Risk of resistance associated with fluconazole prophylaxis: systematic review

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.