Infective Endocarditis (IE)

Definition

• Robbins & Kumar Basic Pathology, p. 368

Classification

Epidemiology

• Annual incidence: ~3-14 cases per 100,000 persons/year in Western countries
• In developing countries: predominantly subacute IE from viridans streptococci on rheumatic heart disease valves
• In developed countries: predominantly S. aureus, often healthcare-associated or linked to injection drug use (IDU)
• S. aureus has become the most common cause in most high-income countries due to increasing medical interventions
• Prosthetic valve IE (PVE) accounts for 10-20% of all IE cases

Microbiology

Pathogenesis

1. Predisposing cardiac lesion - turbulent flow disrupts endothelium, creating a sterile platelet-fibrin thrombus (NBTE)
2. Bacteremia - organisms seed the thrombus (dental procedures, IV lines, skin infections, IDU, gut bacteria)
3. Vegetation formation - organisms proliferate within the thrombus, which expands with more fibrin and platelets
4. Local destruction - leaflet perforation, annular abscess, ring abscess (can extend to conduction system)
5. Embolization - friable vegetations shed septic emboli to brain, kidneys, spleen, lungs

• Mitral valve prolapse (now the leading pre-existing risk factor as rheumatic disease declines)
• Bicuspid aortic valve
• Calcific valvular stenosis
• Rheumatic heart disease
• Congenital heart disease (VSD)
• Prosthetic heart valves
• Intracardiac devices, pacemaker leads

Morphology of Vegetations

• RHD: Small beaded deposits along the line of closure
• IE: Large, friable, destructive vegetations with organisms; can invade underlying myocardium → ring abscess
• NBTE: Small, sterile, non-destructive vegetations on previously normal valves
• LSE (Libman-Sacks): Small, irregular lesions on both sides of the leaflet (SLE)

Clinical Features

Classic Signs

• Fever - the most consistent sign (may be absent in subacute IE in elderly)
• New or changing cardiac murmur - present in 90% of left-sided IE
• Splenomegaly - more common in subacute IE

Peripheral Stigmata (from emboli or immune complex deposition)

Janeway lesions = painless (embolic); Osler nodes = pAinful (immune)

Complications

• Local: Valvular destruction, perivalvular abscess, intracardiac fistula, heart block (from conduction system involvement), acute heart failure
• Embolic: Stroke (brain), renal/splenic infarcts, septic pulmonary emboli (right-sided IE), mycotic aneurysms
• Immune: Glomerulonephritis (immune complex-mediated), rheumatoid factor, arthralgias

Diagnosis: Modified Duke Criteria

DEFINITE IE

• 2 major criteria, OR
• 1 major + 3 minor criteria, OR
• 5 minor criteria

POSSIBLE IE

• 1 major + 1 minor, OR 3 minor criteria

REJECTED IE

• Firm alternate diagnosis, or resolution with antibiotics ≤4 days

Major Criteria

• Two separate blood cultures with typical IE organisms (S. viridans, S. gallolyticus, S. aureus, HACEK, Enterococcus without primary focus)
• Persistently positive blood cultures: ≥2 cultures drawn >12 hours apart, OR all of 3 or majority of 4 cultures drawn ≥1 hour apart
• Single positive culture for Coxiella burnetii (Q fever) or antiphase 1 IgG titer ≥1:800
• Positive PCR from blood for C. burnetii, Bartonella, or T. whipplei

• Vegetation, valvular perforation/aneurysm, abscess, pseudoaneurysm, intracardiac fistula
• New valvular regurgitation
• New abnormal activity on 18F-FDG PET/CT (useful especially in PVE)

Minor Criteria

1. Predisposing heart condition or IDU
2. Fever ≥38°C
3. Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions
4. Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor
5. Positive blood culture not meeting major criteria (or serological evidence of active infection with organism consistent with IE)

Investigations

Treatment

Empirical Therapy (before cultures)

• Native valve suspected: Vancomycin 15 mg/kg IV q12h (covers MRSA and streptococci)
• S. aureus confirmed: If MSSA - switch to oxacillin 2g IV q4h (superior to vancomycin for MSSA)

Specific Antibiotic Regimens

Infectious diseases consultation is strongly recommended to guide antimicrobial selection and duration.

Surgical Indications (AHA Guidelines)

Native Valve IE - Class I (Early Surgery Required)

1. Valve dysfunction causing symptoms of heart failure
2. IE caused by fungal or highly resistant organisms (e.g., VRE, MDR gram-negatives)
3. IE complicated by heart block, annular/aortic abscess, or destructive penetrating lesions
4. Persistent bacteremia or fever >5-7 days despite appropriate antibiotics

Native Valve IE - Class IIa (Early Surgery Reasonable)

1. Recurrent emboli + persistent/enlarging vegetations despite antibiotics
2. Severe valve regurgitation + mobile vegetations >10 mm

Right-Sided IE

• Surgery for heart failure, recurrent emboli, or resistant organisms
• Valve repair preferred over replacement when feasible
• Avoid surgery if possible in active IDU patients

Post-Stroke

• Surgery may proceed without delay if intracranial hemorrhage excluded and neurologic damage not severe
• Delay at least 4 weeks if major ischemic stroke or intracranial hemorrhage

Prophylaxis (AHA 2021 Update)

• Prosthetic cardiac valves (including transcatheter-implanted)
• History of IE
• Congenital heart disease (unrepaired cyanotic CHD; repaired CHD with residual defects near prosthetic material; within 6 months of repair)
• Cardiac transplant recipients with valvulopathy
• Ventricular assist devices and implantable hearts (added in 2021)

• Amoxicillin 2g PO 30-60 min before procedure (preferred)
• Clindamycin removed from 2021 guidelines due to C. difficile risk
• Doxycycline added as alternative in true penicillin-allergic patients
• Allergy screening: 90% of patients with reported penicillin allergy have negative skin testing - so amoxicillin can often be used

Prognosis

• Untreated IE is uniformly fatal
• With appropriate antibiotics ± surgery, in-hospital mortality remains 15-30%
• Adverse prognostic factors: S. aureus, heart failure, large vegetations, perivalvular extension, embolic stroke, renal failure, prosthetic valve involvement
• Multidisciplinary "endocarditis team" approach (infectious disease + cardiology + cardiac surgery) has been shown to improve outcomes