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Treating thrush

Uncomplicated thrush
Results
Recurrent thrush
Results
Adverse event
Comment

Most women of reproductive years experience at least one episode of vulvovaginal candidiasis (thrush), caused by infection with one or more species of Candida, most often albica. Anti-fungal drugs can be administered orally or vaginally. About 1 in 10 women who experience an episode of thrush can go on to develop recurrent candidiasis, though this has no recognised risk factors. Management of recurrent candidiasis is difficult, and Bandolier readers have asked for evidence. A Cochrane review [1] has looked at oral versus intra-vaginal anti-fungal treatments of uncomplicated thrush, and a recent randomised trial [2] examined treating recurrent infection.

Uncomplicated thrush

The Cochrane review [1] examined uncomplicated thrush, acute episodes occurring less frequently than four times a year in women aged 16 years or older. Diagnosis was by culture or microscopy, and studies with immunocompromised, pregnant, breast feeding or diabetic women were not included.

Trials had to be randomised, and compare any imidazole or triazole anti-fungal used vaginally with an oral equivalent (fluconazole or itraconazole). Treatments generally lasted less than a week. Various outcomes were examined, including clinical cure in the short term (usually about one or two weeks) or long term (generally about four weeks).

Results

There was no difference in long term clinical or mycological cure for oral fluconazole compared with vaginal clotrimazole. Seven trials with 836 women had long term cure rates of 83% for oral and 82% for intravaginal treatment (Figure 1), as well as high rates of women with mycological cure on culture or microscopy.



Figure 1: Long-term cure with oral or intra-vaginal imidazole or triazole antifungal





Recurrent thrush

In a large randomised trial [2], women aged 18 years or older were required to have active candida vaginitis, with at least four documented episodes in the previous 12 months, and positive culture or microscopy of vaginal secretions. Clinical scoring was based on presence of symptoms of pruritus, burning, or irritation, and signs of erythema, oedema, and excoriation or fissures (each scored 0-3, maximum score 18). Women excluded were those with negative culture, who were pregnant, had mixed infections, had previous recent anti-fungal treatment, or who were immunocompromised.

There was an induction phase to ensure that women fulfilled entry criteria, followed by receipt of three 150 mg oral doses of fluconazole over nine days. At 14 days women had a vaginal examination and were entered into the trial if they had a negative culture and a clinical cure (symptom score of 3 or less out of 18).

Treatment was with a single 150 mg oral dose of fluconazole or placebo tablet every week for six months. Clinic visits occurred every month for six months, then at nine and 12 months. Clinical scoring and detailed pelvic examinations for fungal culture were made at these visits.

Results

The main analysis was on 343 women initially clear of thrush, with an average age of 34 (range 18 to 65) years. While all were cured at the start of the study, recurrence was rapid with placebo treatment (Figure 2), so that almost half had a recurrence by three months, two-thirds by six months, and four out of 10 by 12 months.



Figure 2: Recurrence of thrush with weekly fluconazole or placebo for six months (arrow)





Weekly treatment with oral fluconazole meant that over the six-month treatment period, only 1 in 10 women had a recurrence of thrush (Figure 2). When treatment stopped, however, there was a rapid increase in recurrence, so that about half of the women had a recurrence after a further six months without fluconazole treatment.

At the end of six months of treatment of women with recurrent thrush initially free from symptoms and with negative vaginal culture, 9% of women had recurrence with fluconazole compared with 64% with placebo. The number needed to treat for six months with weekly oral fluconazole 150 mg for one woman continuing to be free of thrush was 1.8 (1.6 to 2.2). There was no indication of the emergence of resistant strains of Candida.

Adverse event

Adverse events with these treatments appear to be few. The review of oral and vaginal anti-fungal treatments [1], and the randomised trial [2] reported two withdrawals because of adverse events from treatment with oral fluconazole, or other oral anti-fungals.

Comment

Oral antifungal agents are highly effective for treating a single episode of thrush, and oral fluconazole is available without prescription in some countries. Weekly oral fluconazole is effective for recurrent thrush, though not after treatment stops, even for six months.

Weekly treatment is expensive for health services or individuals, costing about £350 a year. Whether weekly treatment is better than twice weekly or monthly oral fluconazole is not known. We don't know the optimal strategy, but long-term cure remains elusive.

References:

  1. MC Watson et al. Oral versus intravaginal imidazole and triazole anti-fungal treatment of uncomplicated vulvovaginal candidiasis (thrush). The Cochrane Database of Systematic Reviews 2001 issue 3.
  2. JD Sobel et al. Maintenance fluconazole therapy for recurrent vulvovaginal candidiasis. New England Journal of Medicine 2004 351: 876-883.

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