Oral versus intra‐vaginal imidazole and triazole anti‐fungal treatment of uncomplicated vulvovaginal candidiasis (thrush)

Munira Nurbhai, Jeremy Grimshaw, Margaret Watson, Christine M Bond, Jill A Mollison, Anne Ludbrook

Anti-fungals are available for oral and intra-vaginal treatment of uncomplicated vulvovaginal candidiasis (thrush). The primary objective of this review was to assess the relative effectiveness of oral versus intra-vaginal anti-fungals for the treatment of uncomplicated vulvovaginal candidiasis. The secondary objectives of the review were to assess the cost-effectiveness, safety and patient preference of oral versus intra-vaginal anti-fungals. The following sources were searched for the original review: The Cochrane Library (Issue 4, 1999), MEDLINE (January 1985 to May 2000), EMBASE (January 1980 to January 2000) and the Cochrane Sexually Transmitted Disease (STD) Group Specialised Register of Controlled Trials. The manufacturers of anti-fungals available in the UK were contacted. For the update, CENTRAL (January 2000 to August 2006), PUBMED (January 2000 to August 2006), EMBASE (January 2000 to August 2006) and the Cochrane STD Group Specialised Register were searched in August 2006. The reference lists of retrieved articles were reviewed manually. Randomised controlled trials published in any language. Trials had to compare at least one oral anti-fungal with one intra-vaginal anti-fungal. Women (aged 16 years or over) with uncomplicated vulvovaginal candidiasis. The diagnosis of vulvovaginal candidiasis to be made mycologically (i.e. a positive culture and / or microscopy for yeast). Trials were excluded if they solely involved subjects who were HIV positive, immunocompromised, pregnant, breast feeding or diabetic. The primary outcome measure was clinical cure. Two reviewers screened titles and abstracts of the electronic search results and full text of potentially relevant papers. Independent duplicate abstraction was performed by two reviewers. Disagreements regarding trial inclusion or data abstraction were resolved by discussion between the reviewers. Odds ratios were pooled using the fixed effects models (except for two analyses when random effects models were used because of potentially important heterogeneity). Two new trials reporting three comparisons were found in the update. Nineteen trials are included in the review, reporting 22 oral versus intra-vaginal anti-fungal comparisons. No statistically significant differences were shown between oral and intra-vaginal anti-fungal treatment for clinical cure at short term (OR 0.94, 95% CI, 0.75 to 1.17) and long term (OR 1.07, 95% CI, 0.82 to 1.41) follow-up. No statistically significant differences for mycological cure were observed between oral and intra-vaginal treatment at short term (OR 1.15, 95% CI, 0.94 to 1.42). There was a statistically significant difference for long term follow-up (OR 1.29, 95% CI, 1.05 to 1.60) in favour of oral treatment, however the clinical significance of this result is uncertain. Two trials each reported one withdrawal from treatment due to an adverse reaction. Treatment preference data were poorly reported. No statistically significant differences were observed in clinical cure rates of anti-fungals administered by the oral and intra-vaginal routes for the treatment of uncomplicated vaginal candidiasis. No definitive conclusion can be made regarding the relative safety of oral and intra-vaginal anti-fungals for uncomplicated vaginal candidiasis. The decision to prescribe or recommend the purchase of an anti-fungal for oral or intra-vaginal administration should take into consideration: safety, cost and treatment preference. Unless there is a previous history of adverse reaction to one route of administration or contraindications, women who are purchasing their own treatment should be given full information about the characteristics and costs of treatment to make their own decision. If health services are paying the treatment cost, decision-makers should consider whether the higher cost of some oral anti-fungals is worth the gain in convenience, if this is the patient's preference.