Echinocandin activity against Aspergillus spp. and the importance of pharmacodynamics

Echinocandins represent a safe and well tolerated option for the therapy of invasive aspergillosis in patients who are unable to tolerate other agents or have refractory disease. In vitro and animal model data provide useful insights into the activity, appropriate dose, and potential role of these agents in invasive aspergillosis. These studies reveal a potentially concerning lack of tissue sterilization when echinocandins are used as monotherapy but clearly show improved survival with increasing doses. Furthermore pharmacodynamic studies suggest that echinocandin doses currently in widespread clinical use may optimize outcomes in invasive aspergillosis. A paucity of clinical data exists examining these agents as monotherapy for invasive aspergillosis and virtually no clinical data exists for using these agents as primary therapy. Further data examining the role of echinocandin monotherapy for invasive aspergillosis is unlikely to be forthcoming in the foreseeable future due to several factors including the aforementioned issues, the relatively small number patients with this infection, and the belief that these agents are potentially best used as part of combination therapy regimens for invasive aspergillosis.