Infective endocarditis (IE), caused in over 80% of cases by streptococci and staphylococci, can also be attributed to other pathogens such as fungi, chlamydia, rickettsia, and viruses. The mortality rate of IE has significantly decreased in recent years due to advancements in antibiotics and surgical techniques. However, its incidence has not shown a notable decline because of factors such as changes in causative microorganisms, increased cardiac surgeries and catheter procedures, and the rising frequency of long-term intravenous catheterizations.
Etiology
Underlying Cardiac Abnormalities
Over 90% of IE patients have preexisting cardiac conditions, with congenital heart disease being the most common, accounting for approximately 80% of cases. These include ventricular septal defects, patent ductus arteriosus, aortic stenosis, and complex cyanotic congenital heart defects. Acquired heart diseases, such as rheumatic valvular disease or mitral valve prolapse syndrome, can also predispose to IE. Internal cardiac patches and prosthetic heart valves are additional risk factors that have become more prominent in recent years.
Pathogens
Almost all bacteria have the potential to cause IE. Alpha-hemolytic streptococci and Staphylococcus aureus are the most common pathogens. Cases caused by Staphylococcus epidermidis, enterococci, and gram-negative bacilli such as Klebsiella are on the rise. Rarely, IE can be caused by multiple pathogens, often linked to patients who have undergone prosthetic valve surgeries.
Triggering Factors
About one-third of pediatric patients have identifiable triggering factors in their medical history. Common triggers include dental procedures or tonsillectomy. In recent years, the prevalence of cardiac catheterization, interventional treatments, central venous catheterizations, prosthetic valve replacements, and open-heart surgeries has increased and become important contributors to the development of IE. Additional triggers include prolonged use of antibiotics, glucocorticoids, or immunosuppressants.
Pathology
In healthy individuals, certain colonizing bacteria commonly inhabit the oral cavity and upper respiratory tract but are usually non-pathogenic. In cases where immune defenses are compromised, especially during oral infections, tooth extractions, or tonsillectomies, these bacteria can enter the bloodstream. If the endocardium, particularly the heart valves, have pathological changes or congenital defects, the bacteria can adhere to and proliferate on the endocardial surface, leading to endocarditis. A significant pressure gradient across heart chambers or between large vessels can result in high-velocity blood flow, damaging the endocardium and exposing subendothelial collagen tissue, which promotes the accumulation of platelets and fibrin, forming sterile vegetations.
Affected sites are typically on the lower-pressure side of abnormal anatomical structures, such as the right edge of a ventricular septal defect, the septal leaflet of the tricuspid valve, the pulmonary valve, or the pulmonary artery in cases of patent ductus arteriosus. In aortic regurgitation, the lesions are on the left ventricle. The greater the pressure gradient and turbulence across stenotic valves or abnormal channels, the more likely thrombosis and vegetations are on the low-pressure side.
The primary pathological feature of IE is the presence of wart-like infectious vegetations attached to the surfaces of heart valves, endocardium, or the intima of large blood vessels. These vegetations are composed of platelets, white blood cells, red blood cells, fibrin, collagen fibers, and microorganisms. Valve vegetations can result in ulceration and perforation of the valve. Involvement of chordae tendineae and papillary muscles can lead to shortening or rupture of chordae. Extensions to the valve annuli and myocardium may cause myocardial abscesses, ventricular septal perforations, or aneurysms. Large or multiple vegetations can obstruct valve orifices or the pulmonary artery, leading to acute circulatory disturbances.
Detached thrombi from vegetations can be carried by high-velocity blood flow and disseminated throughout the circulatory system, causing embolism in various organs. Emboli originating from the right heart lead to pulmonary embolism, whereas those from the left heart result in arterial embolism, affecting the kidneys, brain, spleen, extremities, or mesenteric arteries. Microemboli may block capillaries and result in petechiae on the skin, such as Osler nodes. Renal embolism can lead to infarction, focal nephritis, or diffuse glomerulonephritis. Cerebral embolism can cause diffuse inflammation of the meninges, brain parenchyma, spinal cord, and cranial nerves, resulting in complications such as bleeding, edema, brain softening, abscess formation, or rupture of intracranial aneurysms. The latter can result in various forms of intracranial hemorrhage, including cerebral or subarachnoid hemorrhage.
Clinical Manifestations
The symptoms and severity of IE depend on the associated complications and infecting microorganisms.
Fever
Fever is the most common symptom, with body temperatures exceeding 38°C in the majority of cases. The fever may present with an irregular pattern or as low-grade fever. In some instances, body temperature remains normal.
Heart Failure and Cardiac Murmurs
Some patients may exhibit heart failure, or worsening of preexisting heart failure. Valvular damage with regurgitation may result in the appearance of new cardiac murmurs or changes in the nature and intensity of preexisting murmurs, although these changes may sometimes be subtle.
Vascular Manifestations
These include petechiae (commonly on the conjunctiva, oral mucosa, trunk, or extremities) and Janeway lesions (non-tender, erythematous macules on the palms and soles), though these findings are less frequent. Embolism of major vessels (e.g., pulmonary, cerebral, renal, mesenteric, or splenic arteries) is an important complication of IE and can result in ischemic or hemorrhagic symptoms in affected areas, such as chest pain, hemiplegia, hematuria, or abdominal pain.
Immunological Manifestations
Findings such as splinter hemorrhages (dark red, linear streaks under the nails), Osler nodes (tender, red subcutaneous nodules on the fingers or toes), and Roth spots (oval-shaped retinal hemorrhagic lesions with pale centers) are not unique to IE and are less frequently observed in clinical practice. Immune complex-mediated glomerulonephritis is noted in some patients and may manifest as hematuria or impaired renal function. In neonates, the clinical presentation is often atypical and difficult to differentiate from that of septicemia or heart failure caused by other conditions, with a high associated mortality rate.
