Thrush: detection and management in community pharmacy

Vulvovaginal candidiasis, or thrush, is the most common cause of vaginitis (inflammation of the vagina) and vulvovaginitis (inflammation of the vulva and vagina region). Candidiasis is typically caused by an overgrowth of the fungal yeast Candida albicans. The National Institute for Health and Care Excellence (NICE) states that C. albicans accounts for 80–92% of cases; C. glabrata is responsible for a further 5% of cases; and C. tropicalis, C. parapsilosis, C. krusei, C. kefyr, C. guilliermondii and Saccharomyces cerevisiae account for most of the remaining cases^[1].

Candidiasis is very common, with 70–75% of women reportedly experiencing the condition at least once and 40–50% of women reportedly experiencing it two or more times throughout their lives^[2],[3]. These figures, although widely claimed in scientific literature, are estimates based on expert opinion from the 1970s^[4], with accurate incidence and prevalence rates currently lacking in the UK. However, it is estimated that Candida species could be isolated from 20% of vaginal swabs from otherwise healthy, asymptomatic women of reproductive age at any one time^[5].

Although thrush can affect other areas of the skin, such as armpits, groin and mouth (oral thrush), this article will focus mainly on the diagnosis and treatment of genital thrush.

Risk factors

The vaginal microbiome is diverse, however, most women have lactic acid-producing Lactobacillus species, which accounts for the acidic pH range of the vagina^[6]. The composition of microflora is also dynamic, with increased change during menstruation and sexual activity^[7]. As the majority of women are thought to be colonised with Candida species without obvious symptoms at some point in their lives, it has been proposed that the dynamic nature of the vaginal microbiome is a critical factor that leads to colonisation by Candida, as well as contributing to commensal
Candida species becoming pathogenic^[5]. The following risk factors have been identified as leading to colonisation and/or symptomatic candidiasis:

• Genetics (e.g. black British, familial history);
• Changes in circulating hormones (e.g. pregnancy, combined oral contraceptive pill/hormone replacement therapy, menstruation);
• Immunosuppression (e.g. HIV, corticosteroids);
• Diabetes (i.e. poorly controlled [see Box 1]);
• Vulvar dermatosis;
• Antibiotics;
• Sexual activity (e.g. intercourse, orogenital contact);
• Changes in vaginal pH^[1],[5].

Symptoms and differential diagnosis

The most common causes of vaginitis in symptomatic women are bacterial vaginosis (BV), vaginal candidiasis (most commonly a C. albicans strain) and trichomoniasis (a protozoal infection). Thrush symptoms and signs are very common, but the sensitivity and specificity of any single sign or symptom are suboptimal for diagnosis. The following self-reported symptoms are typical^[5],[8]:

• Pruritus (sensitivity 50–91%; specificity 47–64%);
• Cheesy discharge (sensitivity 65%; specificity 73%);
• Irritation (i.e. redness or swelling) (sensitivity 20–28%; specificity 86–92%);
• Another yeast infection (sensitivity 35%; specificity 95%).

Physician-reported ‘curdy’ discharge has a relatively high predictive value of 72% sensitivity and 100% specificity.

pH testing could be used to help assess the cause of symptoms; candidiasis (pH≤4.5), BV (pH>4.5) or Trichomonas vaginalis (pH>4.5)^[1].

Thrush is typically non-odorous; self-reported malodour that is ‘fishy’ has a sensitivity of 46% and specificity of 45% for BV. Physician-reported odour of ‘high cheese’ reaches a sensitivity of 78% and specificity of 75% for BV. Other symptoms and signs of BV include physician-reported yellow discharge with sensitivity of 30–89% and specificity of 85–93%^[8].

Classification of thrush

To help support treatment choice, vulvovaginal candidiasis has been classified in NICE guidance as uncomplicated or complicated^[1].

Uncomplicated vulvovaginal candidiasis is defined as:

• Sporadic or infrequent;
• Mild to moderate;
• Likely to be owing to C. albicans;
• Is not associated with risk factors (e.g. pregnancy or poorly controlled diabetes).

Whereas, complicated vulvovaginal candidiasis includes:

• Recurrent infection — defined as four or more documented episodes in one year, with at least partial resolution of symptoms between episodes;
• Severe infection;
• Infection with yeasts other than C. albicans;
• Infection during pregnancy;
• Infection in women with uncontrolled diabetes, women with immunocompromising conditions (e.g. HIV infection) and women taking immunosuppressive drugs (e.g. systemic corticosteroids).

Microscopy is generally not required for uncomplicated thrush; however, complicated cases, such as recurrent infection, may require laboratory testing to confirm the diagnosis^[1].

Treatment

Azole therapies are fungistatic agents and are considered to be the crux of therapy^[9],[10]. They act by inhibiting Candida yeast cells from transforming into hyphae^[9]. Various azoles are available, including clotrimazole, econazole, fenticonazole, fluconazole, itraconazole and miconazole^[9],[10]. Many of these pharmacological agents are available in different formulations and do not require a prescription (see Table 1)^[11],[12].

