e e VOLUME 14 NUMBER 4 An update on vulvovaginal candidiasis (thrush) SUMMARY This Bulletin outlines the correct diagnosis and treatment of vulvovaginal candidiasis (thrush) by patients and by health care professionals. It also discusses some of the commonly held but often incorrect beliefs about the infection. • Thrush is the second most common vaginal infection after bacterial vaginosis and up to 75% of women suffer an episode at some point in their life. • Some women suffer from recurrent episodes of thrush and can suffer psychosexual problems and depression as a consequence. • It would seem wise to prescribe the most cost-effective product that is acceptable to the individual. • Women sometimes restrict their lives unnecessarily by following preventive measures that have little evidence to support them or because they feel embarrassed that they have thrush. It is important to provide them with informed reassurance. Although it is sometimes dismissed as a minor infection, thrush is the second most common vaginal infection after bacterial vaginosis.1 Up to 75% of women suffer an episode of thrush at some point in their life and about half of these have more than one episode.2 Candida albicans is the usual cause of thrush and is isolated in 80 to 95% of swabs taken from women with the infection.2 However, many women with no symptoms or clinical signs of thrush are colonised with candida and it could be part of the normal vaginal flora.2 It is likely, therefore, that changes to the vaginal environment are required for symptoms to develop but it is not known what these are.2 The second most common species to cause thrush is C. glabrata, which occurs in about 5% of infections. C. glabrata tends to be more resistant to antifungal treatment than C. albicans and is harder to treat.2 Women of childbearing age are most likely to develop thrush, because oestrogens enhance the proliferation, germination and adherence of C. albicans to the vaginal epithelium.3 Thrush is more common in women with diabetes mellitus, and in women who have recently taken broad-spectrum antibiotics.2 This could be because high glucose levels may increase adhesion of C. albicans to the vaginal epithelium, and broad spectrum antibiotics eliminate the normal protective bacterial flora.1,4 Pregnant women are particularly susceptible to candida infection, because increased levels of reproductive hormones favour the growth of yeasts.1 However, there is no evidence that thrush harms the fetus.5 Thrush is thought to be less common in postmenopausal women but a diagnosis of candidiasis in such women should not be discounted. Symptomatic infection in postmenopausal women is usually associated with uncontrolled diabetes mellitus, hormone replacement therapy, antibiotic use, severe underlying disease, immunosuppressive agents or tamoxifen.3 Diagnosis of thrush Patients and GPs often attribute symptoms such as pruritus and vaginal discharge to thrush and a diagnosis is made without physical examination.2 However, bacterial vaginosis is a more common infection, can have similar symptoms and can occur at the same time as thrush in up to 10% of cases.2,6 Guidelines from a working group of the British Society for Medical Mycology state that swabs for fungal culture need not be taken on a first visit if typical signs and symptoms of thrush are present, unless the patient could have a sexually transmitted disease. 2 However, if symptoms persist despite empirical antifungal treatment, the patient should be examined and mycological and microbiological investigations made (e.g. vaginal specimen culture and/or vaginal pH test).2,6 Bacterial vaginosis is more common than thrush and can have similar symptoms Classification of thrush Thrush is classified in a number of ways in clinical trials, which can be confusing, Date of preparation: January 2004 This MeReC Publication is produced by the NHS for the NHS MeReC Bulletin Volume 14, Number 4 13 An update on vulvovaginal candidiasis (thrush) especially as the US and UK use different definitions. Various categories of thrush are explained below. Single-dose oral antifungal treatment is as effective as multiple-dose topical treatments of varying length In the UK, thrush is considered as being either acute or recurrent (i.e. four or more episodes of symptomatic thrush each year), in accordance with a 1999 guideline on thrush management put together by the Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases.7 However, some studies also refer to chronic thrush (meaning continuous or recurrent infection). A more recent US guideline classifies thrush into uncomplicated or complicated infection. It defines uncomplicated thrush as being infection that is mild-to-moderate, infrequent and likely to