Endocarditis and Other Intravascular Infections

Native Valve Endocarditis

The most important factor in the pathogenesis of endocarditis is disruption of vascular endothelium, typically caused by turbulent blood flow or foreign body (e.g., a CVC) in contact with the endocardium, or both. Turbulence generally results from a communication between an area of high pressure and an area of low pressure, such as flow through a ventricular septal defect or regurgitation through an incompetent valve. ^, Erosion of endothelium occurs, facilitating deposition of platelet-fibrin thrombi on the mural surface or on an abnormal valve on the low-pressure side.

Important pathogen factors include an organism’s ability to produce bloodstream infection (BSI) (bacteremia or fungemia), as well as the presence of microbial adhesins. The peptidoglycan surface of oral streptococci facilitates adherence to endothelial cells . Similarly, S. aureus binds to collagen, fibronectin, laminin, vitronectin, and fibrinogen. ^, Microbial surface components that recognize adhesive matrix molecules likely are virulence factors of S. aureus . Patients with S. aureus endocarditis have higher serum levels of adhesin molecules than patients with S. aureus BSI without endocarditis. The bacterial adhesins of CoNS are less well understood but may be capsular polysaccharides.

The rate of bacteremia associated with common events and medical procedures is shown in Table 37.3 . Although dental procedures, such as drainage of an abscess, gingival surgery, and tooth extraction, are particularly likely to cause bacteremia, transient bacteremia after common daily activities such as tooth brushing is far more frequent. Thus, an antecedent event clearly responsible for endocarditis is only rarely identified.

Right-sided endocarditis can be due to a CVC extending into the structurally normal heart. In an experimental model in rabbits, endocarditis only develops when bacteremia is preceded by placement of an intravenous polyethylene catheter across the tricuspid valve into the right ventricle. The catheter acts as a foreign body, abrading endocardial and valvular surfaces and resulting in sterile vegetations that serve as a nidus for infection.

Postoperative Endocarditis

The pathogenesis of endocarditis occurring ≤6 months (early) and >6 months after surgery (late) differ. In the early postoperative period, denuded endothelium and exposed sutures are adjacent to prosthetic material; thrombi can form at these sites with fibrin deposition. Endocarditis can result if bacteremia or fungemia follows, potentially as a result of contamination of intravenous solutions, the cardiac bypass pump, a surgical site, CVC, exposed pacemaker wires, or exposed intracardiac catheters. In addition, bacterial or fungal contamination of the operative site can be caused by infected homografts or the colonized hands of healthcare personnel. Late postoperative endocarditis occurs after re-endothelialization of cardiac and vascular surfaces, with pathophysiology more akin to native valve endocarditis. Pacemaker wires do not become re-endothelialized. Residual intracardiac lesions at the site of prior surgical repair leads to inadequate re-endothelialization and an ongoing higher risk of endocarditis. Emerging literature suggests that there may be differential risks of infective endocarditis depending on the surgical approach, with increased incidence of infective endocarditis when pulmonary valves have been replaced using a transcatheter approach rather than an open surgical approach.

Pacemaker and Ventricular Assist Device Infections

Placement of cardiovascular implantable electronic devices (pacemaker or cardioverter-defibrillator) in children and adolescents is increasing. ^, Contamination during placement and infection of the pulse-generator pocket can result after device placement. Endocarditis is relatively rare and accounts for approximately 10% of implantable device-associated infections, although younger patients may have more frequent lead-wire infections than older patients. ^, Complete removal of the device is recommended when a deep pocket infection occurs because of the high risk for relapse and for contaminating the intravascular portion of the device. ^,

Ventricular assist devices (VADs) are increasingly being used to support patients awaiting heart transplantation in the pediatric population. Although data are limited, the rate of infectious complications is high, occurring in 18%–59% of patients, and complications include surgical site infections, BSIs, and endocarditis presenting as relapsing BSI. Management of VAD-related infections is highly complex owing to the critical need for the device, presence of intravascular and intracardiac foreign material, and high risk for relapse.

Pathologic Lesions

Gross and Microscopic Findings

Vegetations can be single or multiple and vary in size from 1–2 mm to several centimeters ( Figs. 37.1 and 37.2 ). Endocarditis can destroy the underlying valve or perforate valve leaflets; rupture the chordae tendineae, papillary muscle, or interventricular septum; or lead to abscess of the valve ring. Healing can result in fibrosis and calcification. Myocardial abscesses and pericarditis also can be present. Vegetations consist of fibrin, platelets, and bacteria. Neutrophils and red blood cells also can be seen ( Fig. 37.3 ).

Symptoms

Classically, the clinical manifestations of endocarditis were categorized as either subacute, generally manifesting with a prodrome of moderate illness and nonspecific symptoms for several weeks, or acute, with a short prodrome and a sepsis-like presentation. However, individual cases can have mixed features, and the presentation does not always predict the infecting microorganism.

Common symptoms of endocarditis in children are shown in Table 37.4 . The subtle and nonspecific nature of symptoms can delay diagnosis for weeks. ^, Endocarditis should be suspected in patients with (1) congenital heart disease or other risk factors for endocarditis with unexplained fever and fatigue (or anemia) that can remit temporarily when oral antibiotics are prescribed; (2) congenital heart disease with new onset of congestive heart failure or conduction abnormalities, especially if accompanied by fever; (3) abrupt onset of septicemia or appearance of vascular lesions in soft tissues or mucous membranes; and (4) a structurally normal heart with blood cultures persistently positive after optimal treatment is instituted or after removal of a CV.

Vegetations, especially those on valve leaflets, can break off into the circulation. Significant morbidity can result from infectious emboli to the lungs (right-sided endocarditis) or to the central nervous system, kidney, spleen, and extremities (left-sided endocarditis). Embolic events can be the predominant clinical feature in some cases. ^, Patients with fever and unexplained neurologic symptoms or with apparent pulmonary emboli, particularly if multifocal, should be evaluated promptly for endocarditis.

Physical Examination

Table 37.4 shows the frequency of physical findings in endocarditis. It may be difficult to discern subtle changes in an existing murmur or detection of a new murmur in a febrile child with tachycardia. In patients with rapidly progressing infection, physical examination may not reveal the classic signs of endocarditis, and thus endocarditis is suspected because of underlying heart disease or persistently positive blood cultures or embolic events, including splinter hemorrhages (i.e., dark linear streaks in the nail beds). Signs due to deposition of immune complexes composed of bacterial antigens, antibodies, and complement in peripheral tissue are rare in children. These include Osler nodes, which are small (2−15 mm), painful, purplish lesions in the pulp of the fingers or toes that persist for hours or days; Janeway lesions, that is, painless hemorrhagic macular plaques on the palms or soles due to emboli that persist for days; or Roth spots, which are small hemorrhagic retinal lesions with a pale center, usually near the optic disk.