What is the treatment for infective endocarditis?

Treatment of Infective Endocarditis

Treatment of infective endocarditis requires prompt initiation of prolonged intravenous bactericidal antibiotics (4-6 weeks) tailored to the specific pathogen, combined with early surgical consultation in approximately 50% of cases. 1

Initial Diagnostic Steps Before Treatment

Obtain three sets of blood cultures at 30-minute intervals before starting any antibiotics to maximize pathogen identification and guide targeted therapy. 2, 1 This is critical because prior antibiotic exposure significantly reduces the diagnostic yield of both blood cultures and valve tissue samples. 3

Empirical Antibiotic Therapy

Treatment must be started promptly after blood cultures are drawn, even before pathogen identification. 2, 1 The choice of empirical regimen depends on three key factors:

Factor 1: Native vs. Prosthetic Valve

• Native valve endocarditis (NVE): Cover staphylococci (including MRSA), streptococci, and enterococci 1
• Early prosthetic valve endocarditis (PVE, <1 year post-surgery): Add coverage for methicillin-resistant staphylococci and consider gram-negative coverage if within 2 months of surgery 2, 1
• Late PVE (>1 year post-surgery): Treat similarly to native valve endocarditis 2

Factor 2: Prior Antibiotic Exposure

• If antibiotics given before cultures: For acute presentations, prioritize S. aureus coverage; for subacute presentations, use ampicillin-sulbactam 3g IV every 6 hours plus gentamicin 1 mg/kg IV every 8 hours to cover staphylococci, streptococci, enterococci, and HACEK organisms 2
• No prior antibiotics: Follow standard empirical regimens based on valve type 2, 1

Factor 3: Clinical Setting

• Community-acquired: Standard empirical coverage 2, 1
• Healthcare-associated or nosocomial: Broaden coverage for resistant organisms and consider local antibiogram patterns 2, 1

Pathogen-Specific Therapy (Once Identified)

Streptococcal Endocarditis

Use penicillin, ceftriaxone, or vancomycin (for penicillin-allergic patients) for 4-6 weeks. 1

Enterococcal Endocarditis

Combination therapy is mandatory: ampicillin 12g/24h IV plus gentamicin 3mg/kg/24h IV for synergy. 1, 4, 5 Vancomycin replaces ampicillin for resistant strains. 1, 4

Staphylococcal Endocarditis

• Native valve, methicillin-susceptible: Nafcillin, oxacillin, or cefazolin for 6 weeks 1
• Native valve, methicillin-resistant: Vancomycin for 6 weeks 1, 4
• Prosthetic valve: Triple therapy with rifampin + gentamicin + either nafcillin/oxacillin (MSSA) or vancomycin (MRSA) for 6 weeks 1, 4

HACEK Organisms

Ceftriaxone 2g/24h IV for 4 weeks (native valve) or 6 weeks (prosthetic valve). 2, 1 Ampicillin-sulbactam is an alternative. 2

Non-HACEK Gram-Negative Bacteria

Early surgery plus at least 6 weeks of combination therapy with beta-lactams and aminoglycosides, sometimes adding quinolones or cotrimoxazole. 2, 1 These cases require infectious disease consultation. 2, 1

Fungal Endocarditis

Combined antifungal therapy plus surgical valve replacement is mandatory due to mortality exceeding 50%. 2, 1 Medical therapy alone is inadequate. 2, 1

Blood Culture-Negative Endocarditis (BCNIE)

Consult infectious disease specialists immediately. 2, 1 Specific pathogen-directed therapy includes:

• Brucella: Doxycycline 200mg/24h + cotrimoxazole 960mg/12h + rifampin 300-600mg/24h orally for ≥3-6 months 2
• C. burnetii (Q fever): Doxycycline 200mg/24h + hydroxychloroquine 200-600mg/24h orally for >18 months 2
• Bartonella: Doxycycline 100mg/12h orally for 4 weeks + gentamicin 3mg/24h IV for 2 weeks 2
• T. whipplei (Whipple's disease): Doxycycline 200mg/24h + hydroxychloroquine 200-600mg/24h orally for ≥18 months; add sulfadiazine 1.5g/6h if CNS involvement 2

Critical Treatment Principles

Bactericidal Therapy Requirements

• High-dose intravenous administration to ensure complete bioavailability and adequate penetration into vegetations 6, 7
• Combination therapy with synergistic activity (typically cell-wall-active agent plus aminoglycoside) 2, 7
• Monitor antibiotic levels for vancomycin and aminoglycosides to optimize efficacy and minimize toxicity 1, 7

Duration of Therapy

• Standard duration: 4-6 weeks of parenteral therapy to sterilize vegetations and prevent relapse 1, 6, 7
• Prosthetic valve infections require 6 weeks minimum 2, 1

Surgical Indications

Approximately 50% of patients require surgery. 1 Early cardiac surgery consultation is essential. 1 Absolute indications include:

• Heart failure from severe valve dysfunction 1
• Uncontrolled infection: abscess, false aneurysm, fistula, enlarging vegetation 1
• Prevention of systemic embolism in high-risk vegetations 1
• Fungal or multiresistant organism infections 1
• Persistent bacteremia despite appropriate antibiotics 1

Outpatient Parenteral Antibiotic Therapy (OPAT)

OPAT is only appropriate for stable patients with uncomplicated native valve infections caused by oral streptococci or S. bovis after the critical first 2 weeks. 1

Absolute contraindications to OPAT: 1

• Heart failure
• Concerning echocardiographic features (large vegetations, abscess)
• Neurological complications
• Renal impairment
• Prosthetic valve involvement

Multidisciplinary Management

All cases should be managed by an "Endocarditis Team" including infectious disease specialists, cardiologists, cardiac surgeons, and microbiologists. 1 Complex cases involving rare pathogens, BCNIE, or multidrug-resistant organisms mandate team discussion. 2, 1

Common Pitfalls to Avoid

• Never delay blood cultures to start antibiotics in stable patients; obtain cultures first 2, 1
• Do not use oral antibiotics for initial therapy; parenteral administration is mandatory 6, 8, 7
• Avoid monotherapy for enterococcal endocarditis; aminoglycoside combination is essential 1, 4
• Do not attempt medical therapy alone for fungal endocarditis; surgery is required 2, 1
• Recognize that valve cultures become negative after 2 weeks of antibiotics, though PCR may remain positive 3