUS) that users of this method do not have an increased rate of symptomatic infection although they do have an increased presence of Candida.

The combined vaginal ring that there appears to be no effect on the number of pathogenic bacteria or inflammatory cells, although users have been reported to experience more vaginal discharge and irritation compared with combined hormonal contraceptive users.

Basis for recommendation

Basis for recommendation

These recommendations are based on guidelines developed by the Clinical Effectiveness Unit (CEU) of the Faculty of Sexual and Reproductive Healthcare (FSRH) in collaboration with the British Association for Sexual Health and HIV (BASHH) on the management of vaginal discharge in non-genitourinary medicine settings [FSRH, 2012].

Avoiding sex for several days if a latex barrier method is used

This recommendation is pragmatic and based on expert opinion. The guideline does not provide any information about the length of time that abstinence or avoidance of latex condoms should be practised [FSRH, 2012].

Effect of combined hormonal contraception on vulvovaginal candidiasis

It is known that vulvovaginal candidiasis is more common if the vagina is exposed to oestrogen; however, evidence is contradictory about whether combined hormonal contraception increases the risk of vulvovaginal candidiasis [FSRH, 2012].

Progestogen-only injectable contraception

There is evidence from one study that women using a progestogen-only injectable may be less susceptible to developing vulvovaginal candidiasis [FSRH, 2012].

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

Recommended antifungals

Which antifungals are recommended?

Oral or intravaginal imidazole

Which factors influence the decision to use an oral or intravaginal imidazole?

Oral and intravaginal antifungals are equally effective for treating vulvovaginal candidiasis, and choice of therapy may be influenced by a number of factors. See Table 1 for more information.

Table 1 . Factors that may influence the decision to use an oral or intravaginal imidazole for vulvovaginal candidiasis.

Factor Topical imidazoles Oral triazoles
Preference and compliance issues Some women prefer not to use pessaries or products delivered with an intravaginal applicator, which can be painful if there is particularly bad inflammation. Some women find topical cream soothing, however. Simple and painless to use. Available as one or two doses, so few compliance issues.
Time until effect Antifungal cream (applied externally) may relieve symptoms sooner than an intravaginal or oral preparation alone. Oral treatment alone may take slightly longer to take effect.
Adverse effects Vulval inflammation and discharge most commonly reported. More systemic effects such as nausea, headache, and abdominal pain.
Pregnancy Topical clotrimazole and miconazole are suitable during pregnancy and breastfeeding. Contraindicated during pregnancy and breastfeeding.
Contraception Products containing topical imidazoles may damage latex condoms and diaphragms.
Age Intravaginal cream or pessaries are not recommended for pre-pubertal girls. Oral fluconazole is not licensed for use in children aged less than 16 years for the treatment of vaginal candidiasis. However, experts suggest its use may be considered for vaginal candidiasis in girls post-puberty. Itraconazole is not licensed for use in children.
Data from: [MeReC, 2004; BASHH, 2007; Spence, 2010; BNF for Children, 2012]

Initial courses of antifungals

What initial courses of antifungals are recommended?

Oral antifungals:

Oral fluconazole 150 mg (single dose).

Oral itraconazole 200 mg (twice a day for 1 day).

Intravaginal antifungals:

Intravaginal pessaries (such as clotrimazole and econazole pessaries). See Table 1 for more details.

Intravaginal clotrimazole 10% cream (insert 5 g into the vagina as a single dose at night).

Intravaginal fenticonazole 2% cream (insert 5 g into the vagina morning and evening for 3 days).

Topical creams for vulval symptoms

Clotrimazole cream 1%. Use 2–3 times daily.

Clotrimazole cream 2%. Use 2–3 times daily.

Ketoconazole 2% cream. Use 2–3 times daily.

Intravaginal econazole and miconazole can be applied directly to the vulva to manage vulval symptoms.

Table 1 . Initial courses of intravaginal pessaries for vulvovaginal candidiasis.
Preparation Directions
Clotrimazole 500 mg Insert into the vagina once at night
Clotrimazole 200 mg Insert into the vagina once a night for 3 nights
Econazole 150 mg* Insert into the vagina once at night
Econazole 150 mg Insert into the vagina once a night for 3 nights
Miconazole 1200 mg Insert into the vagina once at night
Fenticonazole 600 mg Insert into the vagina once at night
Fenticonazole 200 mg Insert into the vagina once at night for 3 nights
* Formulated for single dose use.
Information from: [BNF 63, 2012]
Basis for recommendation

These recommendations are based on published expert opinion [CDC, 2006; BASHH, 2007].

