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Antibiotic scripts for LRTI 'high'

anti-fungals

to treat THRUSH?

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 one 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; we have

often been asked for evidence.

A Cochrane review1 has looked at oral versus intravaginal anti-fungal treatments of uncomplicated thrush, and a recent randomised tria · 2 examined treating recurrent infection.

Oral or intra-vaginal

anti-fungal treatments?

The Cochrane review examined uncomplicated thrush, acute episodes occurring less frequently than four times a year in women aged 16 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 compared 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 one or two weeks) or long-term (generally about four weeks).

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 per cent for oral and 82 per cent for intravaginal treatment (figure 1), as well as high rates of women with mycological cure on culture or microscopy.

Can anti-fungals prevent recurrent thrush?

In a large randomised tria · 2, women aged 18 or older were required to have active

C. vaginitis, with at least four documented episodes in 12 months, and positive culture or microscopy of vaginal secretions. Clinical scoring was based on the 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, previous recent anti-fungal treatment, or were immunocompromised.

There was an induction phase to ensure women fulfilled entry criteria, followed by receipt of three 150mg 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).

Treatment was with a single 150mg 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.

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 (figure 2) ­ almost half had a recurrence by three months, two-thirds by six months, and four out of 10 by 12 months.

With weekly oral fluconazole, only one in 10 women had a recurrence of thrush (see box). But when treatment stopped there was a rapid increase in recurrence. About half the women had a recurrence after a further six months without fluconazole .

At the end of six months of treatment of women with recurrent thrush initially free from symptoms and with negative vaginal culture, 9 per cent had recurrence with fluconazole compared with 64 per cent with placebo. The number needed to treat for six months with weekly oral fluconazole 150mg 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.

The bottom line

Oral anti-fungals are highly effective for a single episode of thrush. Weekly oral fluconazole is effective for recurrent thrush, though not after treatment stops, even for six months.

Weekly treatment is expensive, 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.

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