What is the treatment for infective endocarditis?

Treatment of Infective Endocarditis

Empirical Antibiotic Therapy

For community-acquired native valve endocarditis, start ampicillin 12 g/day IV in 4-6 divided doses plus (flu)cloxacillin/oxacillin 12 g/day IV in 4-6 divided doses plus gentamicin 3 mg/kg/day IV or IM in a single daily dose after obtaining three sets of blood cultures at 30-minute intervals. 1, 2

Native Valve Endocarditis (Community-Acquired)

• First-line regimen: Ampicillin 12 g/day IV in 4-6 doses + (flu)cloxacillin/oxacillin 12 g/day IV in 4-6 doses + gentamicin 3 mg/kg/day IV or IM in 1 dose 1, 2
• Penicillin-allergic patients: Vancomycin 30-60 mg/kg/day IV in 2-3 doses + gentamicin 3 mg/kg/day IV or IM in 1 dose 1, 2
• This empirical regimen covers the most common pathogens: staphylococci, streptococci, and enterococci 3

Prosthetic Valve Endocarditis or Healthcare-Associated Infection

• Standard regimen: Vancomycin 30 mg/kg/day IV in 2 doses + gentamicin 3 mg/kg/day IV or IM in 1 dose + rifampin 900-1200 mg IV or orally in 2-3 divided doses 1, 2
• This triple-drug combination is necessary to cover methicillin-resistant staphylococci, enterococci, and non-HACEK gram-negative pathogens 3
• Rifampin is critical for prosthetic device infections as it eradicates bacteria attached to foreign material 4

Pathogen-Specific Therapy (After Culture Results)

Streptococcal Endocarditis (Penicillin-Susceptible)

For viridans streptococci with MIC ≤0.1 mg/L, use penicillin G 18-30 million units/24h IV continuously or in 6 divided doses (or ampicillin 12 g/24h IV in 6 doses) plus gentamicin 3 mg/kg/day IV/IM in 3 divided doses for 4 weeks in native valve endocarditis. 4

• Duration: 4 weeks for patients with symptoms <3 months; 6 weeks for symptoms ≥3 months 4
• Prosthetic valve: Minimum 6 weeks of therapy 4
• Gentamicin peak levels should reach 3 μg/mL and trough <1 μg/mL 4
• Alternative for outpatient therapy: Ceftriaxone 2 g/day IV 4

Enterococcal Endocarditis

Treat enterococcal endocarditis with ampicillin 12 g/24h IV in 6 divided doses (or penicillin G 18-30 million units/24h IV) plus gentamicin 3 mg/kg/day IV/IM in 3 divided doses for 4-6 weeks. 4

• Duration: 4 weeks for symptoms <3 months; 6 weeks for symptoms ≥3 months or prosthetic valve 4, 5
• Vancomycin should only be used if the patient cannot tolerate penicillin/ampicillin, as penicillin-gentamicin combinations are more active than vancomycin-gentamicin 4
• Critical: Do NOT use once-daily aminoglycoside dosing for enterococcal endocarditis—use multiple divided doses 4
• For vancomycin-resistant enterococci, consultation with infectious disease specialist is mandatory 3

Staphylococcal Native Valve Endocarditis

For methicillin-susceptible S. aureus, use (flu)cloxacillin/oxacillin 12 g/day IV in 4-6 doses for 4-6 weeks; for methicillin-resistant strains, use vancomycin 30 mg/kg/day IV in 2 doses for 4-6 weeks. 4, 3

• Optional addition of gentamicin 3 mg/kg/day IV/IM in 2-3 doses for 3-5 days (clinical benefit not formally demonstrated but associated with increased toxicity) 4
• Vancomycin trough levels should be 25-30 mg/L 4
• Alternative for S. aureus bacteremia with right-sided endocarditis: Daptomycin 6 mg/kg/day IV 6

Staphylococcal Prosthetic Valve Endocarditis

For prosthetic valve staphylococcal endocarditis, use (flu)cloxacillin/oxacillin 12 g/day IV in 4-6 doses plus rifampin 1200 mg/day IV or orally in 2 doses plus gentamicin 3 mg/kg/day IV/IM in 2-3 doses for at least 6 weeks. 4

