Fungal Drug Resistance and Pharmacologic Considerations of Dosing Newer Antifungal Therapies

Recent advances in hematopoietic cell ­transplantation and a broadening array of salvage chemotherapy options have extended the survival of patients with hematological cancers, but can result in prolonged periods of immunosuppression and susceptibility to invasive ­fungal infections. Among these high-risk patient populations, systemic antifungal therapy is administered episodically or sometimes continuously for months or even years, increasing concerns for the development of antifungal resistance. As newer triazoles (voriconazole and posaconazole) and echinocandins (anidulafungin, caspofungin, and micafungin) have supplanted amphotericin B formulations as the preferred antifungal therapies for primary and secondary prophylaxis, pharmacokinetic variability inherent to the triazoles as well as emerging patterns of intrinsic and acquired antifungal resistance are becoming increasingly important factors in the long-term management of invasive fungal infections. In this chapter, we review recent data concerning antifungal drug resistance for these newer azoles and echinocandins, as well as key considerations in drug dosing.