Combination antifungal therapy for cryptococcal meningitis.

Abstract

To the Editor: In the trial of combination therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection, Day et al. (April 4 issue)1 found a survival benefit associated with 2 weeks of therapy with amphotericin B and flucytosine as compared with amphotericin B monotherapy. The results of this trial reinforce the treatment combination as the standard per current guidelines.2,3 In locations where amphotericin B therapy is not feasible, flucytosine is recommended in combination with fluconazole.2-4 However, the availability of flucytosine worldwide remains grossly inadequate. Flucytosine is currently unregistered and unavailable in most of Asia and Africa, where the disease burden is greatest.5 Even though flucytosine is a simple, orally administered, off-patent drug, only two manufacturers have been approved by the Food and Drug Administration: the originator company, Meda Pharmaceuticals, and the generic manufacturer, Sigmapharm Laboratories. The lack of data about disease burden, concerns regarding toxicity, and high drug costs due to a lack of competition have contributed to a market failure for flucytosine.5 Given the findings of Day et al., sustained efforts from governmental and international stakeholders are now required in order to urgently disseminate and implement World Health Organization (WHO) treatment guidelines, facilitate the registration of flucytosine, motivate generic-drug production, stimulate development of sustained-release formulations of f lucytosine, and widen access to this drug.3,5