What is the treatment for infective endocarditis?

Treatment of Infective Endocarditis

Infective endocarditis requires immediate bactericidal antibiotic therapy tailored to the causative organism, valve type (native vs. prosthetic), and clinical setting, with treatment initiated promptly after obtaining three sets of blood cultures at 30-minute intervals. 1

Immediate Initial Steps

• Draw three sets of blood cultures at 30-minute intervals before starting antibiotics 2, 1
• Start empirical therapy immediately after blood cultures are obtained in acutely ill patients 1
• Consult an endocarditis team or infectious disease specialist for all cases 2, 1

Empirical Therapy (Before Organism Identification)

Native Valve Endocarditis

• Ampicillin 12 g/day IV in 4-6 divided doses PLUS gentamicin 3 mg/kg/day IV or IM once daily 1
• Alternative: (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 doses plus gentamicin 3 mg/kg/day 1

Prosthetic Valve Endocarditis

• Vancomycin 30 mg/kg/day IV in 2 divided doses PLUS gentamicin 3 mg/kg/day IV or IM once daily PLUS rifampin 900-1200 mg/day IV or oral in 2-3 divided doses 1
• This triple-drug regimen is essential for prosthetic valves given the higher mortality and complexity 2, 1

Definitive Therapy Based on Identified Organism

Methicillin-Susceptible Staphylococcus aureus (MSSA)

• (Flu)cloxacillin or oxacillin 12 g/day IV in 4-6 divided doses for 4-6 weeks 1
• Do NOT add gentamicin for MSSA native valve endocarditis—it provides no clinical benefit and increases nephrotoxicity 1
• For right-sided endocarditis: Daptomycin is FDA-approved at appropriate dosing 3

Enterococcal Endocarditis

• Ampicillin (or amoxicillin) 12 g/day IV in 4-6 divided doses PLUS gentamicin 3 mg/kg/day IV in 2-3 divided doses for 4-6 weeks 1
• This synergistic bactericidal combination is mandatory for enterococci 4, 5

HACEK Organisms

• Ceftriaxone 2 g/day IV for 4 weeks (native valve) or 6 weeks (prosthetic valve) 2
• Alternative if beta-lactamase negative: Ampicillin 12 g/day IV plus gentamicin 3 mg/kg/day for 4-6 weeks 2
• Ciprofloxacin 400 mg IV every 8-12 hours is a less-validated alternative 2

Non-HACEK Gram-Negative Bacteria

• Early surgery PLUS long-term therapy (≥6 weeks) with bactericidal combinations of beta-lactams and aminoglycosides 2
• Consider adding quinolones or cotrimoxazole based on susceptibility 2
• These rare cases mandate endocarditis team discussion given 1.8% incidence and high severity 2

Blood Culture-Negative Endocarditis

Prior Antibiotic Use with Subacute Presentation

• Ampicillin-sulbactam 3 g IV every 6 hours PLUS gentamicin 1 mg/kg IV or IM every 8 hours 1

Specific Fastidious Organisms (Table-Based Approach)

Bartonella species:

• Doxycycline 100 mg every 12 hours orally for 4 weeks PLUS gentamicin 3 mg/24 hours IV for 2 weeks 2

Coxiella burnetii (Q fever):

• Doxycycline 200 mg/24 hours PLUS hydroxychloroquine 200-600 mg/24 hours orally for >18 months 2
• Treatment success defined as anti-phase I IgG titer <1:200 2

Brucella species:

• Doxycycline 200 mg/24 hours PLUS cotrimoxazole 960 mg every 12 hours PLUS rifampin 300-600 mg/24 hours orally for ≥3-6 months 2, 6
• Treatment success defined as antibody titer <1:60 2, 6

Tropheryma whipplei (Whipple's disease):

• Doxycycline 200 mg/24 hours PLUS hydroxychloroquine 200-600 mg/24 hours orally for ≥18 months 2

• Mandatory infectious disease consultation for all blood culture-negative cases 2, 1

Fungal Endocarditis

• Combined antifungal therapy PLUS surgical valve replacement 2, 1
• Mortality exceeds 50% despite aggressive treatment 2
• Most common in prosthetic valve endocarditis, IV drug users, and immunocompromised patients 2
• Candida and Aspergillus species predominate 2

Treatment Duration

Native Valve Endocarditis

• 4 weeks for most pathogens 1
• Extend based on pathogen and clinical response 1

Prosthetic Valve Endocarditis

• Minimum 6 weeks for all cases 1
• Extend if complications develop or slow response 1

Critical Monitoring Requirements

• Regular clinical assessment with follow-up blood cultures 1
• Monitor renal function when using aminoglycosides 1
• Therapeutic drug monitoring for vancomycin (trough 15-20 mcg/mL) and gentamicin 1
• Serum bactericidal titers have poor predictive value and lack standardization 4

Aminoglycoside Use: Modern Approach

• Limit aminoglycosides to maximum 2 weeks to reduce nephrotoxicity and ototoxicity 1
• Administer once daily dosing (concentration-dependent killing with post-antibiotic effect) 1, 4
• Aminoglycoside use has decreased dramatically over the past 20 years 1
• Never add gentamicin to MSSA native valve endocarditis—no benefit, only harm 1

Surgical Intervention

• Surgery is required in approximately 50% of endocarditis cases and can be life-saving 1, 6

Absolute indications for surgery:

• Heart failure due to severe valve dysfunction 6

• Uncontrolled infection with abscess formation 6

• Persistent positive blood cultures despite appropriate therapy 6

• Prevention of systemic embolism in high-risk cases 6

• Surgical intervention is crucial for maximizing outcomes in Staphylococcus aureus prosthetic valve endocarditis 1

• Independent predictors of mortality include inotrope dependence, annular abscess, pulmonary edema, and staphylococcal infection 7

Critical Pitfalls to Avoid

• Never delay blood cultures to start antibiotics—obtain three sets first 2, 1
• Do not use oral antibiotics initially—parenteral administration is mandatory for adequate bioavailability and vegetation penetration 4, 8
• Do not use trimethoprim alone for Brucella—cotrimoxazole (trimethoprim-sulfamethoxazole) is required 6
• Avoid short treatment courses (<3-6 months) for Brucella endocarditis—associated with treatment failure 6
• Do not use daptomycin for pneumonia or left-sided endocarditis—FDA contraindicated 3
• Daptomycin has not been studied in prosthetic valve endocarditis 3
• Pre-operative antimicrobial treatment >2 weeks renders valve cultures negative (though PCR may remain positive in 53% of cases) 9