Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2010
Combination flucytosine and high-dose fluconazole compared with fluconazole monotherapy for the treatment of cryptococcal meningitis: a randomized trial in Malawi.
Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 11 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 11 syntheses or guidelines pooled it, 196 citations in OpenAlex.
- Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.The Lancet. Infectious diseases · 2024Guideline
- Prevalence of cryptococcal meningitis among people living with human immuno-deficiency virus and predictors of mortality in adults on induction therapy in Africa: A systematic review and meta-analysis.Frontiers in medicine · 2022Pooled it
- Equity in clinical trials for HIV-associated cryptococcal meningitis: A systematic review of global representation and inclusion of patients and researchers.PLoS neglected tropical diseases · 2021Pooled it
- Efficacy of induction regimens for cryptococcal meningitis in HIV-infected adults: a systematic review and network meta-analysis.Scientific reports · 2021Pooled it
- Cryptococcosis in pregnancy and the postpartum period: Case series and systematic review with recommendations for management.Medical mycology · 2020Pooled it
- Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.Journal of the International AIDS Society · 2020Pooled it
- Treatment for HIV-associated cryptococcal meningitis.The Cochrane database of systematic reviews · 2018Pooled it
- Pooled it
- Comparison of flucytosine and fluconazole combined with amphotericin B for the treatment of HIV-associated cryptococcal meningitis: a systematic review and meta-analysis.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2014Pooled it
- Treatment of invasive fungal infections in cancer patients-updated recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).Annals of hematology · 2014Guideline
- Guideline
- Trial
- How Applicable Is the Single-Dose AMBITION Regimen for Human Immunodeficiency Virus-Associated Cryptococcal Meningitis to High-Income Settings?Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- Trial
- One-year Mortality Outcomes From the Advancing Cryptococcal Meningitis Treatment for Africa Trial of Cryptococcal Meningitis Treatment in Malawi.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Trial
- Trial
- Trial
- A phase II randomized controlled trial adding oral flucytosine to high-dose fluconazole, with short-course amphotericin B, for cryptococcal meningitis.AIDS (London, England) · 2012Trial
- Article
- Clinical Impact and Cost-Effectiveness of Improving Access to Cryptococcal Meningitis Diagnostics and Treatment in Malawi.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
46 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundCryptococcal 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.
methodsFrom 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.
resultsForty-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.
conclusionsThe 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. Clinical trials registration. isrctn.org Identifier: ISRCTN02725351.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.