The doses CKS has recommended for short courses are all licensed.

Extended courses of antifungals

What extended courses of antifungals are recommended?

Oral antifungals:

Fluconazole 100 mg once a day for 7 days.

Itraconazole 200 mg once a day for 7 days.

Intravaginal antifungals:

Intravaginal pessaries (clotrimazole or econazole). See Table 1 for more details.

Intravaginal miconazole 2% cream:

Insert 5 g into the vagina twice a day for 7 days, or

Insert 5 g into the vagina once a day for 14 days.

Intravaginal econazole 1% cream:

Insert 5 g into the vagina at night for 14 nights.

For vulval symptoms, consider prescribing a topical imidazole cream (clotrimazole, miconazole, econazole, or ketoconazole) in addition to an oral or intravaginal antifungal.

Clotrimazole is available as a combination pack containing a 10% vaginal cream and a 2% topical cream (Canesten® Cream Combi) and a combination pack containing a 500 mg vaginal pessary and a 2% topical cream (Canesten® Combi).

Clotrimazole cream may also be bought over-the-counter.

Intravaginal econazole and miconazole may also be applied directly to the vulva to manage vulval symptoms.

Table 1 . Extended courses of intravaginal pessaries recommended for vulvovaginal candidiasis.
Preparation Directions
Clotrimazole 200 mg Insert into the vagina once a night for 6 nights.
Clotrimazole 100 mg Insert into the vagina once a night for 12 nights.
Econazole 150 mg* Insert into the vagina once a night for 6 nights.
* Off-label use
[CDC, 2006; BNF 63, 2012]
Basis for recommendation

These recommendations are based on published expert opinion [CDC, 2006].

The doses CKS has recommended for extended courses are guides, as published reviews and guidelines do not give details of what doses to use. Where possible CKS has recommended preparations that are licensed for extended use.

Nystatin intravaginal cream (Nystan®) is no longer available in the UK.

Which antifungals in breastfeeding

Which antifungals can I prescribe if a woman is breastfeeding?

Prescribe intravaginal clotrimazole or miconazole during breastfeeding as there is extensive experience with their use.

Oral fluconazole and itraconazole are not licensed for use during breastfeeding.

Fluconazole is present in breast milk but probably in amounts too small to be harmful. Ideally it should be taken at night after the last breastfeed.

Itraconazole is not recommended in breastfeeding. The manufacturer states that a very small amount is present in human milk and that benefits should be weighed against risks. If in doubt then the woman should not breastfeed.

Basis for recommendation

These recommendations are based mainly on expert opinion in the textbook Drugs during pregnancy and lactation [Schaefer et al, 2007].

The advice on itraconazole is based on the manufacturer's recommendations in their Summary of Product Characteristics [ABPI Medicines Compendium, 2012c].

Topical imidazoles

Topical products containing imidazoles (clotrimazole, miconazole, fenticonazole, and econazole) may damage latex condoms and diaphragms.

Local mild burning or irritation may occur on application of vaginal imidazole pessaries and creams. Very rarely the woman may find this intolerable and discontinue treatment.

Basis for recommendation

The fatty excipients in topical antifungal products may damage latex condoms and diaphragms [BNF 63, 2012; FSRH, 2012].

Oral fluconazole

The most common adverse effects of fluconazole are gastrointestinal in nature, and include nausea, vomiting, bloating, diarrhoea, and abdominal discomfort.

Fluconazole should not be co-administered with terfenadine. Serious dysrhythmias secondary to prolongation of the QTc interval have been reported in patients receiving other azole antifungals in conjunction with terfenadine.

Discontinue fluconazole if signs or symptoms of liver disease develop. Hepatotoxicity has been reported (very rarely) with fluconazole use.

Basis for recommendation

This information is based on the manufacturer's Summary of Product Characteristics [ABPI Medicines Compendium, 2012b] and a pharmaceutical database [Micromedex, 2007].

Concerns have been raised in the literature that oral fluconazole may cause oral contraceptives to fail [Baxter, 2010]. However, because very few pregnancies have been reported in women taking oral fluconazole and an oral contraceptive, the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC), do not consider additional contraceptive precautions necessary when taking fluconazole [FSRH, 2011].