be caused by C. albicans, and that responds well to topical or oral antifungal treatment.8 It subdivides complicated thrush into recurrent infection (defined as above), severe infection, non-albicans infection, infection in immunocompromised women (e.g. those with HIV or women who are taking corticosteroids) and infection during pregnancy.8 Severe infection gives rise to fissures and extensive erythema and oedema of the vulva. It does not respond well to short courses of treatment.8 Which treatment? There is conflicting evidence about the efficacy of lactobacillus preparations and live yoghurt Uncomplicated infection Five imidazole derivatives are available for treatment of thrush in a number of topical formulations (i.e. pessaries and intravaginal creams) — clotrimazole, econazole, fenticonazole, ketoconazole and miconazole. Topical nystatin can also be used but has a 14-day course of treatment and can stain clothes yellow, which may reduce acceptability. 2,9 However, it can be useful in women whose thrush has not responded to imidazoles.2 In addition, some preparations of clotrimazole, miconazole and povidone-iodine are licensed for treatment of mixed (i.e. bacterial and fungal) infections. Patients should apply a topical cream to the vulva as well as inserting intravaginal cream or pessaries into the vagina, because this is another area that becomes colonised by candida.10 Itraconazole and fluconazole are licensed for oral treatment of candidiasis, and oral ketoconazole can be given but has been associated rarely with fulminant hepatitis. Therefore, it is only used in patients with thrush that has not responded to other treatments.6,11 A Cochrane review of 17 randomised controlled trials (RCTs) reporting 19 comparisons of oral versus intravaginal antifungals, states that topical imidazoles and oral antifungals are equally effective at both long- and short-term follow-up. 12 It adds that single-dose oral antifungal treatment is as effective as multipledose topical treatments of varying length, except in pregnant women, who require multiple doses 14 of topical treatment. At short-term follow-up, 80% of women were cured clinically by either oral or intravaginal treatment. At long-term follow-up, 83% of women were cured clinically by oral treatment and 82% by intravaginal antifungals. Short term follow-up was defined as five to 15 days after a course of treatment and long term as two to 12 weeks after a course of treatment. The review also concludes that there is no statistically significant difference between mycological cures achieved with oral and intravaginal treatment at short- or long-term follow-up. At short-term follow-up, over 80% of women achieved mycological cure with either route of administration but, long term, the figures decreased to 72% for oral treatment and 66% for intravaginal treatment. The review comments that the 20% of women who were not cured may not have had candida infection or may have been infected with a non-albicans strain. It adds that the decrease in mycological cure long term might be a result of regrowth of candida as part of the vaginal flora. The decision to prescribe or recommend for purchase an antifungal treatment should be based on efficacy, safety, cost and patient preference. Oral treatment is more expensive than topical treatment and may cause more serious systemic adverse effects.12 Nevertheless, the Cochrane review recommends it as the treatment of choice in non-pregnant women, although it adds that prescribers and patients who treat themselves should consider whether the higher cost of oral treatment is worth the gain in convenience and patient preference, as both are equally effective. Patients have different reasons for preferring a certain route of treatment. Some women prefer to take a capsule rather than using pessaries and creams, because insertion can be painful if the vulva is very inflamed.2 However, others might find a cream soothing.10 Therefore, it would seem wise to prescribe the most inexpensive product that is acceptable to the patient. It is important to remember that if a patient is prescribed topical or oral treatment and also cream to apply externally, they may have to pay two prescription charges. Symptoms should begin to resolve once treatment begins but some women find that vulval itching and burning disappear more quickly if an antifungal cream is applied to the vulva in addition to oral or intravaginal treatment.9 If symptoms do not respond within seven to 14 days, the patient should return to her GP.13–15 Some women use tampons impregnated with tea tree oil to treat thrush but this can cause severe allergic reactions.16 Other measures include inserting lactobacillus-containing preparations into the vagina, and eating