Antifungal chemotherapy: advances and perspectives

Abstract

Invasive fungal infections have emerged as important causes of morbidity and mortality in immunocompromised patients. In response to this challenge, the field of antifungal chemotherapy has considerably expanded. Fluconazole and itraconazole, introduced in the late 1980s, were the first durably useful alternatives to amphotericin B deoxycholate. The clinical development of the lipid formulations of amphotericin B, and, more recently, that of novel echinocandin derivatives and improved antifungal triazoles each represent milestones in antifungal drug research that have further amplified our therapeutic options. Major progress has been made in harmonising disease definitions, in defining the paradigms of antifungal intervention, and in designing and implementing clinical trials. Standardised methods for in vitro susceptibility testing of yeasts and filamentous fungi have become available, and pharmacodynamic concepts have entered preclinical and clinical drug development. This article reviews the evolution of therapeutic options over the past decade, advances in chemoprevention and empirical antifungal therapy, progress in early diagnosis and pre-emptive therapy, the promise of the new echinocandins and second generation triazoles, as well as perspectives for combination therapies and adjuvant immunoreconstitution. Invasive fungal infections will remain a frequent and important complication of modern medicine; the current momentum in the field of laboratory and clinical antifungal drug research provides hope for substantial progress in prevention and management of these life-threatening infections in the near future.