What is the recommended treatment for endocarditis?

Treatment of Infective Endocarditis

Initiate empiric antibiotic therapy immediately after obtaining three sets of blood cultures at 30-minute intervals, with regimen selection based on whether the infection involves a native or prosthetic valve, the acquisition setting (community vs. healthcare-associated), and local resistance patterns. 1

Empiric Therapy Before Pathogen Identification

Community-Acquired Native Valve Endocarditis

• Administer 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, 2
• For penicillin-allergic patients, substitute vancomycin 30-60 mg/kg/day IV in 2-3 doses plus gentamicin 3 mg/kg/day IV or IM in 1 dose 1, 2

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

• Use 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 IV or orally in 2-3 divided doses 1
• Start rifampin 3-5 days after vancomycin and gentamicin 1

Pathogen-Specific Treatment (After Identification)

Streptococcal Endocarditis (Penicillin-Susceptible, MIC ≤0.1 mg/L)

Standard 4-week regimen:

• Penicillin G 12-18 million units/day IV in 4-6 doses OR amoxicillin 100-200 mg/kg/day IV in 4-6 doses OR ceftriaxone 2 g/day IV or IM in 1 dose 1

Shortened 2-week regimen (for uncomplicated native valve endocarditis only):

• Penicillin G 12-18 million units/day IV OR amoxicillin 100-200 mg/kg/day IV OR ceftriaxone 2 g/day IV PLUS gentamicin 3 mg/kg/day IV or IM in 1 dose 1
• This 2-week regimen achieves cure rates of at least 98% with only 0.7% relapse risk 3

For prosthetic valve endocarditis: Extend therapy to 6 weeks 1

Streptococcal Endocarditis (Relatively Resistant, MIC 0.25-2 mg/L)

• Penicillin G 24 million units/day IV OR amoxicillin 200 mg/kg/day IV OR ceftriaxone 2 g/day IV PLUS gentamicin 3 mg/kg/day IV for the entire 4-week course 1
• Extend to 6 weeks for prosthetic valve involvement 1

Enterococcal Endocarditis

For susceptible strains on native valves:

• Penicillin G or ampicillin PLUS gentamicin for 4-6 weeks 1
• Patients with symptoms <3 months or aortic valve involvement: treat for 4 weeks 3, 4
• Patients with symptoms >3 months or mitral valve involvement: treat for 6 weeks (due to 44% relapse rate vs. 0% with shorter symptom duration) 3, 4

For β-lactam intolerant patients:

• Vancomycin combined with gentamicin for 6 weeks 1

Critical dosing consideration: Use gentamicin ≤3 mg/kg/day to minimize nephrotoxicity (100% nephrotoxicity at higher doses vs. 20% at ≤3 mg/kg/day) 3

For aminoglycoside-resistant E. faecalis:

• Ampicillin plus ceftriaxone (ceftriaxone exploits synergy despite enterococcal resistance to cephalosporins alone) 1

Always obtain infectious disease consultation for enterococcal endocarditis 1

Staphylococcal Endocarditis

Methicillin-susceptible S. aureus (native valve):

• Nafcillin or oxacillin 2 g IV every 4 hours for 4-6 weeks 5, 6
• Optional: Add gentamicin 1 mg/kg IV every 8 hours for first 3-5 days to accelerate bacteremia clearance 5, 6

Methicillin-resistant S. aureus (native valve):

• Vancomycin 30 mg/kg/day IV in 2-4 doses for minimum 6 weeks 5, 6
• Target vancomycin trough levels 10-15 mg/L (some experts recommend 15-20 mg/L for staphylococcal infections) 1

Prosthetic valve staphylococcal endocarditis:

• Three-drug regimen: nafcillin/oxacillin (or vancomycin if methicillin-resistant) PLUS gentamicin PLUS rifampin 600-900 mg/day orally for ≥6 weeks 5, 6

Right-sided endocarditis (uncomplicated):

• May use shortened 2-week treatment course 6

HACEK Organisms

• Ceftriaxone 2 g/day IV for 4 weeks (native valve) or 6 weeks (prosthetic valve) 2

Non-HACEK Gram-Negative Bacteria

• Early surgery PLUS long-term therapy (≥6 weeks) with bactericidal combinations of beta-lactams and aminoglycosides 1, 7
• Consider adding quinolones or cotrimoxazole based on susceptibility 1
• Consult infectious disease specialist 1

Fungal Endocarditis

• Combined antifungal therapy PLUS surgical valve replacement (mortality >50% without surgery) 1, 7

Blood Culture-Negative Endocarditis

For specific pathogens identified by serology/PCR:

• Bartonella: Doxycycline 100 mg every 12 hours orally for 4 weeks PLUS gentamicin 3 mg/24 hours IV for 2 weeks 1
• C. burnetii (Q fever): Doxycycline 200 mg/24 hours PLUS hydroxychloroquine 200-600 mg/24 hours orally for >18 months (monitor hydroxychloroquine levels) 1
• Brucella: Doxycycline 200 mg/24 hours PLUS cotrimoxazole 960 mg every 12 hours PLUS rifampin 300-600 mg/24 hours orally for ≥3-6 months 1

Always consult infectious disease specialist for blood culture-negative cases 1, 7

Monitoring and Safety

• Monitor vancomycin and gentamicin levels weekly along with renal function tests due to nephrotoxicity risk 1, 2
• Gentamicin trough levels should be <1 mg/L; peak levels 10-12 mg/L 1
• Vancomycin trough levels should be 10-15 mg/L (15-20 mg/L for staphylococcal infections per some experts) 1
• Repeat blood cultures until sterile to confirm treatment adequacy 2

Surgical Indications

Approximately 50% of endocarditis patients require surgery 7

Immediate surgical consultation for:

• Heart failure due to valve dysfunction 7
• Uncontrolled infection (abscess, false aneurysm, fistula, enlarging vegetation) 7
• Prevention of systemic embolism (particularly with large vegetations >10 mm) 7
• Fungal or multiresistant organism infections 7
• Persistent positive blood cultures despite appropriate antibiotics 7

Multidisciplinary Management

• All endocarditis cases should be managed by an "Endocarditis Team" including infectious disease specialists, cardiologists, cardiac surgeons, and microbiologists 7
• Complex cases (rare pathogens, blood culture-negative, multidrug-resistant organisms) require team discussion 7

Outpatient Parenteral Antibiotic Therapy (OPAT)

Consider OPAT only after initial 2-week critical phase for stable patients with:

• Uncomplicated native valve infection caused by oral streptococci or S. bovis 7
• No heart failure, concerning echocardiographic features, neurological signs, or renal impairment 7
• Adequate patient/staff education and physician-directed program 7