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Infective Endocarditis (IE)

BASICS

  • Infection of valvular (primarily) and/or mural endocardium.
  • Systems affected: cardiovascular, endocrine/metabolic, hematologic, immunologic, pulmonary, renal, skin, neurologic.
  • Synonyms: bacterial endocarditis, subacute bacterial endocarditis (SBE), acute bacterial endocarditis (ABE).

EPIDEMIOLOGY

  • Male predominance (ratio 3:2 to 9:1).

  • 50% cases in U.S. in patients >60 years old.

  • Incidence ~15/100,000, rising.
  • Predominantly community-associated; ~1/3 health care-acquired in resource-rich countries.
  • Rising device-related infections due to implantable devices.
  • Most commonly affects mitral and aortic valves (high left-sided pressure/turbulence).

ETIOLOGY AND PATHOPHYSIOLOGY

  • Nonbacterial thrombus adheres to endocardial surface → seeded by bacteria from bloodstream or direct trauma.

Organisms by type:

  • Native valve acute: Staphylococcus aureus, Streptococcus groups A,B,C,G, S. pneumoniae, S. lugdunensis, Enterococcus spp., Haemophilus spp., Neisseria gonorrhoeae.
  • Native valve subacute: α-hemolytic streptococci, Streptococcus bovis, Enterococcus spp., S. aureus, S. epidermidis, HACEK group.
  • IV drug use (tricuspid): S. aureus, Enterococcus spp., Pseudomonas, Burkholderia, Candida.
  • Prosthetic valve early (<12 mo): S. aureus, S. epidermidis, gram-negative bacilli, Candida, Aspergillus.
  • Prosthetic valve late (>12 mo): α-hemolytic streptococci, S. aureus, Enterococcus spp., S. epidermidis, Candida, Aspergillus.
  • Culture-negative (~10%): Bartonella, Brucella, fungi, Coxiella burnetii, Chlamydia, HACEK.
  • Device-related: coagulase-negative staphylococci, S. aureus.

RISK FACTORS

  • Injection drug use, IV catheters, malignancies (colon cancer), poor dentition/infection, chronic dialysis, age >60, male sex, implantable devices.
  • Highest risk: previous IE, prosthetic valves, cardiac transplant with valvulopathy, prosthetic repair material, congenital heart disease (unrepaired cyanotic or residual shunts).

GENERAL PREVENTION

  • Good oral hygiene.
  • Antibiotic prophylaxis only for high-risk patients (30-60 minutes prior procedure; vancomycin 120 minutes prior).
  • Prophylaxis indicated for dental procedures involving gingival/periapical manipulation or oral mucosa perforation.
  • Prophylaxis regimens:
  • Oral/upper respiratory: Amoxicillin 2 g PO 30-60 min before, or ampicillin IV/IM; clindamycin no longer recommended.
  • GI/GU: cover Enterococcus if infection present.
  • Cardiac surgery/prosthetic placement: cefazolin or vancomycin perioperatively.
  • Skin/soft tissue: agents active against skin pathogens (cefazolin or vancomycin).

COMMONLY ASSOCIATED CONDITIONS

  • Most patients have preexisting conditions per risk factors.

DIAGNOSIS

Modified Duke Criteria

  • Definite IE: 2 major, or 1 major + 3 minor, or 5 minor criteria.
  • Possible IE: 1 major + 1 minor, or 3 minor criteria.
  • Rejected: alternative diagnosis, resolution ≤4 days on antibiotics, or insufficient criteria.

Major criteria

  • Positive blood cultures: typical IE microorganisms (2 separate cultures or persistently positive).
  • Single positive for Coxiella burnetii (phase-1 IgG >1:800).
  • Positive echocardiogram: vegetation, abscess, prosthetic valve dehiscence.
  • New valvular regurgitation.

Minor criteria

  • Predisposing heart condition or IV drug use.
  • Fever ≥38°C.
  • Vascular phenomena: emboli, septic infarcts, aneurysm, hemorrhages, Janeway lesions.
  • Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor.
  • Microbiologic evidence (not meeting major).

HISTORY

  • Fever, chills, cough, dyspnea, orthopnea.
  • Subacute IE: night sweats, weight loss, fatigue.
  • Review risk factors.
  • Symptoms of TIA, stroke, MI.

PHYSICAL EXAM

  • New or changing murmur.
  • Signs of heart failure.
  • Peripheral stigmata: splinter hemorrhages, Osler nodes, Roth spots, Janeway lesions, petechiae, splenomegaly, hematuria.
  • Neurologic deficits consistent with stroke.

DIFFERENTIAL DIAGNOSIS

  • Vasculitis, temporal arteritis, fever of unknown origin, infected central line, marantic endocarditis, connective tissue disease, abdominal infections, rheumatic fever, salmonellosis, brucellosis, Lyme disease, malignancy, tuberculosis, atrial myxoma, septic thrombophlebitis.