Short courses (1–3 days) of topical azoles are usually effective for the treatment of uncomplicated thrush and are more beneficial than nystatin^[3]. Nystatin, a polyene macrolide antibiotic, may also be used in the treatment of Candida infections, including thrush^[9],[10]. For uncomplicated thrush, topical and oral azoles are equally effective^{[10],[13],[14]}; hence, choice of formulation should be based on the patient’s preference and the availability of the product^[10].

Patient characteristics

The age of the patient should be considered^[1]. The use of topical agents may be less acceptable and more difficult to administer for women aged over 60 years. On the other hand, topical agents are the treatment of choice for girls aged 12–15 years, as oral and intravaginal formulations are not recommended. Pharmacists may prefer to refer girls in this age group to a medical practitioner.

A further factor that may influence treatment choice is co-administration with a patient’s regular medicines. Azoles and nystatin can interact with other medicines. Even topical azoles can lead to severe interactions with prescribed oral therapy. For example, topical miconazole, a potent cytochrome P450 enzyme inhibitor, interacts with warfarin therapy and can lead to large changes in international normalised ratio (INR). Hence, co-administration is not recommended, except in cases where close monitoring of INR is possible^[15],[16].

When discussing treatment options with patients, pharmacists and healthcare professionals need to inform them that topical thrush treatment can damage latex condoms and diaphragms; therefore, alternative contraception or treatment formulations may be more appropriate^[10]. However, oral formulations are not recommended for pregnant women (see Box 2), for whom only topical azoles should be used^[3],[17].

Side effects

Therapy with azoles is generally well tolerated; however, topical azoles may cause local side effects (e.g. irritation at the site of application), while oral azoles may cause gastrointestinal symptoms (e.g. nausea) and headaches
^[3],[9].

Recurrent or persistent thrush

Typically, recurrent thrush refers to four or more mycologically proven episodes in a 12-month period; however, there is a lack of consensus on the exact number of episodes required for a diagnosis of recurrent thrush, with some definitions requiring only three episodes per year^[3],[18]. Women who experience recurrent or persistent thrush that is still present after treatment require evaluation and testing to rule out differential diagnoses^[3]. For women with recurrent thrush, a longer duration of therapy may be recommended at the initial presentation. For example, the initial treatment may include up to 14 days of topical therapy or three doses of oral therapy over 1 week^[3]. After initial therapy, the first-line maintenance regimen involves weekly 150mg oral fluconazole for a 6-month period^[2],[3]. The risk of resistance is increased for ongoing or prophylactic therapy, which should be administered only under supervision by a physician.

Drug-resistant thrush and treatment failure

Although reports of azole -resistant candidiasis are of concern^[5], the nature of fungal organisms is such that occurrence of drug resistance is lower than that of bacterial and viral infections. C. albicans resistance is very low and treatment failure is typically a result of poor adherence to treatment; incorrect use of treatment or misdiagnosis/differential diagnosis; or that another strain of Candida (e.g. C. glabrata) may be the cause^[1],[5]. Referral for additional investigation (e.g. vaginal specimen for microscopy, culture and sensitivity, pH testing) is advised. Boric acid 600mg capsules (unlicensed), inserted intravaginally (not taken orally), once or twice daily for 14 days have shown some success in the treatment of resistant vaginal candidiasis^[10],[19].

For complicated cases, multiple doses of treatment may be required^[1]. For all women, pharmacists should advise seeking further medical attention if the symptoms do not resolve within 7–14 days.

Thrush in men

Although thrush is often thought of as a female condition, it can also affect men and may be present without causing any symptoms^[20]. Asymptomatic men, including those who may have engaged in sexual activity with a woman who has thrush, do not require treatment^{[3],[9],[21],[22]}. Symptomatic men who present with thrush usually experience redness, discharge and irritation at the head of the penis and under the foreskin^[20],[23]. As with women, the discharge looks like cottage cheese; however, an unpleasant smell may also be present^[20],[23]. Treatment is the same as that for women; topical creams and oral capsules containing an azole are usually recommended for uncomplicated, acute thrush^[20].

Lifestyle and self-management

Various lifestyle factors may contribute to the development of thrush and the discomfort associated with its symptoms. Men and women with thrush should be advised to avoid using irritants (e.g. soaps and fragranced shower gels) in the genital area when showering^[20]. Pharmacists and healthcare professionals should recommend fragrance-free and soap-free alternatives, and that showers are preferable to baths^[20],[23]. Both men and women should also be advised to keep their genitals clean and dry as Candida species, like many fungi, grow in damp, moist environments^[20],[23]. Loose-fitting cotton underwear is also recommended^[23].

Although most people do not acquire uncomplicated thrush through sex^[3], patients should avoid sex or use condoms (if engaging in sexual intercourse) when thrush symptoms are present^[23].

Dietary changes or adjuvant use of probiotics have been noted to increase the rate of clinical cure and absence of abnormal laboratory results, as well as short-term relapse within one month^[24]. However, the effectiveness of probiotics is strain dependent.

Box 3 describes a common scenario of a female presenting in a community pharmacy requesting advice about thrush.