Candida and Aspergillus species account for the large majority of fun- gal IE, and Candida-related IE is much more common than Blood cultures are ultimately positive in most cases caused by the former pathogen, whereas they are rarely positive in cases caused by the latter fungus. Thus, Aspergillus is a cause of culture-negative IE, and when this occurs, it is usually in a patient with a prosthetic cardiac A variety of other fungi, including endemic mycoses, can rarely cause IE and can involve both native and prosthetic valves. Noncardiac sites of metastatic infection often compli- cate fungal IE; this can include, for example, endophthalmitis in patients with candidal IE, which may require both systemic and intraocular antifungal therapy. Further guidelines are available from the Infectious Diseases Society of America for additional management aspects of several of the fungal patho- gens (http://www.idsociety.org/IDSA_Practice_Guidelines/). Despite aggressive combined medical and surgical inter- ventions and a younger cohort, mortality rates for fungal IE are unacceptably high. The survival rate for patients with mold-related IE is <20%. Historically, 2 treatment doctrines have prevailed in fungal IE despite the lack of prospective tri- als conducted to define the most appropriate therapy: Fungal IE is a stand-alone indication for surgical replacement of an infected valve; and amphotericin B, a fungicidal agent, is the initial drug of choice for fungal IE. Because of the alarming mortality rate associated with fungal IE and the availability of newer antifungal drugs, in particular fungicidal drugs like the echinocandins, a re-evaluation of these principles seems in order. If done, however, this will probably be based on anec- dotal experience and expert opinion rather than on clinical trial data because of the rarity of the syndrome. Baddour et al Infective Endocarditis in Adults 1465 A 2-phase treatment of fungal IE has evolved. 