Flucytosine and its clinical usage

Abstract

Flucytosine is an antifungal agent first licensed in the 1970's. However, its clinical value has long been overlooked and its availability across the globe is limited. This review highlights the important clinical and pharmacological aspects of flucytosine. This a narrative review of the clinical and in vitro susceptibility literature, with a focus on clinical uses for flucytosine. Detailed literature review including early literature related to primary and acquired resistance to flucytosine. Flucytosine has good antifungal activity against Cryptococcus species, Candida species, and dematiaceous fungi. Its water solubility enables good penetration into the eye, urinary tract, central nervous system (CNS), cardiac vegetations and fungal biofilms. In combination with amphotericin B, it shows early fungicidal activity against Cryptococcus species, and this translates to ~20% improved survival in cryptococcal meningitis. Combination therapy also reduces the mortality of Candida meningitis, and should be used in neonatal candidiasis because of the high frequency of CNS infection. Monotherapy for urinary candidiasis is under-studied, but is usually effective. It is probably valuable in the treatment of Candida endocarditis and endophthalmitis: there are few data. It is not effective for aspergillosis or mucormycosis. Flucytosine monotherapy of urinary candidiasis resulted in 22% developing resistance on therapy and failing therapy, and in 29% of 21 patients with cryptococcosis. Certain regions of the world still do not have access to flucytosine compromising the management of certain severe fungal infections. Flucytosine has an important role in combination therapy for yeast and dematiaceous infections and probably as monotherapy for urinary candidiasis, with a modest risk of resistance emergence. Facilitating access to flucytosine in those regions (especially low-income countries) might alleviate the mortality of invasive fungal diseases.

Keywords: Candida endophthalmitis; Candida meningitis; Candida species; Candida urinary tract infection; Cryptococcus species; antifungal resistance; combination therapy; dematiaceous fungi; flucytosine; fungal endocarditis.