**2. Infective endocarditis and septic embolism: general clinical, diagnostic and treatment considerations**

#### **2.1. General clinical and microbiological considerations**

The estimated crude annual incidence of IE is approximately 1 case per 33,000 population, with peak incidence among men between the ages of 70 and 80 years (approximately 1 in 6,900) [1]. Infective endocarditis is a predominantly male disease (50–65% patients) with mean age at the time of presentation between 52 and 63 years, depending on the causative microorganism [1, 3]. Major risk factors for IE include underlying heart disease, cardiac surgery and interventional procedures, prosthetic valve, intravenous drug use, immunosuppression, dental infections, and previous infective endocarditis [1, 3, 5]. Alimentary, genitourinary, respiratory tract, orthopedic, and skin infections, as well as pregnancy-related infection events have also been associated with IE, although far less commonly [3, 6]. Mortality ranges between 6% and 30%, again depending on patient factors and the microorganism(s) involved [1, 3]. Of note, mortality rate was noted to be higher (20%) among patients with IE who experienced embolic or "metastatic" events when compared to individuals without such occurrences (12%) [4].

Clinical presentation of IE involves the development of fever in >90% of cases, with approximately one out of three affected patients experiencing congestive heart failure [1]. Heart murmurs can be present, but may be more reflective of primary valvular disease rather than IE itself [7]. Elevated serum creatinine suggesting renal failure may be present in >25% of cases, and approximately 10% of patients develop septic shock [1]. Rarely, associated life-threatening events such as cardiac tamponade have been reported [8]. According to large clinical series on IE, the most commonly encountered bacteria include *Staphylococci* (19–29% cases), *Streptococci* (44–48%), *Enterococci* (8–19%), Gram-negative organisms, (5–7%), polymicrobial occurrences (0.7–3%), with 5–10% of cases having no microorganisms identified (also known as "culture negative" endocarditis) [1, 3]. Of importance, nosocomial/iatrogenic cases of IE are more likely to be associated with staphylococcal infection when compared to community-acquired IE (35% versus 21%, respectively) [1].

#### **2.2. Pathophysiologic considerations**

Septic embolism is most commonly associated with IE, septic thrombophlebitis, periodontal and various systemic infections, as well as central venous catheter and implanted device infections [2]. The combination of aging population, implantable device miniaturization, and the emergence of multi-morbidity have all synergistically contributed to the increased risk of both IE and SE [2, 9]. Thrombogenic characteristics associated with intravascular infections, combined with the relative lack of antibiotic efficacy to clear bloodstream infections, result in elevated risk of SE [10]. According to Millaire et al. [4], embolic events may occur in >50% of IE cases. Fortunately, such events are not associated with significant attributable mortality when properly managed [4]. Further focusing on the cardiac etiology of SE, one of the largest series reported that embolization to the central nervous system was seen in approximately 20% cases of mitral valve IE, 15% cases of aortic valve IE, and 18% combined cases of aortic and mitral IE [1]. When examining right-sided endocarditis, 68% of cases were associated with pulmonary embolization [1]. Finally, it is important to recognize that IE is distinct from nonbacterial thrombotic endocarditis—a pathologic entity that can also result in distal embolization and is beyond the scope of the current chapter [11].

#### **2.3. Septic embolization by anatomic location**

index of suspicion are required as the diagnosis of IE and SE is not based on a single test but rather on the combination of clinical findings and diagnostic studies. Microbiologic studies guide antimicrobial therapy. Advanced imaging, including computed tomography (CT) and magnetic resonance imaging (MRI), is used to identify both the extent and location(s) of postembolic infarcts or abscesses. Surgical management, both cardiac and noncardiac, is beyond the scope of the current chapter and is discussed elsewhere in this comprehensive

**2. Infective endocarditis and septic embolism: general clinical, diagnostic**

The estimated crude annual incidence of IE is approximately 1 case per 33,000 population, with peak incidence among men between the ages of 70 and 80 years (approximately 1 in 6,900) [1]. Infective endocarditis is a predominantly male disease (50–65% patients) with mean age at the time of presentation between 52 and 63 years, depending on the causative microorganism [1, 3]. Major risk factors for IE include underlying heart disease, cardiac surgery and interventional procedures, prosthetic valve, intravenous drug use, immunosuppression, dental infections, and previous infective endocarditis [1, 3, 5]. Alimentary, genitourinary, respiratory tract, orthopedic, and skin infections, as well as pregnancy-related infection events have also been associated with IE, although far less commonly [3, 6]. Mortality ranges between 6% and 30%, again depending on patient factors and the microorganism(s) involved [1, 3]. Of note, mortality rate was noted to be higher (20%) among patients with IE who experienced embolic or "metastatic" events when compared to individuals without such occurrences (12%) [4].

Clinical presentation of IE involves the development of fever in >90% of cases, with approximately one out of three affected patients experiencing congestive heart failure [1]. Heart murmurs can be present, but may be more reflective of primary valvular disease rather than IE itself [7]. Elevated serum creatinine suggesting renal failure may be present in >25% of cases, and approximately 10% of patients develop septic shock [1]. Rarely, associated life-threatening events such as cardiac tamponade have been reported [8]. According to large clinical series on IE, the most commonly encountered bacteria include *Staphylococci* (19–29% cases), *Streptococci* (44–48%), *Enterococci* (8–19%), Gram-negative organisms, (5–7%), polymicrobial occurrences (0.7–3%), with 5–10% of cases having no microorganisms identified (also known as "culture negative" endocarditis) [1, 3]. Of importance, nosocomial/iatrogenic cases of IE are more likely to be associated with staphylococcal infection when compared to community-acquired IE (35%

Septic embolism is most commonly associated with IE, septic thrombophlebitis, periodontal and various systemic infections, as well as central venous catheter and implanted device

textbook.

**and treatment considerations**

144 Contemporary Challenges in Endocarditis

versus 21%, respectively) [1].

**2.2. Pathophysiologic considerations**

**2.1. General clinical and microbiological considerations**

When examining the anatomic distribution of nonpulmonary SE in the setting of IE, the most commonly affected organs and organ systems included the central nervous system (48–65%), extremities (30%), spleen (19–32%), and kidney (6–14%) [1, 4, 12]. Less commonly affected structures/organs included the lung (14%), coronary vessels (6%), the liver (3–11%), bone and joint structures (11%), iliac arterial system (6%), and mesenteric arteries (3%) [1, 2, 4]. From anatomic standpoint, a special and more "diffuse" category of embolic events includes musculoskeletal manifestations, which are thought to occur in as many as 44% of cases of SE [13]. Due to their self-limiting nature and nonspecific manifestations (e.g., arthralgias, myalgias, back pain, arthritis), this category of events is often under-reported and tends to be

**Figure 1.** Diagram showing the anatomic distribution of septic emboli in the setting of infectious endocarditis. Compiled from multiple literature sources [1, 2, 4, 12–14].

neglected [14]. **Figure 1** summarizes the anatomic distribution of septic emboli in the setting of IE [1, 2, 4, 12–14]. Of note, anatomic distribution of septic emboli associated with infective endocarditis (48–65% cerebral, 35–52% noncerebral [1, 2, 4]) approximates that of valvular atrial fibrillation (56–63% cerebral, 38–44% noncerebral [15, 16]) suggesting that structural anatomic factors play a role in the pathophysiology of emboli originating from cardiac valves [16–18].
