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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Suspect IE in any patient with fever + new murmur, especially with risk factors (IVDU, prosthetic valve, structural heart disease)
- Diagnosis: Modified Duke criteria (2 major, or 1 major + 3 minor, or 5 minor = definite IE)
- Blood cultures (3 sets from separate sites before antibiotics) + echocardiogram (TTE first, TEE if TTE negative but suspicion high or prosthetic valve)
- Most common organism overall: S. aureus (especially IVDU and acute native valve IE). Viridans streptococci for subacute native valve
- Empiric IV antibiotics for 4-6 weeks; surgery indicated for HF, uncontrolled infection, large vegetations, or embolic events
Overview
Infective endocarditis is an infection of the endocardial surface of the heart, most commonly affecting the heart valves. It occurs when bacteremia leads to colonization of damaged or abnormal endocardium, forming infected vegetations composed of platelets, fibrin, and microorganisms. IE is classified as acute (fulminant, days to weeks, typically S. aureus) or subacute (indolent, weeks to months, typically viridans streptococci). In the US, S. aureus has surpassed streptococci as the most common cause, particularly due to healthcare-associated infections and IV drug use.
Epidemiology
Incidence ~15 per 100,000 person-years in the US. Increasingly common due to more prosthetic valves, cardiac devices, hemodialysis, and the opioid epidemic (IVDU). Risk factors: IVDU (most common for right-sided IE), prosthetic heart valve, prior IE, structural heart disease (MR, AR, AS, bicuspid valve, MVP with regurgitation), intracardiac devices, poor dentition, hemodialysis. IVDU-associated IE typically affects the tricuspid valve. In-hospital mortality is ~15-25%.
Clinical Features
Symptoms
Fever (most common symptom, ~90%) with constitutional symptoms (malaise, night sweats, weight loss, myalgias)
New or changing heart murmur (~85%)
Embolic phenomena: stroke, splenic infarct, renal infarct, pulmonary emboli (right-sided IE)
Back pain (vertebral osteomyelitis or epidural abscess from hematogenous seeding)
Acute-onset HF (valvular destruction — especially acute AR)
Signs
Janeway lesions: painless erythematous macules on palms/soles (septic emboli)
Osler nodes: painful violaceous nodules on fingers/toes (immune complex deposition)
Splinter hemorrhages: linear red-brown lines under fingernails
Roth spots: retinal hemorrhages with pale centers (fundoscopy)
Splenomegaly (~30%)
Petechiae: conjunctival, oral mucosa, trunk
New regurgitant murmur (flail leaflet, perforation, or abscess)
Investigations
First-line
Blood cultures (3 sets)3 sets from separate venipuncture sites, ideally 30-60 min apart, BEFORE starting antibiotics. Culture-negative IE (~10%) seen with prior antibiotics, HACEK organisms, Coxiella, Bartonella, or fungi — consider serologies
Transthoracic echocardiogram (TTE)First-line imaging. Sensitivity ~70% for native valve IE. Look for vegetations, abscess, regurgitation, perforation
Basic labsCBC (anemia of chronic disease, leukocytosis), BMP, ESR/CRP (elevated), urinalysis (microscopic hematuria, RBC casts = immune complex GN), blood smear
Second-line
Transesophageal echo (TEE)Sensitivity ~95%. Indicated if: TTE negative but clinical suspicion high, prosthetic valve (TTE sensitivity drops to ~50%), suspected abscess or complications, or S. aureus bacteremia
Modified Duke criteriaMajor: 2 positive blood cultures with typical organism + endocardial involvement on echo. Minor: predisposing condition, fever >38C, vascular phenomena (Janeway, emboli), immunologic phenomena (Osler, Roth, GN), positive cultures not meeting major
Specialist
CT/MRI brainIf neurological symptoms — stroke (ischemic from septic emboli or hemorrhagic from mycotic aneurysm)