• For methicillin-resistant strains: Vancomycin 30 mg/kg/day IV in 2 doses + rifampin 1200 mg/day + gentamicin 3 mg/kg/day for ≥6 weeks 4
• Rifampin must always be combined with another effective antistaphylococcal drug to prevent resistance 4
• Rifampin increases hepatic metabolism of warfarin and other drugs—monitor closely 4

HACEK Organisms

• Treatment: Ceftriaxone 2 g/day IV for 4 weeks in native valve endocarditis and 6 weeks in prosthetic valve endocarditis 1, 3
• Alternative: Ampicillin 12 g/day IV in 4-6 doses plus gentamicin 3 mg/kg/day for 4-6 weeks 1

Non-HACEK Gram-Negative Bacteria

• Treatment: Combination of beta-lactams and aminoglycosides for at least 6 weeks 1, 3
• Consider adding quinolones or cotrimoxazole based on susceptibility testing 1
• Early surgical consultation is critical due to high failure rates with medical therapy alone 3

Fungal Endocarditis

• Treatment: Combined antifungal therapy PLUS surgical valve replacement 1, 3
• Medical therapy alone is inadequate—mortality exceeds 50% despite aggressive treatment 1, 3

Critical Management Principles

Blood Culture Collection

• Always obtain three sets of blood cultures at 30-minute intervals BEFORE starting antibiotics 1, 2, 3
• Starting empirical antibiotics without cultures leads to blood culture-negative endocarditis, making diagnosis and treatment significantly more difficult 2

When to Start Empirical Therapy

• Start empirical therapy immediately after blood cultures in patients with severe sepsis, acute heart failure, or severe systemic signs of infection 2
• In stable patients without life-threatening complications, delay antibiotics until cultures are obtained 2

Monitoring Requirements

• Aminoglycoside levels: For gentamicin given in divided doses, peak (1 hour post-dose) should be 3 μg/mL and trough <1 μg/mL 4
• Vancomycin levels: Trough should be 25-30 mg/L (some guidelines suggest 10-15 mg/L) 4
• Monitor renal function at least weekly when using aminoglycosides 4, 3
• Obtain follow-up blood cultures to document clearance of bacteremia 1

Duration of Therapy

• Standard duration: 4-6 weeks of parenteral therapy to prevent treatment failure or relapse 3, 7
• The clock starts from the first day of appropriate therapy (after culture results), not from the first day of empirical therapy 7
• Prosthetic valve endocarditis requires minimum 6 weeks regardless of pathogen 4

Surgical Indications

Approximately 50% of patients with infective endocarditis require surgical intervention—early cardiac surgery consultation is essential. 2, 3

Main Indications for Surgery

• Heart failure due to severe valve dysfunction 3
• Uncontrolled infection (abscess, false aneurysm, fistula, enlarging vegetation) 3
• Prevention of systemic embolism (particularly large mobile vegetations >10 mm) 3
• Fungal or multidrug-resistant organism infections 3
• Persistent positive blood cultures despite appropriate antibiotic therapy 3

Multidisciplinary Approach

• Management by an "Endocarditis Team" is strongly recommended, including infectious disease specialists, cardiologists, cardiac surgeons, and microbiologists 3
• Complex cases (rare pathogens, blood culture-negative endocarditis, multidrug-resistant organisms) should be discussed by the team 3

Important Caveats

• Daptomycin is NOT indicated for left-sided endocarditis due to poor outcomes in clinical trials 6
• Daptomycin is NOT indicated for pneumonia as it is inactivated by pulmonary surfactant 6
• Gentamicin addition to staphylococcal regimens increases nephrotoxicity and ototoxicity without proven clinical benefit—use is optional and should be limited to 3-5 days if used 4
• Outpatient parenteral antibiotic therapy should only be considered for stable patients with uncomplicated native valve endocarditis caused by oral streptococci after the critical first 2 weeks 3