Infective endocarditis

Definition and Epidemiology

• Infective endocarditis is defined as a microbial infection of the endothelial or endocardial surface of the heart, most commonly involving the native heart valves, prosthetic valves, mural endocardium, and the endothelium of blood vessels (infective endarteritis).
• It may also involve intracardiac foreign materials such as surgical shunts, pericardial patches, and percutaneous devices.
• The incidence of pediatric infective endocarditis ranges from 0.34 to 0.64 cases per 100,000 children per year.
• In developed countries, congenital heart disease serves as the overwhelming predisposing factor for infective endocarditis.
• High-risk patient populations include those with prosthetic cardiac valves, unrepaired cyanotic congenital heart disease (including palliative shunts and conduits), previous history of infective endocarditis, and cardiac transplant recipients who develop valvulopathy.
• Patients who have undergone complete surgical or catheter-based repair of a congenital heart defect with prosthetic material or devices remain at high risk during the first six months after the procedure, or lifelong if there is a residual defect adjacent to the prosthetic patch or device.
• Infective endocarditis is exceedingly rare in healthy infants; in this age group, it is predominantly associated with indwelling central venous catheters, prematurity, or following open-heart surgery.
• Lesions characterized by high-velocity turbulent blood flow, such as restrictive ventricular septal defects, aortic stenosis, coarctation of the aorta, and tetralogy of Fallot, carry a significantly elevated risk for endocarditis.
• In contrast, lesions with little or no turbulent flow, such as isolated secundum atrial septal defects, are not associated with an increased risk of infective endocarditis.

Pathophysiology

• The pathogenesis of infective endocarditis relies on a complex interaction between pathogenic microorganisms, the host immune system, and the valvular endothelium.
• The initial event requires damage to the valvular endothelium, which is typically caused mechanically by unphysiological, high-velocity turbulent blood flow (jet lesions).
• Endothelial damage leads to the exposure of underlying matrix proteins, initiating a thrombogenic response where fibrin and platelets deposit to form a sterile vegetation, termed nonbacterial thrombotic endocarditis (NBTE).
• Concurrently, activated monocytes produce tissue factor, initiating the coagulation cascade and further fibrin deposition.
• When a patient experiences transient bacteremia—frequently originating from the mucosal surfaces of the oropharynx, gastrointestinal tract, or genitourinary tract during routine daily activities like tooth brushing or chewing—the circulating bacteria adhere to and colonize the sterile NBTE.
• Certain bacteria, such as Staphylococcus aureus, possess a high potency for adhering to and invading endothelial cells independently, enabling them to actively facilitate coagulation and increase their own pathogenicity.
• Once bacteria attach to the fibrin-platelet matrix, they rapidly proliferate and embed within a biofilm, allowing them to escape elimination by the host's immune system and rendering them relatively inaccessible to antimicrobial agents.

Microbiology

Clinical Manifestations

• The clinical features of infective endocarditis are driven by four key pathophysiological mechanisms: continuous bacteremia, local valvular destruction, systemic embolization, and the host's immunological response.
• Fever is the most ubiquitous symptom, present in 80% to 90% of cases, and may persist for several weeks before a definitive diagnosis is made.
• Fever is frequently accompanied by generalized, nonspecific symptoms including fatigue, malaise, chills, night sweats, significant loss of appetite, weight loss, myalgia, and arthralgia.
• Progressive valvular destruction and the resulting regurgitant lesions can lead to acute hemodynamic deterioration, culminating in severe congestive heart failure and cardiogenic shock.
• Right-sided endocarditis (involving the tricuspid or pulmonary valves) frequently results in pulmonary thromboembolism, manifesting as cough, chest pain, hypoxemia, hemoptysis, pneumonitis, or septic lung abscesses.
• Left-sided endocarditis is highly prone to systemic embolization of septic microthrombi to the brain, spleen, kidneys, and limbs.
• Central nervous system complications include life-threatening ischemic and hemorrhagic strokes, subarachnoid hemorrhage, and the development of mycotic cerebral aneurysms.
• Embolic and immunological vascular phenomena include Janeway lesions (nontender, erythematous, macular micro-abscesses on the palms and soles) and splinter hemorrhages in the nail beds.
• Immunological complex deposition results in Osler nodes (tender, erythematous nodules over the finger pulps), Roth spots (retinal petechiae or microthrombi), and acute immune complex-mediated glomerulonephritis.

Diagnostic Investigations

Auscultation

• A new pathologic heart murmur, or a distinct change in the character of a pre-existing murmur, is a classic finding present in up to 100% of previously healthy children who develop endocarditis.
• The murmurs are typically regurgitant in nature, such as the pansystolic murmur of mitral regurgitation or the early diastolic decrescendo murmur of aortic regurgitation.
• If congestive heart failure ensues secondary to severe valvular insufficiency, a pathologic gallop rhythm (S3 or S4) and pulmonary crepitations may be appreciated.

Electrocardiogram (ECG)

• The ECG is routinely performed to evaluate for complications related to the infective process, specifically investigating for new conduction abnormalities.
• The extension of a perivalvular or myocardial abscess into the cardiac conduction system can manifest as new-onset prolonged PR intervals, atrioventricular (AV) blocks, or complete heart block.
• Ventricular ectopy and nonspecific ST-T wave changes may also be noted if there is an accompanying toxic myocarditis.