live yoghurt.16 Lactobacillus preparations sold for MeReC Bulletin Volume 14, Number 4 An update on vulvovaginal candidiasis (thrush) correcting the vaginal flora may not always contain the species most commonly found in a healthy vagina and their usefulness is questionable. Similarly, there is conflicting evidence about the usefulness of yoghurt at preventing infection.16 However, anecdotally, some women say they derive benefit from both types of preparation.2,16 Complicated infection Women with chronic or recurrent thrush seldom have recognisable precipitating factors and the condition can lead to psychosexual problems (e.g. feeling unclean or not wanting to have sex) and depression, which should be taken into account as part of diagnosis and treatment.2,6 Physical examination, investigation for underlying disease and mycological investigation are recommended.2 Recurrent and severe infection Recurrent and severe infection are treated in a similar way.8 PRODIGY recommends an initial one- to twoweek course of topical clotrimazole, or oral itraconazole or fluconazole, followed by oncea-week (twice a week for itraconazole) maintenance treatment for six months.6 This is an unlicensed use of these drugs in the UK. After symptoms have been suppressed for three to six months, prophylaxis can be discontinued and the woman reassessed.2 However, at least half of women suffer a recurrence once the drugs are stopped and some women may need maintenance treatment for years.6 The US guideline recommends using a seven- to 14-day course of topical treatment or a 150mg oral fluconazole dose with a second one given three days later (this is an unlicensed use in the UK).8 Anecdotal reports suggest that some women with recurrent thrush develop symptoms around the time of their period. Therefore, using treatment just before, during or immediately after menstruation may improve the outcome in recurrent thrush.6 Non-albicans infection Women with nonalbicans infections are often referred to a specialist2 and drug regimens used include topical nystatin or a seven- to 14-day course of a topical imidazole.6,8 If the infection is recurrent, boric acid in a gelatine capsule can be inserted vaginally, although case reports have associated this treatment with systemic boron toxicity.8,11 Flucytosine has been used but the long-term safety of this drug is not known.8 A maintenance regimen of nystatin pessaries (100,000 units daily) can also be used. 8 However, none of these treatment regimens are licensed in the UK. Immunocompromised patients Women who are immunocompromised may need seven- to 14-day courses of topical treatment.8 Pregnancy All topical antifungal products can be used during pregnancy but oral treatment should not be given to either pregnant women or to nursing mothers.13–15 A recent Cochrane MeReC Bulletin Volume 14, Number 4 review of 10 RCTs in pregnant women with thrush concluded that topical imidazoles were more effective than topical nystatin for treating symptoms but added that a seven-day course might be necessary in pregnant women.5 PRODIGY recommends topical clotrimazole as the drug of choice, because it is supported by the most data in pregnant women, followed by topical miconazole and econazole.6 Applicators can be used to insert topical preparations into the vagina during pregnancy but expectant mothers may prefer to insert pessaries using a finger.6 What about over-the-counter products? Many treatments for thrush can be bought over the counter (OTC). When OTC antifungals were first made available, two concerns were expressed — that women might misdiagnose their symptoms and that there would be an increase in drug resistance in candida species. Have these concerns been realised? Misdiagnosis There is some evidence that women do misdiagnose thrush. The results of a US study of 95 women who purchased OTC antifungal products for presumed thrush showed that only one-third had the infection.17 Of the rest, 19% had bacterial vaginosis, 21% had mixed vaginosis, 14% had no infection, 11% had other diagnoses and 2% had trichomoniasis. Women with a previous physician-confirmed diagnosis of thrush and women who read the label on the product packaging were no more accurate than other women at self-diagnosis. Oral treatment should not be given to pregnant women or nursing mothers A Finnish study showed that out of 299 women who purchased intravaginal antifungal drugs, 44% were using drug treatment against recommendations.18 Of these, 14% had never had their thrush diagnosed by a physician, 30% had already used two or more treatments over the past year without visiting a physician, 3% were pregnant and had not been recommended the treatment by a health care professional and two users were under 16 years