Infective Endocarditis

PEDIATRIC INFECTIVE ENDOCARDITIS

DR MANSOUR ALQURASHI

Infective Endocarditis (IE) Definition

• IE is an infection of the endocardium and/or heart valves that involves thrombus formation (vegetation), which may damage the endocardial tissue and/or valves.
• IE can involve native endocardium/endothelium or prosthetic material.
• Incidence: Rates of IE <5 per 100,000 individuals per year. Rates are higher among infants <1 year old compared with older children and adolescents.

Risk Factors Z

• Congenital heart disease (CHD):
  • Complex cyanotic CHD, especially in those who have had surgical intervention.
• Central venous catheters (CVC):
  • Critically ill and premature infants and children with cancer or connective tissue disorders.
• Artificial heart valves or prosthetic materials.
• Rheumatic heart disease:
  • Severe valvular damage.
• Other risk factors:
  • Injection drug use.

Microbiology

• Common pathogens:
  • Staphylococcus aureus. Z most common
  • Alpha hemolytic streptococci (Viridans streptococci). Z community
  • Coagulase-negative staphylococci (e.g., Staphylococcus epidermidis).
  • Gram-negative bacilli.
• Fungi:
  • Candida.
  • Risk factors: Indwelling catheters and high glucose in parenteral nutrition (especially in preterm infants).
• Other pathogens:
  • HACEK organisms: Small, fastidious gram-negative bacilli common in neonates and immunocompromised children.
  • Enterococci, Brucella, Anaerobes.
  • Coxiella burnetii (Q fever), Rickettsiae, typhus, Chlamydia.

Clinical Manifestations

Acute IE

• A rapidly progressive & fulminant disease, characterized by high fever and severe illness.
• Common in IE due to S. aureus or Streptococcus pneumoniae, which cause rapid destruction of heart valve, abscess formation, embolic phenomena, and shock.
• Fungal IE can present as an acute fulminant infection.

Subacute IE

• More common than acute IE.
• Characterized by a prolonged course of low-grade fever and nonspecific complaints including fatigue, arthralgias, myalgias, chills, night sweats, weight loss, and exercise intolerance.
• The presence of a cluster of these symptoms in a patient at risk for IE (i.e., CHD or indwelling CVC) should raise the possibility of IE as a potential diagnosis.
• Less virulent pathogens (e.g., viridans group streptococci, coagulase-negative staphylococci) typically have a subacute presentation.
• Risk of immunologic sequelae, such as immune-mediated glomerulonephritis.

Clinical Findings by Age Group

Neonates

• Presentation of IE may be indistinguishable from bacterial sepsis.
• Common manifestations: Feeding intolerance, tachycardia, respiratory distress, hypotension, and a new or changing murmur. Fever may be absent.
• Neonates with right-sided IE in association with CVC characteristically have little clinical evidence of disease other than persistently positive blood cultures in the setting of appropriate antibiotic treatment.

Older Infants and Children

• Septicemia signs: Fever, vasodilation, and tachycardia.
• Subacute symptoms: Malaise, headache, myalgias, and arthralgias.
• Signs of valvulitis:
  • A new or changing murmur.
  • Signs of acute heart failure (e.g., dyspnea, tachypnea, rales) or poor systemic perfusion due to perforation of a valve, chordal rupture, or poor ventricular function.
  • Worsening cyanosis in children with underlying cyanotic CHD if IE involves either a systemic-pulmonary shunt or conduit. This is because the infection may obstruct blood flow across the shunt or conduit.
• Immune-mediated complications: Glomerulonephritis (subacute IE).
• Embolic complications:
  • Septic emboli are common, resulting in extracardiac infection (e.g., osteomyelitis, pneumonia, lung abscess).
  • Emboli can cause infarction to major vessels and organs:
    • Brain: May result in seizures, headache, strokes.
    • Other sites: Kidneys, lungs, GIT, and eyes.
  • Splenomegaly: 25–60%.
• Relatively uncommon manifestations (highly suggestive of IE):
  • Janeway lesions, Osler nodes, and Roth spots.

Specific Physical Signs

Janeway Lesions Nontender hemorrhagic macules or papules located on palms, soles, and thenar and hypothenar eminences.

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Osler Nodes Tender, painful, purple-pink nodules 1 to 1.5 mm on the distal fingers and toes, hypothenar, and thenar muscle. Caused by deposition of immune complexes.

