ArticlemBio2019
Fluconazole Monotherapy Is a Suboptimal Option for Initial Treatment of Cryptococcal Meningitis Because of Emergence of Resistance.
Article in mBio, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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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
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 70 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
- Antifungal Susceptibility Does Not Correlate With Fungal Clearance or Survival in AIDS-Associated Cryptococcal Meningitis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Trial
- Beyond antifungal susceptibility: molecular mechanisms, detection, and clinical implications of fungal heteroresistance.Molecular biology reports · 2026Review
- Investigating the therapeutic potential of the antibacterial drug nitroxoline in combating cryptococcal infection.PLoS neglected tropical diseases · 2026Article
- Variable ectopic heterochromatin islands provide an alternative route to antifungal heteroresistance inbioRxiv : the preprint server for biology · 2026Article
- Discovery and mechanism of a highly selective, antifungal acetyl-CoA synthetase inhibitor.Nature communications · 2025Article
- Disruption of the ATP-dependent unfoldase ClpX reverses antifungal resistance in Cryptococcus neoformans.Nature communications · 2025Article
- A freely accessible, adaptable hollow-fiber setup to reproduce first-order absorption: illustration with linezolid cerebrospinal fluid pharmacokinetic data.Microbiology spectrum · 2025Article
- Reconstruction and exploitation of a dedicated Genome-Scale Metabolic Model of the human pathogenbioRxiv : the preprint server for biology · 2025Article
- Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance.Journal of fungi (Basel, Switzerland) · 2025Review
- Unveiling new features of the human pathogenComputational and structural biotechnology journal · 2025Article
- Fluconazole Resistance and Heteroresistance in Cryptococcus spp.: Mechanisms and Implications.Revista da Sociedade Brasileira de Medicina Tropical · 2025Review
- Evolution of Laboratory Diagnostics for Cryptococcosis and Missing Links to Optimize Diagnosis and Outcomes in Resource-Constrained Settings.Open forum infectious diseases · 2024Review
- Management and outcome of intracranial fungal infections in children and adults in Africa: a scoping review.BMC infectious diseases · 2024Article
- A ketogenic diet enhances fluconazole efficacy in murine models of systemic fungal infection.mBio · 2024Article
- Antifungal Resistance in Cryptococcal Infections.Pathogens (Basel, Switzerland) · 2024Review
- Novel mitochondrial-targeted alkyl chains act as fungal specific inhibitors ofFrontiers in microbiology · 2024Article
- Novel combinatorial approach: Harnessing HIV protease inhibitors to enhance amphotericin B's antifungal efficacy in cryptococcosis.PloS one · 2024Article
- The organization of the phycobilisome-photosystem I supercomplex depends on the ratio between two different phycobilisome linker proteins.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Cryptococcal meningitis is a lethal disease with few therapeutic options. Induction therapy with fluconazole has been consistently demonstrated to be associated with suboptimal microbiological and clinical outcomes. Exposure to fluconazole causes dynamic changes in antifungal susceptibility, which are associated with the development of aneuploidy. The implications of this phenomenon for pharmacodynamics of fluconazole for cryptococcal meningitis are poorly understood. The pharmacodynamics of fluconazole were studied using a hollow-fiber infection model (HFIM) and a well-characterized murine model of cryptococcal meningoencephalitis. The relationship between drug exposure and both antifungal killing and the emergence of resistance was quantified. The same relationships were further evaluated in a recently described group of patients with cryptococcal meningitis undergoing induction therapy with fluconazole at 800 to 1,200 mg/day. The pattern of emergence of fluconazole resistance followed an "inverted U." Resistance amplification was maximal and suppressed at ratios of the area under the concentration-time curve for the free, unbound fraction of the drug to the MIC (
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Registered trials
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.