of age. Panel 1: When to refer a woman to her GP13,19 A patient should see her GP if she: • Is a first-time sufferer whose thrush has not previously been diagnosed by a physician • Is younger than 16 or older than 60 years of age • Has had at least two episodes of thrush in the past six months but has not consulted her GP about the condition for more than a year • Has a previous history of sexually transmitted disease or has been exposed to a partner with one • Is or might be pregnant • Has foul-smelling vaginal discharge • Has abnormal or irregular vaginal bleeding or blood-stained discharge • Has pain in the lower abdomen • Has experienced an adverse reaction to antifungal products • Has dysuria — pain on urination is rare with thrush, although external dysuria can occur • Has vulval or vaginal sores, ulcers or blisters. These are more commonly associated with herpes infections • Experiences no improvement after seven days’ empirical treatment. 15 An update on vulvovaginal candidiasis (thrush) Women need information about all vaginal infections and their symptoms, to help them judge whether or not they have thrush. Health care professionals should help prevent incorrect self-diagnosis or continual use of OTC medications by providing this information. The situations in which a woman should see their GP are listed in Panel 1. Resistance There is no surveillance network for monitoring resistance to antifungals in the UK.20 Fears that making imidazole treatments available OTC would result in an increase in resistant strains of C. albicans do not seem to have been realised.20 However, strains that are inherently less sensitive to the drugs (e.g. C. glabrata) might be on the increase.20 The reason why some women infected with highly susceptible strains of C. albicans occasionally do not respond clinically, and why many more improve clinically but remain colonised with C. albicans, is not known. However, it might be because imidazoles are fungistatic rather than fungicidal.21 Conclusion The trigger for most cases of thrush is not known. This can be frustrating both for women and for health care professionals. Women with thrush often treat themselves, either with OTC products or with alternative therapies but may not make a correct diagnosis. It is therefore important that health care professionals help women to obtain appropriate treatment by providing them with information and advice about all vaginal infections and the various formulations available for treatment of thrush. In addition, health care professionals should know when to refer patients for further investigation. The evidence for some commonly-held beliefs about thrush Resources Although our understanding of thrush has improved, there are still myths that some women and health care professionals believe about the disease. It is important to discuss with women the evidence (or lack of it) for these, to prevent them from feeling embarrassed about the condition or from unnecessarily restricting their lives. PRODIGY has produced a patient information leaflet about thrush, which can be downloaded from its website: http://www.prodigy.nhs.uk. Tight-fitting clothing can precipitate an attack The evidence that clothing can trigger an attack of thrush is controversial, as study results have been conflicting. However, women who are frequently affected by thrush may prefer to wear loose cotton underwear.2,16 Sanitary towels are more likely to bring on an attack than tampons Study results have been inconclusive about whether women who use sanitary towels are more likely to have episodes of thrush than those who use tampons.6,16 Reducing sugar intake prevents thrush Some women with recurrent thrush decrease their intake of sugary foods in an attempt to reduce the number of episodes of the condition. However, there is currently not enough evidence to support this practice.16 Infection is spread from the rectum Thrush is no longer thought to be spread from the rectum.1 Several studies have shown that candidiasis is not always found in the rectum of thrush sufferers, even when vaginal infection is present. Also, reducing intestinal colonisation with C. albicans does not prevent vaginal recurrence.2 Relapse may occur because of incomplete eradication of organisms after treatment. As a general health precaution, it seems wise to advise women to wipe from front to back after defaecation and to avoid vaginal intercourse after anal penetration.5,16 References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Thrush can be caught from sexual partners Treating the genitals of asymptomatic male partners of women with thrush is not usually necessary, because it appears to have no effect on the rate of recurrence of infection.2,7 If a male partner develops