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Conjunctival Petechiae

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Splinter Hemorrhages Small linear hemorrhages under the fingernails.

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Roth Spots Retinal hemorrhages that have white/pale centers.

Investigations

Nonspecific Investigations

• Anemia: Hemolytic or anemia of chronic disease (common feature of IE).
• Leukocytosis.
• Thrombocytopenia: Unusual.
• Rheumatoid Factor: Positive in 50% (resolves after treatment).
• Inflammatory Markers: Elevated ESR, CRP, procalcitonin.
• Urinalysis:
  • Hematuria, proteinuria, and RBC casts (suggestive of glomerulonephritis, a minor diagnostic criterion).
  • Pyuria (metastatic infection).
• ECG: Prolongation of the PR interval or frank heart block can occur with periannular extension.
• Chest Radiograph:
  • Nonspecific findings: Cardiomegaly, pulmonary edema, pleural effusions.
  • Focal pulmonary infiltrates (in patients with pulmonary septic emboli).
  • Peripheral nodular densities (metastatic lesions).

Specific Investigations

The diagnosis of IE is based upon history, physical examination, blood cultures, laboratory tests, and echocardiography.

Blood Cultures

• Cornerstone of microbiological diagnosis (95%).
• Procedure: Minimum of three blood cultures obtained over a time period of a few hours to two days, obtained from separate venipunctures.
• Critically Ill Children: Three separate venipunctures should be performed as quickly as possible (ideally within <30 minutes) and empiric antibiotic therapy started promptly.
• Considerations: Long incubation; check for HACEK organisms.

Serology/PCR

• PCR, IFA for detection of IgG and IgM antibodies.

Echocardiography

• Indication: An echocardiogram for all patients with suspected IE.
• Findings: Vegetations, myocardial abscess, valve competence.
• TTE (Transthoracic): Less sensitive for vegetations than TEE; used for adolescents or overweight children.
• TEE (Transesophageal): More sensitive.
• Other Imaging: Cardiac CT, FDG PET/CT and CMR imaging useful in select clinical situations.

Echocardiography Images

Mitral Valve Vegetation

Diagnosis: Duke Criteria Z - SMLE

Major Criteria

1. Positive blood culture: Z
   • 2 positive cultures for a typical pathogen.
   • OR 3 positive cultures for a non-typical pathogen.
2. Evidence of endocardial involvement:
   • Positive echocardiogram (vegetation or intra-cardiac abscess).
   • Evidence of endocardial involvement during surgery.

Minor Criteria

1. Fever.
2. Presence of predisposing heart disease.
3. Positive blood culture (but not for a typical pathogen and less than 3).
4. Echo finding (but not meeting major criterion).
5. New evidence of valve regurgitation (i.e., new coming murmur).
6. Immune phenomena: Osler node, Roth spot, or glomerulonephritis.
7. Vascular phenomena: Janeway lesion, arterial emboli, or intracranial hemorrhage.

Diagnostic Requirements

• 2 Major criteria.
• OR 1 Major criteria & 3 Minor criteria.
• OR 5 Minor criteria.

Treatment

• Goal: Complete eradication of the causing organism.
• Regimen: Prolonged, Parenteral, and Bactericidal antibiotic regimen guided by antibiotic sensitivity studies.

Empiric Therapy

• Indications: For patients with severe manifestations of acute IE, empiric treatment should be started as soon as diagnosis is suspected.
• Stable Patients: In children who are clinically stable, antibiotic therapy can be withheld for at least 48 hours until the results of blood cultures are available.
• Protocol: Empiric therapy should be administered after at least two (preferably three) sets of blood cultures have been obtained from separate venipunctures, ideally spaced over 30 to 60 minutes.
• Coverage: Staphylococci (methicillin-susceptible and methicillin-resistant), streptococci, enterococci, and gram-negative bacilli.

Regimens:

• Suspected Native Valve Endocarditis:
  • Vancomycin and Ceftriaxone.
• Suspected Prosthetic Valve Endocarditis:
  • Vancomycin (activity against enterococci and methicillin-resistant staphylococci).
  • PLUS either Cefepime or Piperacillin-tazobactam (activity against aerobic gram-negative organisms including Pseudomonas).

Surgical Indications in Endocarditis

• Hemodynamically unstable: a. New or worsening heart failure. b. Valvular dysfunction.
• Uncontrolled infection: a. Remaining positive blood cultures. b. Fungal endocarditis. c. Perivalvular or myocardial abscess.
• Embolic manifestations.

