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Pharmacokinetic Properties of Micafungin in Critically Ill Patients Diagnosed with Invasive Candidiasis

J M Boonstra1, K C van der Elst1, A Veringa1

  • 1University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands.

Antimicrobial Agents and Chemotherapy
|October 4, 2017
PubMed

Insights

Micafungin exposure is lower in critically ill patients than in healthy volunteers. Critically ill patients with lower SOFA scores and higher body weight may require adjusted micafungin dosing to prevent inadequate antifungal treatment.

Area of Science:

  • Pharmacology
  • Critical Care Medicine
  • Infectious Diseases

Background:

  • Invasive candidiasis (IC) has a high attributable mortality rate (30-40%) in intensive care units (ICUs).
  • Physiological changes in critically ill patients can alter micafungin pharmacokinetics, potentially necessitating dose adjustments.
  • Understanding micafungin exposure is crucial for optimizing treatment of invasive candidiasis in the ICU.

Purpose of the Study:

  • To determine micafungin pharmacokinetic parameters in critically ill patients.
  • To assess the probability of achieving therapeutic targets for micafungin in this population.
  • To identify patient factors influencing micafungin exposure and treatment efficacy.

Main Methods:

  • Micafungin plasma concentrations were measured to estimate pharmacokinetic properties.
  • Minimum Inhibitory Concentration (MIC) values for Candida isolates were determined.
  • Pharmacokinetic/pharmacodynamic (PK/PD) targets, specifically the AUC/MIC ratio, were assessed in 19 ICU patients.

Main Results:

  • Critically ill patients exhibited significantly lower median AUC0-24 values compared to healthy volunteers (89.6 vs. 152.0 and 134.0 mg·h/L).
  • All Candida isolates were susceptible to micafungin (median MIC = 0.016 mg/L).
  • 17.6% of patients with proven IC did not meet the target AUC/MIC ratio of 5,000; lower exposure was linked to body weight.

Conclusions:

  • Micafungin exposure is reduced in critically ill patients, potentially impacting treatment effectiveness.
  • Patients with lower Sequential Organ Failure Assessment (SOFA) scores (<10) and body weight >100 kg receiving 100 mg daily may be at risk for inadequate exposure.
  • Dosing adjustments for micafungin may be necessary in specific ICU patient subgroups to ensure optimal antifungal therapy.
Keywords:
critically illinvasive candidiasismicafunginpharmacokinetics

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