title: Flucytosine and cryptococcosis: time to urgently address the worldwide accessibility of a 50-year-old antifungal.
abstract: Current, widely accepted guidelines for the management of HIV-associated cryptococcal meningoencephalitis (CM) recommend amphotericin B combined with flucytosine (5-FC) for ≥2 weeks as the initial induction treatment of choice. However, access to flucytosine in Africa and Asia, where disease burden is greatest, is inadequate at present. While research into identifying effective and well-tolerated antifungal combinations that do not contain flucytosine continues, an ever-increasing body of evidence from in vitro, in vivo and clinical studies points to the benefits of flucytosine in the treatment of CM in both intravenous combinations with amphotericin B and oral combinations with high-dose fluconazole. This article provides an up-to-date review of this evidence, and the current issues and challenges regarding increasing access to this key component of combination antifungal therapy for cryptococcosis.
authors.affiliation: Cryptococcal Meningitis Group, Research Centre for Infection and Immunity, Division of Clinical Sciences, St. George's Hospital Medical School, London, UK.
authors.forename: Angela
authors.initials: A
authors.lastname: Loyse
authors.forename: Françoise
authors.initials: F
authors.lastname: Dromer
authors.forename: Jeremy
authors.initials: J
authors.lastname: Day
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Harrison
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000453:epidemiology; D000349:Africa / Q000453:epidemiology; D000666:Amphotericin B / Q000627:therapeutic use; D000935:Antifungal Agents / Q000600:supply & distribution* / Q000627:therapeutic use*; D001208:Asia / Q000453:epidemiology; D015725:Fluconazole / Q000627:therapeutic use; D005437:Flucytosine / Q000600:supply & distribution* / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000453:epidemiology
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine
keywords: 5-FC; 5-FC safety; access to essential antifungals for cryptococcal meningitis; combination antifungal therapy; cryptococcal meningitis; cryptococcal meningitis treatment guidelines; opportunistic infection