Risk of resistance associated with fluconazole prophylaxis: Systematic review

Abstract

Several studies have shown that fluconazole prophylaxis reduces the risk of fungal colonization and of invasive fungal infection in high-risk patients with minimal toxicity. This systematic review was designed to estimate the risk of emergence of colonization and infection either with azole susceptible-dose dependent or with resistant strains. We searched Medline, EMBASE, the Cochrane Collaboration database and our own files for randomized controlled trials assessing the effect of fluconazole on the incidence of fluconazole-resistant strains. This systematic review of randomized clinical trials shows that fluconazole prophylaxis increases the risk for colonization with fluconazole susceptible-dose dependent or with resistant yeasts, the percentage of non-albicans Candida isolates and the percentage of fluconazole susceptible-dose dependent or resistant fungal isolates. Fluconazole prophylaxis did not significantly affect the risk of invasive disease with fluconazole susceptible-dose dependent or resistant fungi. The sample size was too small to assess the effect of fluconazole prophylaxis on the risk for breakthrough infections with non-albicans Candida. Evidence from randomized trials suggests that fluconazole prophylaxis increases the risk for colonization with fluconazole susceptible-dose dependent or with resistant fungi, but does not significantly affect the risk for invasive infections with fluconazole susceptible-dose dependent or with resistant fungi. The risk for breakthrough infections remains a concern and needs to be addressed in large prospective studies.