Auxiliary Examinations
Blood Culture
A positive blood culture serves as an important criterion for confirming the diagnosis of IE. Patients with unexplained fever lasting more than one week, particularly those with preexisting heart conditions, often require repeated blood cultures to increase the likelihood of detecting the causative microorganism. When blood cultures are positive, antimicrobial susceptibility testing should be conducted. The most common pathogens identified are alpha-hemolytic streptococci and Staphylococcus aureus, accounting for more than 80% of positive blood cultures.
Echocardiography
Echocardiographic findings indicative of endocardial damage include the presence of vegetations, chordal rupture, valve perforation, partial dehiscence of intracardiac repair materials, intracardiac abscesses, and peri-prosthetic abscesses around artificial valves. In pediatric patients with IE, echocardiographic evidence of endocardial involvement is observed in approximately 85% of cases.
CT or MRI
Cranial CT or MRI should be pursued promptly in patients suspected of intracranial complications to assess the location and extent of the lesions.
Other Tests
Progressive anemia, typically normocytic anemia, may be noted in complete blood counts. Additional findings include elevated white blood cell counts, increased proportions of neutrophils, accelerated erythrocyte sedimentation rate (ESR), elevated C-reactive protein (CRP), increased serum globulin and immunoglobulin levels, and positive circulating immune complexes or rheumatoid factor. Urinalysis may show the presence of red blood cells, and proteinuria may occur during febrile episodes.
Diagnosis
Pathological Criteria
These include:
- Vegetations (including those associated with embolism) or cardiac infected tissue demonstrating microorganisms through culture or microscopic examination.
- Evidence of active endocarditis confirmed by pathological examination of vegetations or infected cardiac tissue.
Clinical Criteria
Major Criteria:
- Positive blood cultures: Isolation of the same common IE-associated microorganism (e.g., alpha-hemolytic streptococci, Staphylococcus aureus, coagulase-negative staphylococci, enterococci) from at least two blood cultures.
- Evidence of endocardial involvement (as documented by echocardiographic findings):
- Vegetations located on valves, valve apparatus, endocardium of the heart or great vessels, or prosthetic materials.
- Chordal rupture, valve perforation, or partial dehiscence of artificial valves or repair patches.
- Intracardiac abscess.
Minor Criteria:
- Predisposing factors: Underlying cardiac conditions, cardiac surgery, catheterization, transcatheter interventional treatments, presence of a central venous catheter, etc.
- Persistent fever (≥38°C) accompanied by anemia.
- Worsening of preexisting heart murmurs, new murmurs, or heart failure.
- Vascular phenomena: Major arterial embolism, infectious arterial aneurysm, petechiae, splenomegaly, intracranial hemorrhage, conjunctival hemorrhage, or Janeway lesions.
- Immunological phenomena: Glomerulonephritis, Osler nodes, Roth spots, or positive rheumatoid factor.
- Microbiological evidence: Positive blood cultures not meeting major criteria.
Diagnostic Criteria
A diagnosis of IE can be established when any of the following is met:
- Two major clinical criteria.
- One major criterion and three minor criteria.
- Evidence of endocardial involvement and two minor criteria.
- Five minor criteria.
- At least one pathological criterion.
IE can be excluded when:
- A clear alternative diagnosis explains the manifestations of endocarditis.
- Clinical symptoms resolve with ≤4 days of antibiotic therapy.
- No pathological evidence of IE is found during surgery or autopsy after ≤4 days of antibiotic treatment.
If IE is clinically suspected but diagnostic criteria are not fully met, treatment is still warranted. A definitive diagnosis or exclusion of IE should be based on further clinical observations and additional investigative findings.
Treatment
The general principles of treatment include aggressive infection control and supportive therapy. Multiple blood cultures and antimicrobial susceptibility testing must be performed before initiating antibiotic therapy to guide the selection of appropriate antibiotics and their dosage.
General Treatment
General treatment encompasses careful nursing care, ensuring adequate caloric intake, and, if necessary, administering small, repeated transfusions of fresh blood or plasma. Immunoglobulin infusion is also an option.
Antibiotic Therapy
The treatment principles for antibiotic use are early initiation, combination therapy, sufficient dosage, adequate treatment duration, and the selection of antibiotics based on susceptibility. Different antibiotics should be chosen based on the specific causative pathogen. Antibiotic therapy typically lasts for 4 to 8 weeks and continues until body temperature normalizes, embolic events resolve, peripheral blood counts and erythrocyte sedimentation rate (ESR) return to normal, and blood cultures become negative. Blood cultures need to be re-evaluated 8 weeks after discontinuation of antibiotics.
Surgical Treatment
Early surgical intervention for IE has achieved favorable outcomes in recent years. Surgical indications include:
- Moderate to severe heart failure caused by valvular dysfunction.
- Persistent high fever and enlarging vegetations despite more than one week of antibiotic therapy.
- Recurrent embolic events.
- Fungal infections.
- Perforation or damage to heart valves.
Prognosis and Prevention
With the appropriate use of antibiotics in recent years, the mortality rate of IE has significantly decreased. However, patients with severe residual valvular damage may require valve repair or replacement surgery. Children with congenital or rheumatic heart disease should maintain good oral hygiene to prevent gingivitis and dental caries, as well as reduce the risk of infections. When undergoing dental procedures, tonsillectomy, cardiac catheterization, or heart surgeries, prophylactic antibiotics can be administered 1 to 2 hours before the procedure and continued for 48 hours postoperatively.