The rationale of combination antifungal therapy in severely immunocompromised patients: empiricism versus evidence-based medicine

Curr Opin Infect Dis. 2006 Aug;19(4):380-5. doi: 10.1097/01.qco.0000235166.16421.e5.


Purpose of review: Despite expansion of the antifungal armamentarium over the past decade, the mortality rate for invasive fungal infections remains high in severely immunocompromised patients. Furthermore, in recent years, difficult-to-treat invasive infections caused by rare molds and yeasts have emerged in high-risk patients receiving antifungal prophylaxis or empirical treatment. Antifungal combinations are increasingly used in clinical practice to improve outcomes for refractory mycoses because of the suboptimal efficacy of current antifungal agents. Herein we review recent advances in the area of antifungal combinations in high-risk patients to separate empiricism from evidence-based medicine.

Recent findings: Thus far, the benefits of combination antifungal therapy have been difficult to prove for invasive fungal infections other than cryptococcal meningitis. The recent introduction of a new class of antifungal agents (the echinocandins) and extended-spectrum triazoles has rejuvenated interest in studying those combinations for difficult-to-treat aspergillosis, as recent observational studies show promise.

Summary: In view of the evolving epidemiology of invasive fungal infections, combination antifungal therapy could be most valuable in preemptive management of carefully selected high-risk patients; however, this should be studied in appropriate trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antifungal Agents / administration & dosage*
  • Aspergillosis / drug therapy
  • Aspergillosis / immunology
  • Candidiasis / drug therapy
  • Candidiasis / immunology
  • Drug Therapy, Combination
  • Empiricism
  • Evidence-Based Medicine
  • Humans
  • Immunocompromised Host*
  • Mycoses / drug therapy*
  • Mycoses / immunology*


  • Antifungal Agents