Treatment of Cryptococcus neoformans meningoencephalitis in HIV-infected patients
- Gary M Cox, MD
Gary M Cox, MD
- Professor of Medicine
- Duke University Medical Center
- John R Perfect, MD
John R Perfect, MD
- Professor of Medicine
- Duke University Medical Center
Cryptococcus neoformans meningoencephalitis is one of the leading opportunistic infections seen in patients with untreated AIDS . Management of these severely immunocompromised patients includes antifungal therapy combined with antiretroviral therapy (ART), with careful monitoring for complications related to the invasive fungal infection and the inflammatory syndromes secondary to immune recovery .
This topic is devoted to the treatment of the HIV-infected host with C. neoformans meningitis. The epidemiology, clinical manifestations, diagnosis, treatment and management of complications of disease are discussed elsewhere. C. neoformans infection outside the central nervous system, C. neoformans infection in HIV seronegative patients, and Cryptococcus gattii infection are also discussed separately. (See "Epidemiology, clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-infected patients" and "Microbiology and epidemiology of Cryptococcus neoformans infection" and "Immune reconstitution inflammatory syndrome" and "Clinical management and monitoring during antifungal therapy of the HIV-infected patient with cryptococcal meningoencephalitis" and "Cryptococcus neoformans infection outside the central nervous system" and "Clinical manifestations and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-seronegative patients" and "Treatment of Cryptococcus neoformans meningoencephalitis and disseminated infection in HIV seronegative patients" and "Cryptococcus gattii infection: Microbiology, epidemiology, and pathogenesis" and "Cryptococcus gattii infection: Clinical features and diagnosis" and "Cryptococcus gattii infection: Treatment".)
The primary antifungal agents used for the treatment of cryptococcal meningoencephalitis include intravenous amphotericin B deoxycholate or its lipid formulations, oral flucytosine, and oral fluconazole. For most patients, liposomal preparations of amphotericin B are preferred to minimize the risk of toxicity and improve the ability to give an uninterrupted induction period of treatment. Echinocandin antifungals do not have significant activity against C. neoformans and should not be used to treat this infection . (See "Pharmacology of azoles" and "Pharmacology of amphotericin B".)
Combination therapy with amphotericin B and flucytosine is fungicidal (inhibition leads to cell death), while fluconazole alone is only fungistatic (ie, inhibits without killing). Importantly, the use of a fungicidal regimen during the initial phase of therapy has been associated with better clinical outcomes . (See 'Induction and consolidation therapy' below.)
The HIV-infected patient with advanced immunosuppression (CD4 cell count <50 cells/microL) is at risk for severe cryptococcal meningoencephalitis, which is uniformly fatal within approximately two weeks if untreated . Common presenting symptoms include fever, headache, photophobia, nausea, and vomiting; patients with fulminant disease may present with coma. Predictors of poor outcome include high cerebrospinal fluid (CSF) cryptococcal antigen levels (titer >1:1024), low body weight, poor CSF inflammatory response (<20 cells/ul of CSF), and altered mental status on presentation . (See "Epidemiology, clinical manifestations, and diagnosis of Cryptococcus neoformans meningoencephalitis in HIV-infected patients", section on 'Clinical manifestations'.)
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- ANTIFUNGAL AGENTS
- GENERAL PRINCIPLES
- CLINICAL TRIAL DATA
- Induction and consolidation therapy
- Maintenance therapy
- APPROACH TO ANTIFUNGAL TREATMENT
- Induction and consolidation
- SPECIAL TREATMENT CONSIDERATIONS
- Patients without risk of nephrotoxicity
- Patients at risk of renal insufficiency
- Patients with established renal insufficiency
- ADVERSE EVENTS
- PATIENTS WHO ARE INTOLERANT OF AMPHOTERICIN B AND/OR FLUCYTOSINE
- WHEN TO INITIATE ANTIRETROVIRAL THERAPY
- DRUG INTERACTIONS
- THERAPEUTIC COMPLICATIONS
- DISCONTINUATION OF MAINTENANCE THERAPY
- PREVENTING SYMPTOMATIC DISEASE
- Primary prevention
- Screening and treatment of early infection
- SUMMARY AND RECOMMENDATIONS