Oral itraconazole

Oral itraconazole

The most common adverse effects associated with itraconazole are dyspepsia, abdominal pain, nausea, and constipation.

There have been rare reports of liver toxicity.

Advise the person to seek immediate medical attention if symptoms of possible liver toxicity develop, such as anorexia, vomiting, fatigue, abdominal pain, or dark urine [BNF 63, 2012].

Avoid itraconazole in the following people:

People with raised liver enzymes or active liver disease, or people who have a history of developing liver toxicity with other drugs, unless the benefits outweigh the risks.

People with ventricular dysfunction such as congestive cardiac failure or a history of heart failure unless the benefits outweigh the risks [ABPI Medicines Compendium, 2013].

People taking astemizole, pimozide, quinidine or terfenadine, because there is a risk of cardiac arrhythmias.

People taking a statin, as the risk of myopathy is increased [BNF 63, 2012].

Oral contraceptives: There is anecdotal evidence that oral itraconazole may cause oral contraceptive failure, however the Faculty of Sexual and Reproductive Healthcare (FSRH), formerly the Faculty of Family Planning and Reproductive Healthcare (FFPRHC), do not consider additional contraceptive precautions necessary when taking itraconazole [FSRH, 2011].

As a result of rare reports of heart failure, the Committee on the Safety of Medicines (CSM) has advised caution when prescribing itraconazole to patients at high risk of heart failure [CSM, 2001], including:

People receiving high doses and longer treatment courses.

Older people and those with cardiac disease.

People taking negative inotropic drugs (e.g. calcium-channel blockers).

Baseline liver function tests (LFTs) may be considered for people taking short courses of itraconazole. LFTs should be checked if anorexia, jaundice, nausea, vomiting, fatigue, or abdominal pain occur, or if the urine becomes dark during treatment.

Supporting evidence

Evidence

Supporting evidence

Benefits

Evidence on benefits

Antifungal treatments

Evidence on antifungal treatments for acute vulvovaginal candidiasis

Most effective drug

What drugs effectively treat acute uncomplicated vulvovaginal candidiasis?

There is evidence that intravaginal clotrimazole, butoconazole and miconazole, as well as oral itraconazole, are all effective against acute uncomplicated vulvovaginal candidiasis.

Intravaginal butaconazole, clotrimazole, miconazole compared with placebo:

A BMJ Clinical Evidence review [Spence, 2010] found three randomized controlled trials (RCTs) (841 participants, three different drugs, eight different regimens for the active treatments); two of the RCTs were included in an earlier systematic review [Reef et al, 1995].

The BMJ Clinical Evidence review compared outcomes 4–5 weeks after treatment and reported that all three RCTs found statistically significant reduced rates of persistent symptoms. However, there were methodological weaknesses in all the studies.

Oral itraconazole compared with placebo:

A BMJ Clinical Evidence review [Spence, 2010] found one RCT (90 participants, three interventions), which had been included in a Cochrane systematic review [Nurbhai et al, 2007]

Oral itraconazole significantly reduced the proportion of women with persistent symptoms at 1 week after treatment, compared with placebo.

Intravaginal nystatin compared with placebo:

A BMJ Clinical Evidence review [Spence, 2010] found one RCT (50 participants). Intravaginal nystatin (500,000 IU twice daily for 14 days) significantly reduced the proportion of women with a symptomatic response categorized as 'poor'.

Most effective regimen

Which is the most effective regimen for treating acute uncomplicated vulvovaginal candidiasis?

Evidence from RCTs shows oral triazoles (fluconazole and itraconazole) to be as effective as vaginal imidazoles for the treatment of vulvovaginal candidiasis.

Comparison between intravaginal imidazoles: no clinically important differences were found when butoconazole, clotrimazole, econazole, fenticonazole, flutrimazole, isoconazole, miconazole, sertaconazole, and terconazole were compared in RCTs of various combinations of intravaginal treatments for vulvovaginal candidiasis.

A BMJ Clinical Evidence review [Spence, 2010], found 22 RCTs, nine of which were included in an earlier systematic review, [Reef et al, 1995].

The BMJ Clinical Evidence review reported outcomes (rates of persistent symptoms and laboratory evidence of infection) 7–35 days after treatment, and reported that no RCT found statistically significant differences between drugs. However, there were methodological weaknesses in all the studies, and many were statistically underpowered to conclude that different treatments are similarly effective.

