Cryptococcal Meningitis: Current Approaches to Management in Patients With and Without AIDS
- 245 Downloads
Cryptococcal meningitis is a life-threatening fungal infection of the central nervous system (CNS). Its management is characterized by the administration of initial combination antifungal therapy by following the principles of induction, consolidation, and maintenance therapy with aggressive management of elevated intracranial pressure (ICP). These tenets apply to patients with and without AIDS. Recent prospective trials on combination antifungal therapy, and the timing of the initiation of highly active antiretroviral therapy (HAART), suggest amphotericin B plus flucytosine and initiation of HAART are optimal therapy for management of patients with AIDS and cryptococcal meningitis. The paucity of prospective data on the management of cryptococcal meningitis in patients without AIDS is the most challenging aspect of formulating treatment guidelines, but the principles of induction, consolidation, and maintenance still apply. Combination antifungal therapy with a lipid formulation of amphotericin B plus flucytosine is generally indicated for this group, especially for those with a predisposition to renal dysfunction. Future research targeting this population may further inform recommendations.
KeywordsCryptococcal meningitis Cryptococcal meningoencephalitis Cryptococcus neoformans Cryptococcus gattii Cryptococcus Cryptococcosis Cryptococcemia Cryptococcoma Immune reconstitution inflammatory syndrome HIV AIDS Opportunistic infection Intracranial pressure
No potential conflict of interest relevant to this article was reported.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 2.•• Park BJ, Wannemuehler KA, Marston BJ, et al.: Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 2009, 23:525–530, This article provides an excellent recent characterization of the true global impact of cryptococcosis.CrossRefPubMedGoogle Scholar
- 3.•• Perfect JR, Dismukes WE, Dromer F, et al.: Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2010, 50:291–322, This article is an outstanding review of the management of cryptococcosis including both cryptococcal meningitis and non-CNS cryptococcal disease.CrossRefPubMedGoogle Scholar
- 6.•• Brouwer AE, Rajanuwong A, Chierakul W, et al.: Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomized trial. Lancet 2004, 363:1764–1767, This article is the first paper to define EFA and its use as well as test and compare combination antifungal therapy based on clearance of cryptococcal CFU from CSF.CrossRefPubMedGoogle Scholar
- 8.•• Bicanic T, Wood R, Meintjes G, et al.: High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial. Clin Infect Dis 2008, 47:123–130, This article describes a prospective trial evaluating two separate amphotericin B doses using the cryptococcal CFU clearance rate from the CSF (EFA) as an endpoint.CrossRefPubMedGoogle Scholar
- 9.• Bicanic T, Muzoora C, Brouwer AE, et al.: Independent association between rate of clearance of infection and clinical outcome of HIV-associated cryptococcal meningitis: analysis of a combined cohort of 262 patients. Clin Infect Dis 2009, 49:702–709, This article reports a combined cohort of patients for whom cryptococcal CFU clearance rate from the CSF (EFA) was known and shown to be associated with 2-week and 10-week mortality.CrossRefPubMedGoogle Scholar
- 10.• Dromer F, Bernede-Bauduin C, Guillemot D, Lortholary O: Major role for amphotericin B-flucytosine combination in severe cryptococcosis. PLoS ONE 2008, 3:1–9, This article reports a prospective observational trial evaluating outcomes of patients who did or did not receive flucytosine as part of combination antifungal therapy for cryptococcosis.CrossRefGoogle Scholar
- 13.• Nussbaum JC, Jackson A, Namarika D, et al.: Combination flucytosine and high-dose fluconazole compared with fluconazole monotherapy for the treatment of cryptococcal meningitis: a randomized trial in Malawi. Clin Infect Dis 2010, 50:338–344, This article describes a prospective trial evaluating the optimal oral regimen for cryptococcal meningitis.CrossRefPubMedGoogle Scholar
- 14.Pappas PG: Fluconazole plus amphotericin B vs amphotericin B alone for primary treatment of AIDS-associated cryptococcal meningitis: results of a phase II trial [abstract M626]. In Program and abstracts of the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology; 2007.Google Scholar
- 19.•• Sungkanuparph S, Filler SG, Chetchotisakd P, et al.: Cryptococcal immune reconstitution syndrome after antiretroviral therapy in AIDS patients with cryptococcal meningitis: a prospective multicenter study. Clin Infect Dis 2009, 49:931–934, This article describes a prospective study evaluating the timing and outcomes of IRIS associated with cryptococcal meningitis in HIV-positive patients who begin HAART.CrossRefPubMedGoogle Scholar
- 27.Chen S, Sorrell T, Nimmo G, et al.: Epidemiology and host- and variety-dependent characteristics of infection due to Cryptococcus neoformans in Australia and New Zealand. Australasian Cryptococcal Study Group. Clin Infect Dis 2000, 31:499–508.Google Scholar