Voriconazole-refractory invasive aspergillosis

Korean J Intern Med. 2017 Sep;32(5):805-812. doi: 10.3904/kjim.2017.109. Epub 2017 Aug 24.

Abstract

Invasive aspergillosis (IA) is one of the most common life-threatening complications in immunocompromised patients. Voriconazole is currently the drug of choice for IA treatment. However, some patients with IA suffer clinical deterioration despite voriconazole therapy. Management of voriconazole-refractory IA remains challenging; no useful recommendations have yet been made. Voriconazole-refractory IA can be further categorized as disease attributable to misdiagnosis or co-infection with another mold; inadequate blood voriconazole blood; inadequate tissue drug concentrations attributable to angioinvasion; immune reconstitution inflammatory syndrome; or infection with voriconazole-resistant Aspergillus. Hence, when encountering a case of voriconazole-refractory IA, it is necessary to schedule sequential tests to decide whether medical treatment or surgical intervention is appropriate; to adjust the voriconazole dose via drug monitoring; to seek CYP2C19 polymorphisms; to monitor serum galactomannan levels; and to examine the drug susceptibility of the causative Aspergillus species.

Keywords: Aspergillosis; Aspergillus; Immunocompromised host; Therapy; Voriconazole.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Antifungal Agents / adverse effects
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / therapeutic use*
  • Aspergillus / drug effects*
  • Aspergillus / pathogenicity
  • Biopsy
  • Coinfection
  • Cytochrome P-450 CYP2C19 / genetics
  • Cytochrome P-450 CYP2C19 / metabolism
  • Diagnosis, Differential
  • Diagnostic Errors
  • Drug Monitoring
  • Drug Resistance, Fungal*
  • Female
  • Humans
  • Immunocompromised Host
  • Invasive Pulmonary Aspergillosis / diagnosis
  • Invasive Pulmonary Aspergillosis / drug therapy*
  • Invasive Pulmonary Aspergillosis / immunology
  • Invasive Pulmonary Aspergillosis / microbiology
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Pharmacogenomic Variants
  • Predictive Value of Tests
  • Tomography, X-Ray Computed
  • Voriconazole / adverse effects
  • Voriconazole / pharmacokinetics
  • Voriconazole / therapeutic use*

Substances

  • Antifungal Agents
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Voriconazole