What is the treatment for infective endocarditis?

Treatment of Infective Endocarditis

The treatment of infective endocarditis requires prompt initiation of appropriate bactericidal antibiotics for 4-6 weeks, combined with surgical intervention in approximately 50% of cases, and should be managed by a multidisciplinary "Endocarditis Team" whenever possible. 1

Initial Diagnostic Approach

• Obtain three sets of blood cultures at 30-minute intervals before initiating antibiotics to maximize pathogen identification 1
• Start empiric therapy promptly after blood cultures are drawn to prevent further valve destruction 2
• Consider blood culture-negative infective endocarditis (BCNIE) when initial cultures remain negative 3, 1

Empirical Antimicrobial Therapy

• Selection depends on several key factors:

  • Previous antibiotic exposure 1
  • Native valve versus prosthetic valve involvement 1
  • Setting of infection (community-acquired vs. healthcare-associated) 1
  • Local epidemiology and resistance patterns 1

• For native valve endocarditis (NVE), empiric regimens should cover:

  • Staphylococci (including MRSA)
  • Streptococci
  • Enterococci 1

• For early prosthetic valve endocarditis (PVE), cover:

  • Methicillin-resistant staphylococci
  • Enterococci
  • Non-HACEK gram-negative pathogens 1

Pathogen-Specific Treatment

Streptococcal Endocarditis

• Penicillin-sensitive viridans streptococci: Penicillin G or ceftriaxone for 4 weeks 4
• Alternative: Combined penicillin and streptomycin for 2 weeks 4

Enterococcal Endocarditis

• Combination therapy with penicillin/ampicillin plus gentamicin for 4-6 weeks 4
• Vancomycin for penicillin-resistant strains 5
• Vancomycin has been reported effective for endocarditis caused by enterococci only when combined with an aminoglycoside 5

Staphylococcal Endocarditis

• Native valve: Nafcillin, oxacillin, or cefazolin for methicillin-susceptible strains for 4-6 weeks 4
• For methicillin-resistant strains: Vancomycin 5
• Prosthetic valve: Combination therapy with rifampin, gentamicin, and either nafcillin/oxacillin or vancomycin based on susceptibility 1
• Vancomycin has been used successfully in combination with rifampin, an aminoglycoside, or both in early-onset prosthetic valve endocarditis caused by S. epidermidis 5

HACEK Organisms

• Ceftriaxone 2g/24h IV/IM for 4 weeks in native valve endocarditis and 6 weeks in prosthetic valve endocarditis 3
• Alternative: Ampicillin-sulbactam 12g/24h IV in 4 equally divided doses for 4 weeks 3
• For patients unable to tolerate cephalosporins and ampicillin: Ciprofloxacin 1000mg/24h PO or 800mg/24h IV in 2 equally divided doses 3

Non-HACEK Gram-Negative Bacteria

• Early surgery plus long-term (at least 6 weeks) therapy with bactericidal combinations of beta-lactams and aminoglycosides 3
• Sometimes additional quinolones or cotrimoxazole may be needed 3
• In vitro bactericidal tests and monitoring of serum antibiotic concentrations are helpful 3

Blood Culture-Negative Endocarditis

• Treatment depends on suspected pathogen (see table below) 3
• Consultation with an ID specialist from the Endocarditis Team is recommended 3

Pathogen	Treatment
Brucella spp.	Doxycycline (200 mg/24h) plus cotrimoxazole (960 mg/12h) plus rifampin (300-600 mg/24h) for ≥3-6 months orally [3]
C. burnetii (Q fever)	Doxycycline (200 mg/24h) plus hydroxychloroquine (200-600 mg/24h) orally for >18 months [3]
Bartonella spp.	Doxycycline 100 mg/12h orally for 4 weeks plus gentamicin (3 mg/24h) IV for 2 weeks [3]
Legionella spp.	Doxycycline (200 mg/24h) plus hydroxychloroquine (200-600 mg/24h) orally for ≥18 months [3]

Fungal Endocarditis

• Combined antifungal administration and surgical valve replacement 3
• Mortality is very high (>50%) 3
• Most common in prosthetic valve endocarditis and IV drug users 3

Duration of Therapy

• Standard duration is 4-6 weeks of parenteral therapy 6
• Bactericidal antibiotics in high doses given intravenously 2
• Monitoring of antibiotic levels (particularly for vancomycin and aminoglycosides) is essential 1

Surgical Management

• Approximately 50% of endocarditis patients require surgical intervention 1
• Main indications for surgery:
  • Heart failure due to valve dysfunction 1
  • Uncontrolled infection (abscess, false aneurysm, fistula, enlarging vegetation) 1
  • Prevention of systemic embolism 1
  • Fungal or multiresistant organism infections 1
  • Persistent positive blood cultures despite appropriate antibiotic therapy 1

Special Considerations

• Gentamicin is effective when used in conjunction with a penicillin-type drug for treatment of endocarditis caused by group D streptococci 7
• For urgent cases where empiric therapy is needed before pathogen identification, a combination of aqueous penicillin G, nafcillin, and gentamicin can be effective 4
• Hospitalization is often mandatory, but outpatient parenteral antibiotic therapy (OPAT) may be considered for stable patients with uncomplicated infections 8, 1

Pitfalls and Caveats

• Avoid OPAT in patients with heart failure, concerning echocardiographic features, neurological signs, or renal impairment 1
• Only antibiotics that have been proven effective against endocarditis should be used 2
• Aminoglycosides have potential toxic effects that dictate limitation or avoidance if possible 3
• Consultation with an infectious diseases specialist is recommended, especially for BCNIE cases 3