Correlation of the MIC and dose/MIC ratio of fluconazole to the therapeutic response of patients with mucosal candidiasis and candidemia

Rodríguez-Tudela, Juan L.; Almirante, Benito; Rodríguez-Pardo, Dolors; Laguna, Fernando; Donnelly, J. Peter; Mouton, Johan W.; Pahissa, Albert; Cuenca-Estrella, Manuel

doi:10.1128/aac.00296-07

Cited by 137Antifungal resistance and susceptibilityAntibiotics Pharmacokinetics and EfficacyFungal Infections and Studies

Correlation of the MIC and dose/MIC ratio of fluconazole to the therapeutic response of patients with mucosal candidiasis and candidemia

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Rodríguez-Tudela, Juan L., Almirante, Benito, Rodríguez-Pardo, Dolors, Laguna, Fernando, Donnelly, J. Peter, Mouton, Johan W., Pahissa, Albert, Cuenca-Estrella, Manuel·2007·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.00296-07PMC PMC2043257

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Abstract

We report on the correlation of the outcomes for two cohorts of patients who had been treated for candidemia (126 episodes) or oropharyngeal candidiasis (110 episodes) with various doses of fluconazole and the MIC of fluconazole obtained by using the EUCAST standard for fermentative yeasts. Of 145 episodes caused by an isolate with a fluconazole MIC ≤2 mg/liter, 93.7% (136 of 145) responded to fluconazole treatment. The response for those infected with a strain with a MIC of 4 mg/liter was 66% but reached 100% when the dose was greater than 100 mg/day, whereas the response for those infected with strains with MICs ≥8 mg/liter was only 12%. Hence, a MIC of 2 mg/liter or 4 mg/liter was able to predict successful treatment. A cure rate of 93.9% (140 of 149) was achieved when the dose/MIC ratio was ≥100 but fell to 14.6% (16 of 109) when the ratio was less. The dose/MIC required to achieve a response rate of 50% (the 50% effective concentration) was 43.7 for the cohort of patients with oropharyngeal candidiasis. Classification and regression analysis indicated that a dose/MIC of 35.5 was the threshold for the prediction of cure or failure. However, an increase in exposure above this threshold further increased the probability of cure, and all patients were cured when the dose/MIC exceeded 100. Monte Carlo simulations showed a probability of target attainment of 99% at MICs ≤2 mg/liter and a pharmacodynamic target of a dose/MIC ratio of 100, which was equivalent to an unbound fraction of the fluconazole area under the curve versus the MIC of 79.

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A more contemporary analysis in mucosal candidiasis found clinical efficacy of 92% with fluconazole AUC/MIC greater than 25 and only 9% with values less than 25.
“A more contemporary analysis in mucosal candidiasis corroborated the earlier findings, with clinical efficacy of 92% with an AUC/MIC greater than 25 and only 9% with values less than 25.”
From Fungal Sepsis: Optimizing Antifungal Therapy in the Critical Care Setting (2011) · cites this paper as [147]

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Self-citation

Authors: Rodríguez-Tudela, J. L., Almirante, B., Rodríguez-Pardo, D., Laguna, F., Donnelly, J. P., Mouton, J. W., Pahissa, A., & Cuenca-Estrella, M.
Affiliations: Servicio de Micologia, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid
Vall d'Hebron Hospital Universitari (ES)
Servicio de Enfermedades Infecciosas, Hospital Universitario Valle de Hebrón, Barcelona
Carlos III Hospital (ES)
Radboud University Nijmegen (NL)
Canisius-Wilhelmina Ziekenhuis (NL)
ORCID: Almirante, Benito
Laguna, Fernando
Donnelly, J. Peter
Mouton, Johan W.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2007-10
Volume: 51
Issue: 10
Pages: 3599-3604
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.00296-07
PMC: PMC2043257
OpenAlex: W2136501331
Cited by: 137
References: 32
Citations by year: 2026: 2 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 13 · 2020: 8 · 2019: 4 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 11 · 2014: 10 · 2013: 8 · 2012: 7
FWCI: 6.92
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords: fluconazole, antifungal susceptibility, candidemia, oropharyngeal candidiasis, mucosal candidiasis, therapeutic drug monitoring, pharmacodynamic target attainment, probability of target attainment, treatment response prediction, Monte Carlo simulation
MeSH terms: Adolescent, Adult, Aged, Aged, 80 and over, Antifungal Agents, Candida, Candidiasis, Candidiasis, Oral, Dose-Response Relationship, Drug, Female, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Monte Carlo Method, Mucous Membrane, Oropharynx, Regression Analysis, Spain, Cohort Studies, HIV Infections, Fluconazole, Fungemia, Treatment Outcome, Area Under Curve

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Correlation of the MIC and dose/MIC ratio of fluconazole to the therapeutic response of patients with mucosal candidiasis and candidemia

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