DIAGNOSTIC TESTS & INTERPRETATION

  • Blood cultures: 3 sets >2 hours apart before antibiotics; if acutely ill, 3 sets within 1 hour prior.
  • Labs: leukocytosis, anemia, decreased complement, positive RF, ESR, CRP, hematuria.
  • Serologies for culture-negative IE: Chlamydia, Q fever, Legionella, Bartonella.
  • Echocardiography: TTE or TEE preferred for vegetations, abscess, valve function.
  • Imaging: chest X-ray, CT chest/abdomen/pelvis for septic emboli or infarcts.
  • ECG: conduction abnormalities indicate myocardial involvement.

TREATMENT

GENERAL MEASURES

  • Targeted antibiotic therapy based on cultures.
  • Duration from first negative blood culture.

MEDICATION

Organism/Condition Regimen
Native valve empiric Ampicillin-sulbactam IV + gentamicin IV/IM; penicillin allergy: vancomycin + gentamicin + ciprofloxacin
Prosthetic valve (<12 months) Vancomycin + gentamicin + rifampin
Prosthetic valve (>12 months) Same as native valve regimen
Penicillin-susceptible viridans streptococci or S. bovis Penicillin G IV or ceftriaxone for 4 weeks (native valve), 6 weeks (prosthetic) ± gentamicin for 2 weeks (prosthetic)
Penicillin-resistant viridans streptococci or S. bovis Penicillin G IV + gentamicin for native valve; penicillin or ceftriaxone + gentamicin for prosthetic
Penicillin-susceptible Staphylococcus Native valve: oxacillin/nafcillin IV 6 weeks; oxacillin-resistant: vancomycin 6 weeks
Prosthetic valve: oxacillin/nafcillin + rifampin + gentamicin 6 weeks; resistant strains: vancomycin + rifampin + gentamicin
Penicillin-resistant Staphylococcus Vancomycin or daptomycin for 6 weeks (native valve); plus rifampin + gentamicin (prosthetic)
Penicillin-sensitive Enterococcus Ampicillin or penicillin G + gentamicin for 4-6 weeks
HACEK organisms Ceftriaxone or ampicillin-sulbactam or ciprofloxacin for 4 weeks

SURGERY/OTHER PROCEDURES

  • Required in ~50% cases.
  • Indications:
  • Heart failure due to valve disease.
  • Embolism prevention: large vegetations (>10 mm with emboli, >15 mm isolated).
  • Uncontrolled infection: persistent fever, resistant organisms, abscess/fistula.
  • Early prosthetic valve IE.

ONGOING CARE

FOLLOW-UP

  • Monitor ECG for conduction blocks, MI.
  • TTE at therapy conclusion.
  • Blood cultures every 48h until clearance.

PROGNOSIS

  • 1-year mortality ~30%.
  • Late complications worsen outcome: heart failure, reinfection, cerebral emboli.
  • 10-year survival 60-90%.

COMPLICATIONS

  • Cerebral (15-20%): stroke, neurologic events.
  • Emboli: arterial, abscesses (heart, lung, brain, meninges, bone, pericardium).
  • Immune/inflammatory: arthritis, myositis, glomerulonephritis.
  • Other: congestive heart failure, ruptured valve, aneurysms, arrhythmias.

REFERENCES

  1. McDonald EG, Aggrey G, Aslan AT, et al. Guidelines for diagnosis and management of infective endocarditis in adults: a WikiGuidelines Group consensus statement. JAMA Netw Open. 2023;6(7):e2326366.

ADDITIONAL READING

  • Cimmino G, Bottino R, Formisano T, et al. Current views on infective endocarditis: changing epidemiology, improving diagnostic tools and centering the patient for up-to-date management. Life (Basel). 2023;13(2):377.
  • Hussein H, Montesinos-Guevara C, Abouelkheir M, et al. Quality appraisal of antibiotic prophylaxis guidelines to prevent infective endocarditis following dental procedures: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2022;134(5):562-572.

CODES

  • ICD10 I33.0 Acute and subacute infective endocarditis
  • ICD10 I39 Endocarditis and heart valve disorders in diseases classified elsewhere
  • ICD10 A54.83 Gonococcal heart infection

CLINICAL PEARLS

  • Antibiotic prophylaxis recommended for patients with artificial valves, prior IE, CHD, cardiac transplants with valvulopathy.
  • TEE/TTE and blood cultures remain diagnostic mainstays.
  • Most common organisms: viridans streptococci and Staphylococcus species.
  • Most commonly involved valves: mitral, aortic, combined aortic/mitral, tricuspid, pulmonic.