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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Combination flucytosine and high-dose fluconazole compared with fluconazole monotherapy for the treatment of cryptococcal meningitis: A randomized trial in malawi
Clinical Infectious Diseases, Volume 50, No. 3, Year 2010
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Description
Background. Cryptococcal meningitis is a major cause of human immunodeficiency virus (HIV)-associated morbidity and mortality in Africa. Improved oral treatment regimens are needed because amphotericin B is neither available nor feasible in many centers. Fluconazole at a dosage of 1200 mg per day is more fungicidal than at a dosage of 800 mg per day, but mortality rates remain unacceptably high. Therefore, we examined the effect of adding oral flucytosine to fluconazole. Methods. From 13 February through 2 December 2008, HIV-seropositive, antiretroviral-naive patients experiencing their first episode of cryptococcal meningitis were randomized to receive (1) 14 days of fluconazole (1200 mg per day) alone or (2) in combination with flucytosine (100 mg/kg per day) followed by fluconazole (800 mg per day), with both groups undergoing 10 weeks of follow-up. The primary end point was early fungicidal activity, derived from quantitative cerebrospinal fluid cultures on days 1, 3, 7, and 14. Secondary end points were safety and 2- and 10-week mortality. Results. Forty-one patients were analyzed. Baseline mental status, cryptococcal burden, opening pressure, CD4+ cell count, and HIV load were similar between groups. Combination therapy was more fungicidal than fluconazole alone (mean early fungicidal activity ± standard deviation, -0.28 ± 0.17 log colony-forming units [CFU]/mL per day vs -0.11 ± 0.09 log CFU/mL per day, P<.001). The combination arm had fewer deaths by 2 weeks (10% vs 37%) and 10 weeks (43% vs 58%). More patients had grade III or IV neutropenia with combination therapy (5 vs 1, within the first 2 weeks; P =.20), but there was no increase in infection-related adverse events. Conclusions. The results suggest that optimal oral treatment for cryptococcal meningitis is high-dose fluconazole with flucytosine. Efforts are needed to increase availability of flucytosine in Africa. © 2010 by the Infectious Diseases Society of America. All rights reserved.
Authors & Co-Authors
Nussbaum, Jesse C.
Unknown Affiliation
Jackson, Arthur Timothy
Unknown Affiliation
Namarika, Dan C.
Unknown Affiliation
Phulusa, Jacob N.
Unknown Affiliation
Kenala, Jullita
Unknown Affiliation
Kanyemba, Creto
Unknown Affiliation
Jarvis, Joseph N.
Unknown Affiliation
Jaffar, Shabbar S.
Unknown Affiliation
Hosseinipour, Mina C.
Unknown Affiliation
Kamwendo, Deborah D.
Unknown Affiliation
van der Horst, Charles Michael
Unknown Affiliation
Harrison, Thomas Stephen
Unknown Affiliation
Statistics
Citations: 178
Authors: 12
Affiliations: 9
Identifiers
Doi:
10.1086/649861
ISSN:
10584838
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Cohort Study
Study Approach
Quantitative
Study Locations
Malawi