Comparison between different doses and durations of intravaginal imidazoles: no clinically important differences were found when butoconazole (1% or 2% for 3 or 6 days), clotrimazole (100 mg or 200 mg pessary for 3, 6, 7, or 14 days), miconazole (2% for 6 or 14 days), and terconazole (240 mg once, or 80 mg daily for 3 days) were compared in RCTs of various combinations of intravaginal treatments for vulvovaginal candidiasis.

A BMJ Clinical Evidence review [Spence, 2010], found six RCTs, five of which were included in an earlier systematic review [Reef et al, 1995].

The trials found no consistent difference in outcome between treatment regimens. However, the trials included too few participants to confidently conclude that the different regimens are similarly effective.

Comparison between intravaginal imidazoles and oral triazoles: no clinically important differences in effectiveness were found when clotrimazole, econazole, miconazole, and terconazole (intravaginal imidazoles) were compared with fluconazole or itraconazole (oral triazoles) for treating vulvovaginal candidiasis.

A Cochrane systematic review and meta-analysis compared oral imidazoles with intravaginal imidazoles for treating vulvovaginal candidiasis [Nurbhai et al, 2007].

The review found no evidence for a clinically important difference in effectiveness between intravaginal and oral treatments for vulvovaginal candidiasis in terms of clinical or laboratory cure in the short term (5–15 days) or the long term (2–12 weeks). Subgroup and sensitivity analyses did not alter the conclusions.

At short-term follow-up (5–16 days), clinical cure was achieved in 73% of women using intravaginal treatment and 74% of women using oral treatment (OR 0.95, 95% CI 0.75 to 1.17).

At short-term follow-up, mycological cure was achieved in 80% of women using intravaginal treatment and 83% of women using oral treatment (OR 1.15, 95% CI 0.94 to 1.42).

At long-term follow-up (4–12 weeks), clinical cure was achieved in 76% of women using intravaginal treatment and 80% of women using oral treatment (OR 1.07, 95% CI 0.82 to 1.41).

At long-term follow-up, mycological cure was achieved in 66% of women using intravaginal treatment and 72% of women using oral treatment (OR 1.29, 95% CI 1.05 to 1.60).

Comparison between oral triazoles:

A BMJ Clinical Evidence review found one systematic review (six RCTs, 1092 women) which compared oral fluconazole and oral itraconazole as treatments for vulvovaginal candidiasis [Spence, 2010].

There was no statistically significant difference between the cure rates with fluconazole and itraconazole at 10 days and 8 weeks follow up.

Response to treatment

How quickly do women respond to treatment for vulvovaginal candidiasis?

There is limited evidence from one open-label parallel study that the onset of relief from symptoms is more rapid with intravaginal treatment compared with oral treatment.

Rate of response to treatment for acute vulvovaginal candidiasis:

One randomized, open-label, parallel study included 181 women with moderate to severe symptoms of acute vulvovaginal candidiasis [Seidman and Skokos, 2005]. More than 50% of women felt the onset of relief within 24 hours.

Onset of relief was more rapid with intravaginal treatment than with oral treatment (see Table 1).

Longer-term outcomes were similar for intravaginal and oral treatments (data not shown in the table).

Table 1 . Time to respond to treatment for acute vulvovaginal candidiasis.
Outcome measure Women treated with: p-value
Butoconazole (intravaginal) Fluconazole (oral)
Median time to first relief of symptoms 17.5 hours 22.9 hours < 0.001
Time at which 75% women had first relief 24.5 hours 46.3 hours < 0.048
Proportion of women with first relief of symptoms by 12 hours 44.4% 29.1% 0.044
Proportion of women with first relief of symptoms by 24 hours 72.8% 55.7% 0.024
Data from: [Seidman and Skokos, 2005]

Strategies for recurrent candidiasis

What strategies are effective for recurrent vulvovaginal candidiasis?

Six randomized controlled trials (RCTs) found that maintenance therapy with weekly oral fluconazole, or monthly oral itraconazole, or monthly intravaginal clotrimazole reduced rates of recurrence of vulvovaginal candidiasis while the treatment was being taken. The level of protection fell on stopping maintenance treatment, but for oral fluconazole protection was still clinically and statistically significant 6 months later. One small crossover study found that women greatly preferred 'as required' treatment with intravaginal clotrimazole to maintenance therapy with intravaginal clotrimazole, although they experienced more recurrences while on the 'treat as required' strategy. Neither development of resistant strains of Candida albicans, nor superinfection with C. glabrata seem to be problems with maintenance therapy.

