For patients with culture-negative PVE, cover- age for staphylococci, enterococci, and aerobic Gram-negative bacilli is reasonable if onset of symp- toms is within 1 year of prosthetic valve placement (Class IIa; Level of Evidence C). 6. If symptom onset is >1 year after valve placement, then IE is more likely to be caused by staphylococci, VGS, and enterococci, and antibiotic therapy for these potential pathogens is reasonable (Class IIa; Level of Evidence C). 7. If subsequent blood culture results or other labora- tory methodologies define a pathogen, then empiri- cal therapy should be revised to focused therapy that is recommended for the specific pathogen iden- tified (Class I; Level of Evidence C). Fungi Fungal IE is rare but can develop in a wide range of The well-recognized risk factors associated with fungal IE (eg, IDU and immunocompromised state) have become less prevalent compared with the presence of a car- diovascular device, including central venous catheters, perma- nent pacemakers and defibrillators, and prosthetic valves.240 246 Fungal IE has been recognized as a cause of early PVE, but a case series from a single medical center demonstrated that 43% of these cases had symptom onset >1 years after pros- thetic valve placement.242 In contrast to the expected older age predilection for the development of IE, patients with fungal IE have been younger, which was somewhat unanticipated, con- sidering the low prevalence of IDU among the cohort. 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. 