How Do I Manage Refractory Invasive Pulmonary Aspergillosis

BACKGROUND:Invasive aspergillosis is associated with significant morbidity and mortality in patients with hematologic malignancies and hematopoietic cell transplant recipients. The prognosis is worse among patients who have failed primary antifungal treatment. OBJECTIVES:We aim to provide guidance on the diagnosis and management of refractory invasive pulmonary aspergillosis. SOURCES:Using PubMed we performed a review of original articles, meta-analyses, and systematic reviews. CONTENT:We discuss the diagnostic criteria for invasive pulmonary aspergillosis and the evidence on treatment of primary infection. We outline our diagnostic approach to refractory disease. We propose a treatment algorithm for refractory disease and discuss the role of experimental antifungal agents. IMPLICATIONS:For patients with worsening disease while on antifungal therapy, a thorough diagnostic evaluation is required to confirm the diagnosis of aspergillosis and exclude another concomitant infection. Treatment should be individualized. Current options include switching to another triazole, transitioning to a lipid formulation of amphotericin B, or using combination antifungal therapy.