Oral fluconazole for maintenance therapy:

Oral fluconazole compared with placebo. A BMJ Clinical Evidence review, [Spence, 2010], found one RCT (387 participants) which assessed fluconazole maintenance therapy for recurrent vulvovaginal candidiasis [Sobel et al, 2004]. The acute presenting event was treated with oral fluconazole, which induced clinical remission in 91% of participants. For the maintenance phase, women who responded to treatment of acute vulvovaginal candidiasis were randomly assigned to either oral fluconazole 150 mg or placebo, every week for 6 months. Participants were followed up for a further 6 months.

At 6, 9, and 12 months, significantly more fluconazole-treated women remained free of vulvovaginal candidiasis. Details are shown in Table 1.

Median time to recurrence was significantly longer in women treated with fluconazole: 10.2 months compared with 4.0 months for the placebo group (p < 0.001).

During the course of the trial, isolates of Candida albicans did not develop resistance to fluconazole, and superinfection with C. glabrata was not observed.

Table 1 . Oral fluconazole compared with placebo for preventing recurrent vulvovaginal candidiasis.
Time of follow up Proportion remaining disease free p-value
Oral fluconazole group Placebo group
6 months (on treatment) 90.8% 35.9% < 0.001
9 months (off treatment) 73.2% 27.8% < 0.001
12 months (off treatment) 42.9% 21.9% < 0.001
Data from: [Sobel et al, 2004]

Oral itraconazole for maintenance therapy:

Oral itraconazole compared with placebo. A BMJ Clinical Evidence review [Spence, 2010] found one placebo-controlled randomized trial (114 participants) of 6 months' maintenance therapy (itraconazole 400 mg monthly) for recurrent vulvovaginal candidiasis [Spinillo et al, 1997].

Proportion of women with recurrences at 6 months, itraconazole group and placebo group: 36.4% vs. 64.2% (p < 0.001).

Proportion of women with recurrences at 12 months, itraconazole group and placebo group: 61.1% vs. 71.2% (p = 0.83).

Mean time to recurrence, itraconazole group and placebo group: 149 days and 120 days (p = 0.003).

Oral itraconazole compared with intravaginal clotrimazole. A small trial (44 women) comparing oral itraconazole (200 mg twice weekly) with intravaginal clotrimazole (200 mg twice weekly) was found by a BMJ Clinical Evidence review [Spence, 2010]. The results (more recurrences in the oral itraconazole group) are difficult to interpret because of methodological weaknesses (statistically underpowered, not blinded, unbalanced withdrawals from the study).

Intravaginal clotrimazole for maintenance therapy:

Intravaginal clotrimazole compared with placebo. A BMJ Clinical Evidence review [Spence, 2010], found two placebo controlled RCTs (89 participants) of intravaginal clotrimazole (500 mg monthly) as maintenance therapy for recurrent vulvovaginal candidiasis.

Proportion of women with recurrences at 6 months, clotrimazole group and placebo group, first RCT: 30% vs. 79% (p < 0.001); second RCT: 53% vs. 67% (p > 0.05).

Intravaginal clotrimazole maintenance therapy (regular prophylaxis) compared with treatment 'as required':

A BMJ Clinical Evidence review [Spence, 2010], found one crossover RCT (23 participants) which compared maintenance therapy with 'as required' treatment for women with recurrent vulvovaginal candidiasis [Fong, 1994]. Maintenance therapy was intravaginal clotrimazole 500 mg used monthly. 'As required' treatment was intravaginal clotrimazole used when symptoms recurred.

Average number of episodes per woman over a 6-month period, while on maintenance therapy and while on 'as required' treatment: 2.2 vs. 3.7 (p = 0.05).

Proportion of women who preferred maintenance therapy or 'as required' treatment: 17% vs. 74% (p = 0.001).

Mean number of clotrimazole doses used during the prophylactic period and during the empiric self-treatment period: 7.3 vs. 3.6 (p < 0.001).

Oral ketoconazole:

An observational study of oral ketoconazole therapy in 40 women who suffered from recurrent vulvovaginal candidiasis reported that, for half the women, symptoms were relieved within three days, and that two-thirds of the women remained symptom free for a period of at least a month. About 90% of women preferred oral to topical therapy [Kovacs et al, 1990].