Chest Radiograph (CXR)

• The chest radiograph may demonstrate bilateral pulmonary infiltrates, multiple nodular lesions, or septic pulmonary infarcts, particularly in patients with right-sided endocarditis.
• Pleural effusions and significant cardiomegaly with perihilar pulmonary venous congestion may be present if the patient has developed congestive heart failure.

Echocardiography

• Two-dimensional echocardiography is the primary modality for detecting intracardiac manifestations, localizing the vegetation, evaluating its size and mobility, and assessing the degree of valvular dysfunction via color Doppler.
• Pathologic findings include an oscillating intracardiac mass (vegetation), newly acquired valvular regurgitation, valvular perforation, chordal rupture, perivalvular abscess, pseudo-aneurysm formation, intracardiac fistulae, and new partial dehiscence of a prosthetic valve.
• Transthoracic echocardiography (TTE) is highly sensitive in children under 10 years of age or weighing less than 60 kg due to optimal acoustic windows.
• Transesophageal echocardiography (TEE) is superior and highly indicated when evaluating prosthetic valves, assessing patients at high risk for aortic root abscesses, evaluating para-valvar disease, or when TTE acoustic windows are limited.
• A negative echocardiogram does not conclusively rule out the diagnosis of infective endocarditis.

Blood Cultures and Laboratory Studies

• Positive blood cultures are the absolute cornerstone of diagnosis; three to five separate blood collections should be obtained using strict aseptic techniques.
• Because bacteremia in endocarditis is continuous, blood cultures do not need to be timed with temperature spikes.
• In clinically stable patients, it is highly recommended to withhold empirical antibiotics until all necessary blood cultures have been drawn to maximize the diagnostic yield.
• Culture-negative endocarditis (CNE) occurs in 5% to 10% of cases, most frequently due to the prior administration of antibiotics.
• For CNE or suspected fastidious organisms, advanced molecular techniques such as polymerase chain reaction (PCR) amplification and metagenomic next-generation sequencing of bacterial 16S rDNA or fungal 18S rDNA from blood or surgically resected valve tissue are utilized.
• Supportive, nonspecific laboratory findings include a normocytic normochromic anemia, leukocytosis, thrombocytopenia, elevated acute phase reactants (C-reactive protein and erythrocyte sedimentation rate), hypergammaglobulinemia, hypocomplementemia, positive rheumatoid factor, and microscopic hematuria indicating glomerulonephritis.

Diagnostic Criteria (Modified Duke Criteria)

• The diagnosis of infective endocarditis is formalized using the Modified Duke Criteria, which categorizes patients into Definite, Possible, or Rejected cases based on pathological or clinical findings.
• A clinical diagnosis of Definite Infective Endocarditis requires the presence of 2 Major criteria; OR 1 Major and 3 Minor criteria; OR 5 Minor criteria.
• Possible Infective Endocarditis requires 1 Major and 1 Minor criterion; OR 3 Minor criteria.

Management

Medical Management

• The eradication of the bacteria requires prolonged courses of parenteral, bactericidal antimicrobial therapy, typically administered intravenously for 4 to 6 weeks, because the bacteria within the vegetation are metabolically inactive and protected by a dense fibrin-platelet matrix.
• Empirical therapy for acutely ill patients prior to culture results typically consists of Vancomycin combined with Gentamicin to broadly cover S. aureus, enterococci, and viridans streptococci.

Surgical Management

• Surgical intervention, involving the debridement of infected tissue and the repair or replacement of the affected cardiac valve, is frequently required to stabilize hemodynamics and achieve definitive source control.
• Heart Failure: Surgery is urgently indicated for severe acute aortic or mitral valve regurgitation, valvular obstruction, or intracardiac fistulae causing cardiogenic shock or intractable pulmonary edema.
• Uncontrolled Infection: Surgery is required for locally destructive expanding infections (perivalvular abscesses, mycotic aneurysms, pseudo-aneurysms), fungal endocarditis, multiresistant organisms, infections of pacing leads, or persistently positive blood cultures despite appropriate antimicrobial therapy.
• Prevention of Embolism: Surgery is indicated to prevent catastrophic systemic embolization in patients harboring highly mobile vegetations greater than 10 mm accompanied by severe valvular dysfunction, or vegetations exceeding 15 mm in size.

Prevention and Prophylaxis

• The maintenance of meticulous, routine daily oral hygiene and regular dental evaluations are heavily emphasized as the most critical interventions to prevent endocarditis, as daily activities like chewing and tooth brushing cause frequent, low-grade bacteremia that poses a greater cumulative risk than isolated invasive procedures.
• The administration of prophylactic antibiotics before dental procedures is strictly limited to patients with the highest risk of severe adverse outcomes from infective endocarditis.
• Conditions requiring prophylaxis include: patients with prosthetic mechanical or biological heart valves; patients with completely repaired congenital heart defects utilizing prosthetic material during the first 6 months post-procedure; patients with repaired congenital heart disease with residual hemodynamic defects adjacent to a prosthetic patch; patients with unrepaired complex cyanotic heart disease (including palliative shunts and conduits); cardiac transplant recipients with newly acquired valvulopathy; and patients with a previous history of infective endocarditis.
• For qualifying patients, prophylaxis is indicated exclusively before dental procedures that involve the manipulation of gingival tissue, the periapical region of the teeth, or the perforation of the oral mucosa.
• A single oral dose of Amoxicillin (50 mg/kg) is administered 30 to 60 minutes prior to the procedure.
• If the patient has a documented penicillin allergy, appropriate alternatives include oral Clindamycin, Azithromycin, or Clarithromycin.