Cryptococcal Meningitis: Diagnosis and Management Update

Abstract

Recent advances in the diagnosis and management of cryptococcal meningitis are promising and have been improving long-term survival. Point of care testing has made diagnosing cryptococcal meningitis rapid, practical, and affordable. Targeted screening and treatment programs for cryptococcal antigenemia are a cost effective method for reducing early mortality on antiretroviral therapy (ART). Optimal initial management with amphotericin and flucytosine improves survival against alternative therapies, although amphotericin is difficult to administer and flucytosine is not available in middle or low income countries, where cryptococcal meningitis is most prevalent. Controlling increased intracranial pressure with serial therapeutic lumbar punctures has a proven survival benefit. Delaying ART initiation for 4 weeks after the diagnosis of cryptococcal meningitis is associated with improved survival. Fortunately, new approaches have been leading the way toward improving care for cryptococcal meningitis patients. New trials utilizing different combinations of antifungal therapy are reviewed, and we summarize the efficacy of different regimens.

Keywords: AIDS; Antifungal therapy; Antiretroviral therapy; CM-IRIS; Cryptococcal meningitis; HIV; Immune reconstitution inflammatory syndrome; Review.

Figure 1

Early fungicidal activity (EFA) of induction regimens for the treatment for cryptococcal meningitis, measured as log₁₀ clearance of yeasts per mL of CSF per day in quantitative CSF culture. Notes: Values are the means with 95% Confidence Intervals as pooled from Table 2 (citation are in parenthesis). Abbreviation: AmB, amphotericin; fluc, fluconazole; CFU, colony-forming units; CSF, cerebrospinal fluid.