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Infective Endocarditis: Definition and Laboratory Sample Collection
Definition
Infective endocarditis (IE) is a microbial infection of the endovascular surfaces of the heart - most commonly the heart valves - leading to the formation of friable, bulky vegetations composed of fibrin, inflammatory cells, thrombotic debris, and microorganisms, often associated with destruction of the underlying cardiac tissue. The aorta, aneurysmal sacs, other blood vessels, and prosthetic devices may also be infected.
Technically, infections of cardiac shunts or those related to coarctation of the aorta are also classified together with IE due to similar clinical manifestations, microbiology, and treatment.
- Robbins & Kumar Basic Pathology, p. 368
- Tietz Textbook of Laboratory Medicine, 7th Ed., p. 3154
Classification: Acute vs. Subacute
| Feature | Acute IE | Subacute IE |
|---|
| Onset | Rapidly progressive | Insidious |
| Virulence of organism | High (e.g., S. aureus) | Low (e.g., viridans streptococci) |
| Valves affected | Normal or abnormal | Usually pre-damaged |
| Course without treatment | Rapidly fatal | Weeks to months |
| Morbidity/mortality | High even with treatment | Most recover with antibiotics |
Etiology
The three most common causes worldwide are staphylococci, streptococci, and enterococci:
- S. aureus - most common overall (especially healthcare-associated and IV drug users); 31% of cases
- Viridans group streptococci - most common in community-acquired IE on damaged valves; 17% of cases
- Enterococci - 10% of cases
- HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) - fastidious gram-negative oral commensals
- Candida spp. - most common fungal cause
- Culture-negative IE - approximately 10% of cases, often due to prior antibiotics or fastidious organisms
Morphology and Clinical Features
- Vegetations are found most commonly on the aortic and mitral valves (tricuspid valve is common in IV drug users)
- Vegetations are friable, potentially destructive, and may erode into the myocardium (ring abscess)
- Shedding of emboli leads to septic infarcts and mycotic aneurysms
Clinical signs:
- Fever (most consistent sign)
- New or changing cardiac murmur (90% of left-sided lesions)
- Peripheral manifestations: splinter hemorrhages, Janeway lesions (painless palmar/plantar macules), Osler nodes (painful fingertip nodules), Roth spots (retinal hemorrhages)
- Complications: glomerulonephritis, embolic stroke, septic arthritis, splenomegaly
Laboratory Diagnosis: Sample Collection
1. Blood Cultures (Primary and Most Important Test)
Blood culture is the single most important laboratory procedure for diagnosing IE. Because IE produces continuous bacteremia (as opposed to the transient bacteremia of dental procedures), the probability of isolating the organism from any single culture is high.
Collection procedure (from Jawetz Microbiology):
- Use strict aseptic technique; wear gloves
- Apply tourniquet and locate a vein by touch; release tourniquet during skin preparation
- Cleanse the skin vigorously with 70-95% isopropyl alcohol, then apply 2% tincture of iodine or 2% chlorhexidine in concentric circles from the venipuncture site outward; allow to dry for at least 30 seconds; do not touch the prepared site
- Reapply tourniquet, perform venipuncture, and withdraw approximately 20 mL of blood (adults)
- Inoculate blood into both aerobic and anaerobic blood culture bottles (half in each)
- Label properly and transport promptly to the laboratory
Number and timing of draws:
- For acute IE / Gram-negative sepsis with shock: a minimum of 2 blood cultures from different anatomic sites should be drawn urgently before starting antibiotics
- For subacute IE: at least 3 blood specimens over 24 hours - three cultures detect the infecting organism in >95% of bacteremic patients
- Per Goldman-Cecil: two sets (each 20-30 mL) from separate venipuncture sites is the standard; no need to space draws over time if urgent antibiotic therapy is needed
- Single-draw blood cultures are discouraged
- A contamination rate up to 3% is acceptable; to minimize contamination, a dedicated phlebotomy team is ideal
- Blood should be drawn before administration of antibiotics whenever possible
Distinguishing true positives from contamination:
- Growth of the same organism in repeated cultures from different sites = true bacteremia
- Growth of normal skin flora (coagulase-negative staphylococci, diphtheroids) in only one of several bottles = likely contamination
- Growth of viridans streptococci or enterococci in a patient suspected of IE = highly significant
2. Echocardiography (Non-laboratory but diagnostic)
Echocardiography (TTE/TEE) is an essential diagnostic tool and is a major criterion in the modified Duke criteria.
3. Serology
- If blood cultures are negative, Bartonella serology and Q fever (Coxiella burnetii) serology should be obtained
- Serologic evidence of infection is also a minor Duke criterion
4. Molecular Diagnostics / Histopathology (for Culture-Negative Cases)
Applied to resected valves when the microbiologic diagnosis has not been established by other means:
- 16S ribosomal RNA gene PCR / sequencing
- Tropheryma whipplei nucleic acid amplification testing (Whipple disease endocarditis)
- Histopathology and special stains on valve tissue
5. Special/Supplementary Cultures
- Mycobacteria and dimorphic fungi require specialized blood culture media and longer incubation times
- HACEK organisms are reliably isolated within 5 days using modern automated systems
6. Modified Duke Criteria (Diagnostic Framework)
| Major Criteria | Minor Criteria |
|---|
| ≥2 positive blood cultures with IE-typical organisms | Predisposing cardiac condition or IV drug use |
| Echographic evidence of endocarditis (vegetation, abscess, new prosthetic valve regurgitation) | Fever >38°C |
| Evidence of embolic phenomena |
| Immunologic phenomena (Osler nodes, Roth spots, glomerulonephritis) |
| Positive blood culture not meeting major criteria |
Sources:
- Robbins & Kumar Basic Pathology, pp. 367-369
- Tietz Textbook of Laboratory Medicine, 7th Ed., pp. 3154-3156
- Jawetz, Melnick & Adelberg's Medical Microbiology, 28th Ed., pp. 776-777
- Goldman-Cecil Medicine, Blood Cultures section
- Henry's Clinical Diagnosis and Management by Laboratory Methods, Specimen Draws section