title: The rationale of combination antifungal therapy in severely immunocompromised patients: empiricism versus evidence-based medicine.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, USA.
authors.forename: Georgios
authors.initials: G
authors.lastname: Chamilos
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Kontoyiannis
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage*; D001228:Aspergillosis / Q000188:drug therapy / Q000276:immunology; D002177:Candidiasis / Q000188:drug therapy / Q000276:immunology; D004359:Drug Therapy, Combination; D019348:Empiricism; D019317:Evidence-Based Medicine; D006801:Humans; D016867:Immunocompromised Host; D009181:Mycoses / Q000188:drug therapy* / Q000276:immunology*
chemical_list: D000935:Antifungal Agents