These modifications require fur- ther validation among patients who are hospitalized in both community-based and tertiary care hospitals, with particular attention to longer-term follow-up of patients rejected as hav- ing IE because they did not meet the minimal floor criteria for possible IE. The diagnosis of IE must be made as soon as possible to initiate appropriate empirical antibiotic therapy and to iden- tify patients at high risk for complications who may be best managed by early surgery. In cases with a high suspicion of IE based on either the clinical picture or the patient s risk fac- tor profile such as injection drug use, another focus of car- diovascular infection, including catheter-related bloodstream infections caused by S aureus, or a history of previous IE, the presumption of IE often is made before blood culture results are available. Identification of vegetations and incremental valvular insufficiency with echocardiography often com- pletes the diagnostic criteria for IE and affects the duration of therapy. Although the use of case definitions to establish a diagnosis of IE should not replace clinical judgment,46 the recently modified Duke criteria24 have been useful in both epidemiological and clinical trials and in individual patient management. Clinical, echocardiographic, and microbiologi- cal criteria (Tables 2 and 3) are used routinely to support a diagnosis of IE, and they do not rely on histopathological confirmation of resected valvular material or arterial embolus. If suggestive features are absent, then a negative echocardio- gram should prompt a more thorough search for alternative sources of fever and sepsis. In light of these important func- tions, at least 3 sets of blood cultures obtained from separate venipuncture sites should be obtained, with the first and last samples drawn at least 1 hour apart. 