Therapy of fungal meningitis

There has been an increase in recent years in the number of reported cases of meningitis and brain abscesses caused by fungi. This increase is due to the availability of better diagnostic techniques for fungal infections and the ever-increasing population of immunocompromised hosts (1,2). The patients most susceptible to invasive fungal infections include those with hematologic malignancies; those receiving hyperalimentation, corticosteroids, or cytotoxic drugs; transplant recipients; injection drug abusers; and those with the acquired immunodeficiency syndrome (AIDS). Although many fungi infect only immunologically impaired patients, some will infect normal hosts as well. The successful treatment of central nervous system (CNS) fungal infections is highly dependent on the underlying immune status of the host, as well as on the prompt initiation of appropriate antifungal therapy. However, the diagnosis of these infections may be difficult, and proper therapy often delayed. Furthermore, information on treatment regimens ranges from extensive, as in the case of cryptococcal meningitis, to scanty or nonexistent in the case of rare, opportunistic fungi. For > 3 decades, the standard antifungal agent for the treatment of CNS fungal infections has been amphotericin B. However, the effectiveness of amphotericin B is often eliminated by poor CNS penetration, fungal resistance, and toxicity (3). Because of the problems associated with use of amphotericin B, newer azole antifungal agents have been developed, some of which are efficacious in the therapy of fungal meningitis. We give an overview of the antifungal agents currently available for clinical use and their utility in the treatment of fungal meningitis.