Prognosis and Complications

Risk Factors for Complications:

• Prosthetic cardiac valves.
• Left-sided involvement.
• S. aureus or fungal IE.
• Previous IE.
• Prolonged symptoms (≥3 months).
• Cyanotic congenital heart disease.
• Systemic-to-pulmonary shunts.
• Poor clinical response to antimicrobial therapy.

Statistics:

• Complications occur in 50-60% of cases.
• Mortality at 8%.

Complications of IE

Cardiac Complications:

• Heart failure: Caused by perforation of the valve, rupture of an infected chordae, or perivalvar leaks or dehiscence in patients with prosthetic valve.
• Extension of infection beyond the endothelium:
  • May cause perivalvular abscess (leading to an arrhythmia or atrioventricular heart block), myocardial abscesses, toxic myocarditis, acquired VSD.
• Obstruction: Extension of infection into a prosthetic shunt or conduits may occlude the graft. These infections require surgical intervention because they rarely respond to medical management.
• Acute myocardial infarction.

Metastatic Infection:

• Infection at other sites can occur from septic emboli resulting in osteomyelitis, pneumonia, or distal abscesses in the kidneys, spleen, brain, or soft tissues.

Neurological & Vascular Complications:

• Mycotic aneurysms: Can occur in any systemic artery and result from septic embolization or, occasionally, from contiguous spread of infection. This complication is an indication for surgery.
• Stroke: Occurs in 5 to 15 percent of pediatric IE cases, chiefly in the setting of left-sided IE.
• Other embolic events:
  • Pulmonary embolism (typically occurs in the setting of right-sided IE).
  • Ischemia of the extremities.
  • Splenic infarction.
  • Visual impairment (due to embolism or due to endophthalmitis as a result of bacteremic seeding).

Renal Complications:

• Acute kidney injury (AKI): Occurs in approximately 10 percent of pediatric patients with IE.
  • Causes: Renal infarction, glomerulonephritis (immune-mediated secondary process), and drug-induced acute interstitial nephritis.

Prevention & Prophylaxis Z

High-Risk Cardiac Conditions Requiring Prophylaxis

(Conditions with the Highest Risk of Adverse Outcome From Endocarditis or Which Prophylaxis With Dental Procedures Is Reasonable)

• Prosthetic cardiac valve or prosthetic material used for cardiac valve repair.
• Previous infective endocarditis.
• Congenital heart disease (CHD):
  • Unrepaired cyanotic CHD, including palliative shunts and conduits.
  • Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 mo after the procedure (endothelialization).
  • Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization).
• Cardiac transplantation recipients who develop cardiac valvulopathy.

Procedures Requiring Antimicrobial Endocarditis Prophylaxis

(In High-Risk Patients)

Category	Procedures
Oral-dental*	• Dental extraction • Dental implant placement or reimplantation of avulsed teeth • Periodontal procedures, including surgery, scaling, root planing, and probing • Prophylactic cleaning of teeth or implants when bleeding is anticipated • Root canal instrumentation or surgery beyond the apex
Respiratory tract	• Bronchoscopy if mucosa is to be incised • Procedures done during an established infection • Tonsillectomy, adenoidectomy, or both
*For patients without active infection.

Procedures NOT Requiring Prophylaxis

• TEE, esophagogastroduodenoscopy, colonoscopy, or cystoscopy, in the absence of active infection.
• GU or GI tract procedures do not require preprocedure antibiotics.
• Tattooing and body piercing.
• Implantable cardiovascular devices.

Recommended Prophylaxis Regimens

(During Oral-Dental or Respiratory Tract Procedures for patients without active infection)

Route	Drug	Adult Dosage	Children Dosage
Oral (Given 1 h before procedure)	Amoxicillin	2 g	50 mg/kg
	Allergic to Penicillin:
	Clindamycin	600 mg	20 mg/kg
	OR Cephalexin / Cefadroxil	2 g	50 mg/kg
	OR Azithromycin / Clarithromycin	500 mg	15 mg/kg
Parenteral (Given 30 min before procedure)	Ampicillin (IM or IV)	2 g	50 mg/kg
	OR Cefazolin (IM or IV)	1 g	25 mg/kg
	Allergic to Penicillin:
	Clindamycin (IV)	600 mg	20 mg/kg

Adapted from Wilson W, Taubert KS, Gewitz M, et al: Prevention of infective endocarditis. Circulation 116(15):1736–1754, 2007.