CT chest/abdomenSeptic pulmonary emboli (right-sided IE — multiple peripheral nodular infiltrates), splenic abscess/infarction
Cardiac CT or PET/CTProsthetic valve IE or cardiac device infection — can identify perivalvular abscess and extracardiac complications
1
Empiric antibiotics (before culture results)
- Native valve: vancomycin (MRSA coverage) + ceftriaxone (strep/HACEK coverage)
- Prosthetic valve: vancomycin + gentamicin + rifampin
- IVDU with suspected right-sided IE: vancomycin (S. aureus coverage is critical)
- Adjust to targeted therapy when culture and sensitivity results available
2
Definitive antibiotic therapy
- Viridans streptococci (MIC <=0.12): IV penicillin G or ceftriaxone x 4 weeks (can do 2-week course with gentamicin if native valve, uncomplicated)
- MSSA native valve: nafcillin or oxacillin x 6 weeks
- MRSA: vancomycin x 6 weeks (or daptomycin as alternative)
- HACEK organisms: ceftriaxone x 4 weeks
- Prosthetic valve IE: longer courses (>=6 weeks), often with combination therapy (e.g., vancomycin + gentamicin + rifampin for staph PVE)
- Enterococcus: ampicillin + gentamicin (synergistic) or ampicillin + ceftriaxone x 6 weeks
3
Surgical indications
- Heart failure from valvular dysfunction (most common surgical indication)
- Uncontrolled infection: persistent bacteremia >5-7 days despite appropriate antibiotics, perivalvular abscess, fistula
- Prevention of embolism: large vegetations (>10 mm) with embolic events, or very large vegetations (>15 mm) even without emboli
- Prosthetic valve IE caused by S. aureus or fungi (aggressive organisms with poor medical cure)
- Fungal endocarditis (medical cure rare — surgery + long-term antifungal)
4
Prophylaxis (AHA 2021)
- Only for highest-risk patients: prosthetic valve, prior IE, certain congenital heart disease (unrepaired cyanotic, repaired with residual defects, within 6 months of repair), cardiac transplant with valvulopathy
- Only for dental procedures involving gingival manipulation or periapical region
- Amoxicillin 2g PO 30-60 min before procedure (clindamycin if penicillin allergy)
- NOT indicated for native valvular disease (AS, MR, MVP) alone
Complications
- Heart failure: From acute valvular regurgitation (most common cause of death)
- Embolic stroke: ~20-40% of left-sided IE; can be first presentation
- Mycotic aneurysm: Septic emboli to arterial vasa vasorum — can rupture causing hemorrhagic stroke or other hemorrhage
- Perivalvular abscess: Most common with aortic valve IE, suggests surgical need
- Septic pulmonary emboli: Right-sided IE — multiple bilateral nodular infiltrates, may cavitate
- Immune complex GN: Microscopic hematuria, RBC casts, low complement
- Splenic abscess/infarction: May require splenectomy if abscess
USMLE Step 2 CK Exam Tips
- 1Fever + new murmur = endocarditis until proven otherwise. Get 3 sets of blood cultures BEFORE antibiotics
- 2S. aureus = most common organism overall and in acute IE/IVDU. Viridans strep = subacute native valve
- 3IVDU endocarditis = tricuspid valve (right-sided). Findings: septic pulmonary emboli (bilateral nodular infiltrates on CXR), NO peripheral embolic signs
- 4Janeway lesions are PAINless (septic emboli). Osler nodes are PAINful (immune complex). Mnemonic: FROM Jane's PAINLESS trip, Osler was in PAIN
- 5TEE is indicated if TTE negative but clinical suspicion high, prosthetic valve, or S. aureus bacteremia
- 6S. aureus bacteremia: ALWAYS get TTE (or TEE) even without murmur — ~25% have IE
- 7Endocarditis prophylaxis: only for highest-risk patients before dental procedures. NOT for native valve disease
- 8Culture-negative IE + exposure to cats = Bartonella. Homeless/lice = Bartonella. Q fever endemic area = Coxiella
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