Treatments during pregnancy

What treatments are effective for vulvovaginal candidiasis during pregnancy?

A Cochrane systematic review of 10 randomized controlled trials (RCTs) provides evidence that treatment with topical imidazoles is more effective than topical nystatin in the treatment of pregnant women with vulvovaginal candidiasis, and that longer courses (7 days) cured more than 90% of women whereas standard (4 days) courses only cured about half the cases.

A Cochrane systematic review (search date: March 2001) of 10 trials assessed the effectiveness of miconazole, clotrimazole, econazole, terconazole, and hydrargaphen for the treatment of vulvovaginal candidiasis in pregnant women [Young and Jewell, 2001]. A further literature search for this Cochrane systematic review in October 2009 did not find any new evidence to necessitate a change to conclusions. The main results were:

Imidazole drugs were more effective than nystatin (five trials, odds ratio 0.21, 95% CI 0.16 to 0.29).

Clotrimazole was more effective than placebo (one trial, odds ratio 0.14, 95% CI 0.06 to 0.31).

Terconazole was as effective as clotrimazole.

Single-dose treatment was as effective as treatment for 3–4 days.

Treatment for 7 days was as effective as treatment for 14 days (two trials).

Treatment for 7 days was more effective than treatment for 4 days (two trials with 81 women).

This review did not report safety outcome data.

Management of treatment failure

What treatments are effective for vulvovaginal candidiasis that has failed to respond to usual treatment?

CKS found no relevant trials.

Treating male sexual partners

Should male sexual partners of women with acute or recurrent vulvovaginal candidiasis be treated?

There is some evidence that treating an asymptomatic male partner is of little or no benefit in reducing the woman's risk of reinfection/recurrence.

An RCT (40 couples) assessed the benefits of treating the male partners of women with acute vulvovaginal candidiasis [Calderon-Marquez, 1987]. The men were randomized to receive oral itraconazole 100 mg daily for 5 days or placebo. The women were treated with oral itraconazole 100 mg daily for 5 days.

Proportion of women with persistent symptoms after 30 days:

Male partners treated with itraconazole compared with male partners who received placebo: 2 of 19 (11%) vs. 4 of 18 (22%), (odds ratio 0.43, 95% CI 0.08 to 2.43).

The results were not statistically significant.

An RCT (42 couples) assessed the benefits of treating the male partners of women with acute vulvovaginal candidiasis [Buch and Skytte Christensen, 1982]. The men were randomized to receive topical natamycin for 10 days or placebo. The women were treated with topical natamycin for 10 days.

Proportion of women with symptoms after 8 days:

Male partners treated with topical natamycin compared with male partners who received placebo: 1 of 16 (6%) vs. 2 of 17 (12%), p > 0.05.

Proportion of women who had recurrent symptoms within 39 days:

Male partners treated with topical natamycin compared with male partners who received placebo: 6 of 16 (37%) vs. 6 of 17 (35%), p > 0.05.

An RCT (117 couples) assessed the benefits of treating the male partners of women with acute vulvovaginal candidiasis [Bisschop et al, 1986]. The men were randomized to receive oral ketoconazole 200 mg twice daily for 3 days or placebo. The women were treated with ketoconazole 200 mg taken once, twice, or three times daily for 3 days.

Proportion of women with symptoms after 1 week:

Male partners treated with oral ketoconazole compared with male partners who received placebo: 48 of 57 (84%) vs. 53 of 60 (88%), p > 0.05.

Proportion of women with recurrent symptoms within 4 weeks:

Male partners treated with oral ketoconazole compared with male partners who received placebo: 13 of 35 (27%) vs. 19 of 35 (36%), p > 0.05.

An RCT (54 couples) assessed the benefits of treating the male partners of women with acute vulvovaginal candidiasis [Fong, 1992]. The men were randomized to receive oral ketoconazole 200 mg daily for 5 days or placebo. The women were treated with ketoconazole 400 mg daily for 7 days.

Proportion of women with recurrence within 6 months:

Male partners treated with oral ketoconazole compared with male partners who received placebo: 17 of 26 (65%) vs. 20 of 28 (71%) (95% CI –19% to 31%).

