What is the treatment for endocarditis?

Treatment of Infective Endocarditis

Infective endocarditis requires immediate bactericidal antibiotic therapy tailored to the causative organism, valve type (native vs. prosthetic), and infection setting, with treatment duration of 4-6 weeks for native valves and at least 6 weeks for prosthetic valves. 1, 2

Initial Management Steps

Before initiating antibiotics, obtain three sets of blood cultures at 30-minute intervals, then start empirical therapy immediately in acutely ill patients without waiting for culture results. 1, 3, 2 Consultation with an infectious disease specialist or endocarditis team is strongly recommended for all cases. 1, 3, 2

Empirical Antibiotic Regimens (Before Pathogen Identification)

Community-Acquired Native Valve Endocarditis

First-line regimen:

• 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, 3, 2

For penicillin-allergic patients:

• Vancomycin 30-60 mg/kg/day IV in 2-3 doses PLUS
• Gentamicin 3 mg/kg/day IV or IM in 1 dose 1, 3, 2

Early Prosthetic Valve Endocarditis (<12 months post-surgery) or Healthcare-Associated Endocarditis

Standard triple therapy:

• 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/day IV or oral in 2-3 divided doses 1, 3, 2

Critical timing: Start rifampin 3-5 days after vancomycin and gentamicin have been initiated. 3

Pathogen-Specific Definitive Therapy

Methicillin-Susceptible Staphylococcus aureus (MSSA)

Native valve:

• (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses for 4-6 weeks 2, 4
• Do NOT add gentamicin - it provides no clinical benefit and increases nephrotoxicity 2

Prosthetic valve:

• Same beta-lactam PLUS gentamicin PLUS rifampin for at least 6 weeks 2, 4

Methicillin-Resistant Staphylococcus aureus (MRSA)

• Vancomycin 30 mg/kg/day IV in 2-4 doses for 4-6 weeks (native valve) or 6+ weeks (prosthetic valve) 5, 4
• Consider adding rifampin 600-900 mg/day orally, particularly for prosthetic valves 4

Enterococcal Endocarditis

For fully penicillin-susceptible strains:

• Ampicillin (or amoxicillin) 12 g/day IV in 4-6 doses PLUS
• Gentamicin 3 mg/kg/day IV in 2-3 doses for 4-6 weeks 2, 6

Key principle: Synergistic bactericidal combination is essential; vancomycin alone is ineffective. 5, 6

Streptococcal Endocarditis (Viridans Group, S. bovis)

Penicillin-sensitive strains:

• Aqueous penicillin G 20 million units/day IV for 4 weeks alone, OR
• Penicillin G PLUS streptomycin for 2 weeks (shorter course option) 6

Blood Culture-Negative Endocarditis

Empirical coverage for atypical organisms:

• Ampicillin-sulbactam 3 g IV every 6 hours PLUS gentamicin 1 mg/kg IV every 8 hours 2
• Mandatory infectious disease consultation 1, 3, 2

Specific pathogen-directed therapy (if identified):

• Bartonella: Doxycycline 100 mg q12h orally for 4 weeks PLUS gentamicin 3 mg/24h IV for 2 weeks 1
• Brucella: Doxycycline 200 mg/24h PLUS cotrimoxazole 960 mg q12h PLUS rifampin 300-600 mg/24h for ≥3-6 months orally 1
• C. burnetii (Q fever): Doxycycline 200 mg/24h PLUS hydroxychloroquine 200-600 mg/24h orally for >18 months 1

HACEK Organisms

• Ceftriaxone 2 g/day IV for 4 weeks (native valve) or 6 weeks (prosthetic valve) 3
• Alternative: Ampicillin 12 g/day IV in 4-6 doses PLUS gentamicin 3 mg/kg/day for 4-6 weeks 3

Non-HACEK Gram-Negative Bacteria

• Beta-lactam PLUS aminoglycoside for at least 6 weeks 1, 3
• Consider adding quinolones or cotrimoxazole based on susceptibility 1, 3
• Early surgery is typically required 1

Fungal Endocarditis

• Combined antifungal therapy PLUS surgical valve replacement 1, 3, 2
• Mortality exceeds 50% despite aggressive treatment 1, 3, 2

Treatment Duration

Native valve endocarditis: 4 weeks for most pathogens, extending to 6 weeks for complicated cases 2, 6

Prosthetic valve endocarditis: Minimum 6 weeks for all cases, with extension for complications or slow response 2

Right-sided endocarditis (uncomplicated): May consider shortened 2-week course for selected cases 4

Monitoring Requirements

• Regular clinical assessment and repeat blood cultures to document clearance 7, 3
• Monitor renal function when using aminoglycosides 3, 2
• Therapeutic drug monitoring for vancomycin (target trough 15-20 mcg/mL) and gentamicin 3, 2
• For Q fever: Monitor anti-phase I IgG titers (success <1:200) and IgA/IgM titers (success <1:50) 1, 7
• For Brucella: Monitor antibody titers (success <1:60) 1, 7

Critical Aminoglycoside Considerations

Limit aminoglycoside use to minimize toxicity:

• Use once-daily dosing 2
• Maximum duration of 2 weeks 2
• Do NOT add to MSSA native valve endocarditis - no benefit, increased harm 2

Role of Oral Switch Therapy

Recent evidence supports early oral switch in selected clinically stable patients, showing reduced relapse rates (OR 0.54) compared to continued IV therapy, with no difference in mortality or treatment failure. 8 However, this approach requires careful patient selection and close monitoring. 9, 8

Surgical Intervention

Surgery is often life-saving and should be considered early for:

• Prosthetic valve endocarditis with complications 2
• Severe valve dysfunction 2
• Perivalvular abscess formation 2
• Fungal endocarditis 1, 2
• Persistent bacteremia despite appropriate antibiotics 2

Common Pitfalls to Avoid

• Delayed antibiotic initiation after blood cultures reduces treatment success 7
• Inadequate treatment duration - complete eradication requires full 4-6 week courses due to high bacterial densities in vegetations 7
• Adding gentamicin to MSSA native valve cases - increases nephrotoxicity without benefit 2
• Treating enterococcal endocarditis with vancomycin alone - requires synergistic combination 5, 6
• Failing to adjust empirical therapy once susceptibilities are available 5