Echinocandins: addressing outstanding questions surrounding treatment of invasive fungal infections.

PURPOSE: Recent in vitro and clinical data addressing outstanding issues regarding the selection, dosing, and monitoring of echinocandins for the treatment of invasive fungal infections (IFIs) are reviewed. SUMMARY: The echinocandins (caspofungin, micafungin, and anidulafungin) are attractive treatment options for the treatment of select IFIs, most notably invasive candidiasis and treatment-refractory invasive aspergillosis. A literature review of English-language articles published between January 2007 and May 2010 was performed using the terms caspofungin, micafungin, anidulafungin, and echinocandin. In vitro, in vivo, and both pediatric and adult clinical studies and case reports were included. The challenges to establish meaningful interpretive criteria for in vitro testing of yeasts continue to persist, as do the establishment of the clinical relevancy of both the reduced in vitro susceptibilities to Candida parapsilosis and the paradoxical growth of Candida species at higher dosages. Despite increasing use of these agents and reports of breakthrough infections, echinocandins have continued to maintain potency against a broad spectrum of Candida and Aspergillus species. Recent in vitro studies also support the excellent activity of echinocandins against Candida biofilms. While recent published studies have better defined dosing in special populations (such as pediatric patients and those with organ dysfunction), attempts to increase efficacy by dosage intensification have been unsuccessful. Several pharmacoeconomic studies have been performed in attempts to justify the high acquisition costs of these drugs. In general, these studies found that echinocandins may be cost-effective for such indications. CONCLUSION: Available in vitro data, animal studies, and clinical studies do not clearly differentiate agents in the echinocandin class. Clinical data continue to support the use of echinocandins as a safe and well-tolerated treatment option for candidemia and invasive aspergillosis.

Duke Scholars

Author Richard Howard Drew Medicine, Infectious Diseases