Success rate and risk factors for failure of empirical antifungal therapy with itraconazole in patients with hematological malignancies: a multicenter, prospective, open-label, observational study in Korea

J Korean Med Sci. 2014 Jan;29(1):61-8. doi: 10.3346/jkms.2014.29.1.61. Epub 2013 Dec 26.

Abstract

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).

Keywords: Empirical Antifungal Therapy; Galactomannan Test; Hematological Malignancy; Itraconazole.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-alpha Demethylase Inhibitors / adverse effects
  • 14-alpha Demethylase Inhibitors / therapeutic use
  • Adolescent
  • Adult
  • Aged
  • Antifungal Agents / adverse effects
  • Antifungal Agents / therapeutic use*
  • Aspergillosis / complications
  • Aspergillosis / drug therapy*
  • Candidiasis / complications
  • Candidiasis / drug therapy*
  • Coccidioidomycosis / complications
  • Coccidioidomycosis / drug therapy
  • Febrile Neutropenia / complications
  • Febrile Neutropenia / drug therapy
  • Female
  • Galactose / analogs & derivatives
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / microbiology*
  • Humans
  • Itraconazole / adverse effects
  • Itraconazole / therapeutic use*
  • Male
  • Mannans / blood
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • 14-alpha Demethylase Inhibitors
  • Antifungal Agents
  • Mannans
  • galactomannan
  • Itraconazole
  • Galactose

Associated data

  • ClinicalTrials.gov/NCT01060462