Proportion of women with recurrence within 12 months:

Male partners treated with oral ketoconazole compared with male partners who received placebo: 22 of 26 (85%) vs. 23 of 28 (82%) (95% CI –23% to 17%).

An RCT (144 couples) assessed the benefits of treating the male partners of women with acute vulvovaginal candidiasis [Shihadeh and Nawafleh, 2000]. The men were randomized to receive oral ketoconazole 400 mg daily for 7 days or placebo. The women were treated with ketoconazole 400 mg daily for 7 days.

Proportion of women assessed as cured after 7 days:

Male partners treated with oral ketoconazole compared with male partners who received placebo: 57 of 72 (79%) vs. 53 of 72 (74%), p > 0.05.

Proportion of women with recurrence within 4 weeks:

Male partners treated with oral ketoconazole compared with male partners who received placebo: 28 of 53 (53%) vs. 35 of 57 (61%), p > 0.05.

Probiotics

Evidence on probiotics for treating or preventing vulvovaginal candidiasis

Effectiveness of probiotics

Are probiotics an effective treatment for acute vulvovaginal candidiasis?

There is inconsistent evidence about whether probiotics might effectively treat vulvovaginal candidiasis.

Evidence from laboratory experiments, observational studies with clinical outcomes, and randomized controlled trials (RCTs) with non-clinical outcomes (such as vaginal microbial flora) inconsistently suggests that probiotics administered orally or intravaginally might effectively treat vulvovaginal candidiasis [Falagas et al, 2006].

Prevention

Can probiotics prevent vulvovaginal candidiasis?

There is no good evidence of the effectiveness of probiotics in treating or preventing acute or recurrent vulvovaginal candidiasis. However there is no evidence of (or concern about) harm.

A BMJ Clinical Evidence review [Spence, 2010] found one systematic review (2002) which identified no clinical trials. However one additional RCT was found that involved 55 women who all took 150 mg of oral fluconazole at the start of the trial. The women were then randomized to take either oral yoghurt containing lactobacillus or placebo for 1 month. It was concluded that lactobacillus containing yoghurt may be effective at reducing the rate of thrush symptoms associated with vaginal discharge (p = 0.03) and also at lowering the rate of yeast detected by culture at one month (p = 0.01). There were no reports of harm other than oral yoghurt may cause gastrointestinal disturbance in women with lactose intolerance.

Probiotics may not prevent antibiotic-induced vulvovaginal candidiasis:

One RCT (278 women entered, 235 completed) studied Lactobacillus preparations taken orally or vaginally, or both, while participants were using antibiotics and for the following 4 days.

Compared with placebo, the odds ratio for developing post-antibiotic vulvovaginitis with oral lactobacillus was 1.06 (95% CI 0.58 to 1.94) and with vaginal lactobacillus 1.38 (95% CI 0.75 to 2.54) [Pirotta et al, 2004].

Probiotics may reduce the risk of vulvovaginal candidiasis in women with HIV:

One placebo-controlled RCT (164 participants, median follow up 21 months) assessed the effectiveness of weekly intravaginal application of Lactobacillus acidophilus or weekly intravaginal application of clotrimazole tablets in preventing vulvovaginal candidiasis in HIV-positive women. Although the results favoured use of the probiotic, they were not statistically significant, and may not be clinically important.

The relative risk of a new episode of vulvovaginal candidiasis was 0.5 (95% CI 0.2 to 1.1) for women using Lactobacillus acidophilus, and 0.4 (95% CI 0.2 to 0.9) for women using clotrimazole.

Compared with placebo, the time to the first episode of vulvovaginal candidiasis for women using Lactobacillus acidophilus was longer (p = 0.09, log rank test) [Williams et al, 2001].

Probiotics may reduce the risk of vulvovaginal candidiasis in women with recurrent vulvovaginal candidiasis:

A crossover RCT (33 women entered, 13 completed) studied the effects of including lactobacillus yoghurt in the diet of women with recurrent vulvovaginal candidiasis.

The mean number of episodes of vulvovaginal candidiasis was 0.38 during the 6 months with yoghurt in the diet and 2.54 during the 6 months with no yoghurt in the diet (p = 0.001) [Hilton et al, 1992].

