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Breakthrough invasive fungal infections in neutropenic patients after prophylaxis with itraconazole

A Glasmacher1, C Hahn, C Leutner

  • 1Department of Internal Medicine, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.

Mycoses
|November 5, 1999
PubMed

Insights

Patients receiving antifungal prophylaxis with itraconazole for haematological malignancies experienced breakthrough fungal infections when drug levels were below 500 ng/mL. Lower itraconazole concentrations correlated with fatal outcomes in these neutropenic patients.

Area of Science:

  • Mycology
  • Hematology
  • Pharmacology

Background:

  • Invasive fungal infections (IFIs) pose a significant risk to neutropenic patients with hematological malignancies.
  • Antifungal prophylaxis is a common strategy to prevent IFIs in this vulnerable population.
  • Itraconazole is frequently used for prophylaxis, but breakthrough infections can still occur.

Purpose of the Study:

  • To analyze the incidence and outcomes of IFIs in neutropenic patients undergoing antifungal prophylaxis with itraconazole.
  • To investigate the relationship between itraconazole trough concentrations and the occurrence of IFIs.
  • To determine if itraconazole levels are associated with the mortality of IFIs in this patient group.

Main Methods:

  • A retrospective analysis of 20 neutropenic patients with hematological malignancies who developed IFIs during itraconazole prophylaxis (September 1994 - December 1998).
  • Comparison of itraconazole trough concentrations in patients with IFIs versus a control group of 150 leukemia patients without IFIs.
  • Measurement of itraconazole trough concentrations using high-performance liquid chromatography (HPLC).

Main Results:

  • Eighteen of 20 patients developed pulmonary mold infections; two had disseminated yeast infections.
  • Patients with IFIs had significantly lower itraconazole trough concentrations (<500 ng/mL) compared to controls (median 48% vs. 100%, P=0.039).
  • Fatal IFIs were associated with significantly lower pre-infection itraconazole concentrations (median 120 ng/mL) compared to non-fatal cases (median 690 ng/mL, P=0.039).

Conclusions:

  • Itraconazole trough concentrations below 500 ng/mL are associated with a higher risk of breakthrough IFIs in neutropenic patients with hematological malignancies.
  • Lower itraconazole levels correlate with increased mortality from IFIs.
  • Therapeutic drug monitoring of itraconazole may be crucial for optimizing prophylaxis and improving outcomes in high-risk patients.

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