**2.4. Diagnostic considerations**

Diagnosis of SE requires high index of clinical suspicion, combined with accurate identification and recognition of IE as a source. In the setting of native heart valves, trans-thoracic echocardiography (TTE) should be performed as an initial screening test [19]. If results of the TTE are negative, IE can usually be ruled out if Duke criteria suggest low probability [20, 21]. However, if Duke criteria suggest high suspicion of IE, or if TTE is positive or suspicious for IE, or the patient has a prosthetic valve, the next diagnostic step should be the performance of transesophageal echocardiography (TEE) [7, 19–21]. If the TEE is positive, the diagnosis is confirmed. However, if negative, the test can be repeated in 1–2 weeks if clinical suspicion continues to be high [19]. If the above diagnostic steps continue to produce negative results, alternative diagnosis should be entertained.

Multiple, repeated blood culture determinations are often required to identify the causative organism. Although microbiological studies provide critical information regarding targeted antibiotic therapy in IE, results are not always immediately available or universally accurate [22, 23]. Among more recent developments, real-time polymerase chain reaction (PCR) is more sensitive and specific in addition to providing clinically relevant results quickly [24]. Initial antimicrobial coverage should be broad, and once the involved microorganism is identified and antibiotic susceptibilities are known, the therapy can be appropriately narrowed to optimize long-term management. When SE is suspected, advanced imaging (CT and/or MRI) constitutes the cornerstone of confirmatory testing [2, 14, 25, 26].

#### **2.5. Therapeutic considerations**

Infective endocarditis complicated by SE requires a multidisciplinary, multimodality therapeutic approach. As outlined in previous sections, broad-spectrum antibiotic management is the most important initial step in management of both IE and SE. Once the offending microorganism is confirmed by microbiological testing, antibiotic coverage should be narrowed according to established sensitivity data. The decision to proceed with cardiac surgical therapy of IE is a complex one, most indications are not absolute, and pertinent decision-making is discussed elsewhere in this text. When cardiac surgery is indicated, early intervention has been associated with decreased all-cause mortality (including deaths following SE) due largely to the lower risk of subsequent systemic embolization [27]. When SE is present, the type and location of emboli guides the treatment strategy. Other surgical and interventional procedures may be utilized to treat complications resulting from SE, including vascular or endovascular interventions for arterial aneurysms [2, 28, 29], percutaneous drainage of abscesses [2], or organ resections (i.e., splenectomy or bowel resection) for infarctions and/or refractory infections [30, 31].