Harms

Evidence on harms

Harms caused by treatment

Evidence on harms caused by treatments for vulvovaginal candidiasis

Vulval burning and vaginal discharge are more common with intravaginal imidazoles, whilst nausea, headache, and abdominal pain are more common with oral imidazoles. This evidence is from over 20 randomized controlled trials (RCTs). No serious harms were reported by the studies. However, unless they are extremely large or specifically powered, RCTs generally have too few participants to detect rare adverse events.

Intravaginal medicines used to treat vulvovaginal candidiasis:

Intravaginal medicines used to treat vulvovaginal candidiasis may damage latex condoms and diaphragms [Meyboom et al, 1995].

A BMJ Clinical Evidence review found a laboratory study of the effect of intravaginal miconazole on latex condoms. After an hour's incubation with intravaginal miconazole, the bursting pressure and the bursting volume of latex condoms were reduced by about 40%. The authors speculated that fatty excipients in the product might damage condoms [Spence, 2010].

Intravaginal imidazoles:

A BMJ Clinical Evidence review found that common adverse effects were vulval burning or irritation, and headache [Spence, 2010].

Intravaginal nystatin:

A BMJ Clinical Evidence review found one RCT that included 50 women and reported that there were no adverse effects [Spence, 2010].

Oral fluconazole and itraconazole:

A BMJ Clinical Evidence review found that common adverse effects were gastrointestinal disturbances, nausea, pelvic pain, insomnia, anxiety, and rash. These were similar with fluconazole and itraconazole [Spence, 2010]:

Nausea, headache, and abdominal pain are more common than with intravaginal imidazoles.

Vulval burning and vaginal discharge are less common than with intravaginal imidazoles.

Intravaginal imidazoles compared with oral imidazoles:

A BMJ Clinical Evidence review found one systematic review that compared oral fluconazole and itraconazole with intravaginal imidazoles [Spence, 2010]. It was found that:

There was no difference between oral fluconazole and itraconazole in reducing persistent symptoms at short-term follow up treatment.

Oral treatment was more effective than intravaginal treatment at long-term follow up at reducing persistent symptoms.

Intravaginal boric acid:

One RCT reported that intravaginal boric acid can cause skin irritation, but made no comparison with intravaginal nystatin [Spence, 2010].

Long-term maintenance therapy to prevent recurrent vulvovaginal candidiasis:

Long-term maintenance therapy has not been associated with serious harms. One RCT of oral fluconazole used for maintenance therapy reported no serious adverse clinical effects, that resistant strains of Candida albicans were not found, and that superinfection with C. glabrata did not occur [Spence, 2010].

Resistance of yeasts to antifungals

Evidence on resistance of yeasts to antifungal treatments for vulvovaginal candidiasis

There is evidence to suggest that intravaginal nystatin is more effective than topical or oral azoles against Candida glabrata and other non-albicans Candida species.

Laboratory studies show that:

In vitro resistance to azole antifungals is common (see Table 1).

There may be cross-resistance between different azoles, but not between azoles and nystatin [Sojakova et al, 2004].

In vitro resistance to azoles may be more common than resistance to nystatin (see Table 1).

CKS found no studies assessing the relationship between in vitro resistance and clinical resistance.

Table 1 . Resistance (in vitro) of Candida species to antifungal drugs.
Antifungal All Candida isolates C. albicans
Fluconazole 6% [Bellitti et al, 2002] 13% [Sojakova et al, 2004] 16.7% [Verghese et al, 2001] 13% [Saporiti et al, 2001]
Itraconazole 18.5% [Sojakova et al, 2004] 45% [Verghese et al, 2001]
Econozole 27% [Bellitti et al, 2002] 7% [Perera and Clayton, 1994]
Miconazole 42% [Perera and Clayton, 1994]
Clotrimazole 13% [Perera and Clayton, 1994] 50% [al-Rawi and Kavanagh, 1999]
Ketoconazole 26% [Perera and Clayton, 1994]
Nystatin 0% [Bellitti et al, 2002] 9.5% [Verghese et al, 2001] 8% [Perera and Clayton, 1994]

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on primary care management of candida - female genital.

Search dates

January 2007 – July 2012

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

exp Candidiasis, Vulvovaginal/, candida.tw., candidal.tw., candidiosis.tw., candidiasis.tw., thrush.tw., exp Vagina/, exp Vulva/, vagina.tw., vaginal.tw., vulvo$.tw., vulva.tw., vulval.tw.

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSh subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Topic specific literature search sources

Faculty of Sexual and Reproductive Healthcare

Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Bandolier

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

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