symptoms of penile thrush, he can be treated with a topical antifungal. Any activity that causes minor abrasions to the vaginal mucosa can lead to an episode and the mouth might be a source of reinfection. Two studies have indicated that oral sex is associated with recurrence of symptoms.16 13. Oral contraceptives can cause thrush The evidence that oral contraceptives can increase the risk of developing thrush is contradictory.11 18. Thrush always produces discharge Thrush does not always produce vaginal discharge. Any discharge present can vary in consistency from a thin, watery fluid to cottage cheese-like white curds.2 Discharge produced by thrush does not smell offensive — if an offensive discharge is present, bacterial vaginosis should be suspected.2 20. 14. 15. 16. 17. 19. 21. Sobel JD. Genital candidosis. Medicine 2001;29:67–71. DenningDW.Fortnightlyreview:managementofgenitalcandidiasis(working group of the British Society for Medical Mycology). BMJ 1995;310:1241–4. Nwokolo NC, Boag FC. Chronic vaginal candidiasis: management in the postmenopausal patient. Drugs Aging 2000;16:335–9. Donders GGG, Prenen H, Verbeke G, et al. Impaired tolerance for glucose in women with recurrent vaginal candidiasis. Gynecol 2002;187:989–93. Young GL, Jewell D. Topical treatment for vaginal candidiasis (thrush) in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd. PRODIGY (2001) Candida — female genital. Sowerby Centre for Health Informatics at Newcastle. Available from: URL: http://www.prodigy.nhs.uk Clinical Effectiveness Group (Association of Genitourinary Medicine and the Medical Society for the Study of Venereal Diseases). National guideline for the management of vulvovaginal candidiasis. Sex Transm Inf 1999;75:S19–S20. Scharbo-DeHaan M, Anderson DG. The CDC 2002 guidelines for the treatment of sexually transmitted disease: implications for women’s health care. J Midwifery Womens Health 2003;48:96–104. British National Formulary. No 46. London: British Medical Association/ Royal Pharmaceutical Society of Great Britain; 2003. Bingham JS. What to do with the patient with recurrent vulvovaginal candidiasis. Sex Transm Inf 1999;75:225–7. Marrazzo J. Candidiasis (vulvovaginal). In: Godlee F, editor. Clinical evidence. 9th ed. London: BMJ Publishing Group; 2003. p. 1980–94. Watson MC, Grimshaw JM, Bond CM, Mollison J, Ludbrook A. Oral versus intra-vaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush). (Cochrane Review). In: The Cochrane Library, Issue 1, 2004. Chichester, UK: John Wiley & Sons, Ltd. Diflucan One. Summary of product characteristics. Available from: URL: http://www.medicines.org.uk/. Sporanox. Summary of product characteristics. Available from: URL: http://www.medicines.org.uk/. Nizoral. Summary of product characteristics. Available from: URL: http://www.medicines.org.uk/. Mårdh PA, Rodrigues AG, Mehmet G, et al. Facts and myths on recurrent vulvovaginal candidosis — a review of epidemiology, clinical manifestations, diagnosis, pathogenesis and therapy. Int J STDs AIDS 2002;13:522–39. Ferris DG, Nyirjesy P, Sobel J, et al. Over-the-counter antifungal drug misuse associated with patient-diagnosed vulvovaginal candidiasis. Obstet Gynecol 2002;99:419–25. Sihvo S, Ahonen R, Mikander H, et al. Self-medication with vaginal antifungal drugs: physicians’ experiences and women’s utilization patterns. Fam Pract 2000;17:145–9. Canestan Once. Summary of product characteristics. Available from: URL: http://www.medicines.org.uk/. Communicable disease surveillance centre: England and Wales. Antimicrobial resistance in 2000. London: Public Health Laboratory Service. Available from: URL: http://www.hpa.org.uk. Accessed 23/1/04. Sobel JD, Zervos M, Reed BD, et al. Fluconazole susceptibility of vaginal isolates obtained from women with complicated Candida vaginitis: clinical implications. Antimicrob Agents Chemother 2003;47:34–8. The National Institute for Clinical Excellence (NICE) is associated with MeReC Publications published by the NPC through a funding contract. This arrangement provides NICE with the ability to secure value for money in the use of NHS funds invested in its work and enables it to influence topic selection, methodology and dissemination practice. NICE considers the work of this organisation to be of value to the NHS in England and Wales and recommends that it be used to inform decisions on service organisation and delivery. This publication represents the views of the authors and not necessarily those of the Institute. © The National Prescribing Centre, The Infirmary, 70 Pembroke Place, Liverpool, L69 3GF. Telephone: 0151 794 8146 16 Fax: 0151 794 8139 www.npc.co.uk www.npc.nhs.uk MeReC Bulletin Volume 14, Number 4
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