What is the recommended treatment for infective endocarditis?

Treatment of Infective Endocarditis

The recommended treatment for infective endocarditis is pathogen-specific antibiotic therapy for 4-6 weeks, with specific regimens based on the causative organism, valve type (native vs. prosthetic), and antimicrobial susceptibility patterns. 1

Empirical Treatment Approach

When blood cultures are pending but treatment must be initiated:

• For community-acquired native valve or late prosthetic valve endocarditis (≥12 months post-surgery):

  • Ampicillin 12 g/day IV in 4-6 doses, PLUS
  • (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses, PLUS
  • Gentamicin 3 mg/kg/day IV or IM in 1 dose 1

• For early prosthetic valve endocarditis (<12 months post-surgery) or healthcare-associated endocarditis:

  • Vancomycin 30 mg/kg/day IV in 2 doses, PLUS
  • Gentamicin 3 mg/kg/day IV or IM in 1 dose, PLUS
  • Rifampin 900-1200 mg IV or orally in 2-3 divided doses 1

Pathogen-Specific Treatment

1. Staphylococcal Endocarditis

Native Valve Infections:

• Methicillin-susceptible S. aureus (MSSA):

  • (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses for 4-6 weeks 1
  • Addition of gentamicin for first 3-5 days is optional but increases risk of renal toxicity 1

• Methicillin-resistant S. aureus (MRSA):

  • Vancomycin 30-60 mg/kg/day IV in 2-3 doses for 4-6 weeks 1
  • Target trough vancomycin levels: 15-20 mg/L 1

Prosthetic Valve Infections:

• Methicillin-susceptible staphylococci:

  • (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses for ≥6 weeks, PLUS
  • Rifampin 900-1200 mg IV or orally in 2-3 divided doses for ≥6 weeks, PLUS
  • Gentamicin 3 mg/kg/day IV or IM in 1-2 doses for 2 weeks 1, 2

• Methicillin-resistant staphylococci:

  • Vancomycin 30 mg/kg/day IV in 2 doses for ≥6 weeks, PLUS
  • Rifampin 900-1200 mg IV or orally in 2-3 divided doses for ≥6 weeks, PLUS
  • Gentamicin 3 mg/kg/day IV or IM in 1-2 doses for 2 weeks 1, 2

2. Streptococcal Endocarditis

• Penicillin-susceptible streptococci:

  • Penicillin G or Amoxicillin for 4 weeks (native valve) or 6 weeks (prosthetic valve)
  • Alternative: Ceftriaxone for same duration 1

• Penicillin-resistant streptococci:

  • Penicillin G or Amoxicillin plus gentamicin for 2 weeks, then penicillin alone to complete 4-6 weeks 1
  • Alternative: Vancomycin for 4-6 weeks 1

3. Enterococcal Endocarditis

• Ampicillin-susceptible, gentamicin-susceptible:

  • Ampicillin 200 mg/kg/day IV in 4-6 doses for 4-6 weeks, PLUS
  • Gentamicin 3 mg/kg/day IV or IM in 1 dose for 2-6 weeks 1

• Ampicillin-resistant or high-level aminoglycoside resistance:

  • Vancomycin 30 mg/kg/day IV in 2 doses for 6 weeks 1

4. Blood Culture-Negative Endocarditis

• Consult with infectious disease specialist
• Empiric therapy based on most likely pathogens
• Consider special diagnostic tests for atypical organisms 1

5. Fungal Endocarditis

• Combined antifungal therapy plus surgical valve replacement
• High mortality rate (>50%) 1

Special Considerations

Monitoring During Treatment

• Gentamicin: Monitor renal function and serum levels weekly

  • Target trough levels <1 mg/L
  • Target peak levels 10-12 mg/L (1 hour after injection) 1

• Vancomycin: Monitor serum levels weekly

  • Target trough levels 15-20 mg/L
  • Target peak levels 30-45 mg/L (1 hour after infusion) 1

Surgical Intervention

• Patients with S. aureus endocarditis should be cared for in a facility with cardiothoracic surgery capabilities 1
• Consider early surgery for:
  • Heart failure due to valve dysfunction
  • Uncontrolled infection
  • Prevention of embolic events 1

Outpatient Parenteral Antibiotic Therapy (OPAT)

• May be considered after 2 weeks of inpatient treatment if:
  • Patient is clinically stable
  • No complications (heart failure, concerning echocardiographic features)
  • Reliable follow-up is available 1

Common Pitfalls and Caveats

1. Inadequate duration of therapy: Always complete the full course (4-6 weeks)

2. Inappropriate antibiotic selection: Base treatment on culture results and susceptibility testing

3. Insufficient monitoring: Regular clinical and laboratory monitoring is essential to detect complications early

4. Delayed surgical evaluation: Early surgical consultation is critical, especially for prosthetic valve endocarditis

5. Rifampin timing: When used in prosthetic valve infections, start rifampin 3-5 days after initiating other antibiotics to prevent resistance development 1, 2

6. Aminoglycoside toxicity: Monitor renal function closely, especially in elderly patients or those with pre-existing renal impairment

7. Failure to identify source: Persistent bacteremia may indicate an unidentified focus of infection requiring intervention