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The association between fluconazole dose and MIC with mortality and persistence in candidemia

Nesrin Ghanem-Zoubi1, Majd Qasum2, Johad Khoury3

  • 1Infectious Diseases Institute, Rambam Health Care Campus, Ha-aliya 8 St, 3109601, Haifa, Israel. n_ghanem@rambam.health.gov.il.

European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology
|June 15, 2019
PubMed

Insights

Fluconazole dosing is not associated with outcomes in patients with low minimum inhibitory concentration (MIC) candidemia. However, careful dosing is needed for Candida species with high MICs to improve clinical outcomes.

Area of Science:

  • Medical Mycology
  • Infectious Diseases
  • Pharmacokinetics

Background:

  • Candidemia, a serious fungal infection, requires effective antifungal treatment.
  • Fluconazole is a common antifungal, but its efficacy can be influenced by drug exposure and fungal susceptibility.
  • Understanding the relationship between fluconazole exposure and clinical outcomes is crucial for optimizing patient care.

Purpose of the Study:

  • To investigate the association between fluconazole exposure parameters and clinical outcomes in patients with candidemia.
  • To analyze this association specifically in patients with Candida glabrata candidemia.
  • To determine if current fluconazole dosing strategies are adequate for all Candida species.

Main Methods:

  • Retrospective analysis of adult patients with fluconazole-susceptible candidemia from 2009-2017.
  • Assessment of fluconazole exposure parameters (AUC24/MIC) and clinical outcomes (30-day mortality, 14-day clinical failure).
  • Stratified analysis for Candida albicans, Candida glabrata, and Candida parapsilosis, with a focus on C. glabrata.

Main Results:

  • No significant association was found between fluconazole exposure parameters and 30-day mortality or 14-day clinical failure in the overall patient group.
  • For Candida glabrata, a higher AUC24/MIC was observed in 30-day survivors compared to non-survivors (p=0.008).
  • A trend towards lower fluconazole MIC values was noted in survivors with C. glabrata candidemia.

Conclusions:

  • Current fluconazole dosing regimens are not associated with clinical outcomes in candidemia caused by Candida species with low minimum inhibitory concentrations (MICs).
  • For Candida species exhibiting high MICs, particularly C. glabrata, optimizing fluconazole dosing is necessary to improve treatment efficacy.
  • Further research into individualized dosing strategies based on fungal susceptibility is warranted for better management of candidemia.
Keywords:
Area under curveCandidemiaFluconazoleMinimal inhibitory concentrationMortality

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