ArticleOpen forum infectious diseases2019
Minimum Inhibitory Concentration Distribution of Fluconazole against Cryptococcus Species and the Fluconazole Exposure Prediction Model.
Article in Open forum infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Once-Daily Dolutegravir-Based Antiretroviral Therapy Among Adults With Advanced HIV Disease Receiving 1 Month of Daily Rifapentine and Isoniazid for Tuberculosis-Preventive Therapy and Fluconazole for Treatment of Cryptococcal Meningitis: Results of a Pharmacokinetic Study.Open forum infectious diseases · 2026Article
- In vitro and in vivo efficacy of the antimycobacterial molecule SQ109 against the human pathogenic fungus, Cryptococcus neoformans.PLoS neglected tropical diseases · 2025Article
- InFuture microbiology · 2025Article
- Therapeutic role of fluconazole in immunocompetent patients with pulmonary cryptococcosis: A case report.IDCases · 2025Article
- Inhibition of RhoA Prevents Cryptococcus neoformans Capsule Glucuronoxylomannan-Stimulated Brain Endothelial Barrier Disruption.The Journal of infectious diseases · 2024Article
- Complex Decisions in HIV-Related Cryptococcosis: Addressing Second Episodes of Cryptococcal Meningitis.Current HIV/AIDS reports · 2024Review
- Antifungal Resistance in Cryptococcal Infections.Pathogens (Basel, Switzerland) · 2024Review
- 5-Flucytosine Longitudinal Antifungal Susceptibility Testing ofOpen forum infectious diseases · 2023Article
- Article
- Lack of Association between Fluconazole Susceptibility andJournal of fungi (Basel, Switzerland) · 2022Article
- Epidemiological and Clinical Characteristics, Antifungal Susceptibility, and MLST-Based Genetic Analysis ofJournal of fungi (Basel, Switzerland) · 2022Article
- Collateral consequences of agricultural fungicides on pathogenic yeasts: A One Health perspective to tackle azole resistance.Mycoses · 2022Review
- Fungicide effects on human fungal pathogens: Cross-resistance to medical drugs and beyond.PLoS pathogens · 2021Review
- Successful Treatment of Cryptococcal Meningitis and Cryptococcoma with Isavuconazole in a Patient Living with HIV.Journal of fungi (Basel, Switzerland) · 2021Article
- ATI-2307 Exhibits Equivalent Antifungal Activity inFrontiers in cellular and infection microbiology · 2021Article
- Pleiotropy and epistasis within and between signaling pathways defines the genetic architecture of fungal virulence.PLoS genetics · 2021Article
- Osteoarticular Cryptococcosis Successfully Treated with High-Dose Liposomal Amphotericin B Followed by Oral Fluconazole.Infection and drug resistance · 2021Article
- Decreasing fluconazole susceptibility of clinical South African Cryptococcus neoformans isolates over a decade.PLoS neglected tropical diseases · 2020Article
- The cost-effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa.Journal of the International AIDS Society · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundFluconazole is lifesaving for treatment and prevention of cryptococcosis; however, optimal dosing is unknown. Initial fluconazole doses of 100mg to 2000mg/day have been used. Prevalence of fluconazole non-susceptible Cryptococcus is increasing over time, risking the efficacy of long-established standard dosing. Based on current minimum inhibitory concentration (MIC) distribution, we modeled fluconazole concentration and area under the curve (AUC) relative to MIC to propose a rational fluconazole dosing strategy.
methodsFirst, we conducted a systematic review using MEDLINE database for reports of fluconazole MIC distribution against clinical Cryptococcus isolates. Second, we utilized fluconazole concentrations from 92 Ugandans who received fluconazole 800mg/day coupled with fluconazole's known pharmacokinetics to predict plasma fluconazole concentrations for doses ranging from 100mg to 2000mg via linear regression. Third, the fluconazole AUC above MIC ratio were calculated using Monte Carlo simulation and using the MIC distribution elucidated during the systemic review.
resultsWe summarized 21 studies with 11,049 clinical Cryptococcus isolates. MICs were normally distributed with geometric mean of 3.4 μg/mL, median (MIC50) of 4 μg/mL, and 90th percentile (MIC90) of 16 μg/mL. The median MIC50 trended upwards from 4 μg/mL in 2000-2012 to 8 μg/mL in 2014-2018. Predicted sub-therapeutic fluconazole concentrations (below MIC) would occur in 40% with 100mg, 21% with 200mg, and 9% with 400mg. AUC/MIC ratio >100 would occur in 53% for 400mg, 74% for 800mg, 83% for 1200mg, and 88% for 1600mg.
conclusionsCurrently recommended fluconazole doses may be inadequate for cryptococcosis. Further clinical studies are needed for rational fluconazole dose selection.
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