What is the recommended treatment for endocarditis?

Endocarditis Treatment

For community-acquired native valve endocarditis, initiate 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/IM (single daily dose) for 4-6 weeks. 1, 2

Initial Management and Diagnosis

Before starting antibiotics, obtain three sets of blood cultures at 30-minute intervals to maximize pathogen identification, though empirical therapy should begin immediately after cultures are drawn in acutely ill patients. 2, 3 Perform transthoracic echocardiography (TTE) as first-line imaging, followed by transesophageal echocardiography (TOE) if TTE is non-diagnostic or if prosthetic valves/devices are present. 1

All patients with complicated infective endocarditis should be managed by a multidisciplinary Endocarditis Team including infectious disease specialists, cardiologists, microbiologists, and cardiac surgeons at a reference center with immediate surgical capabilities. 1, 3

Empirical Antibiotic Regimens

Community-Acquired Native Valve Endocarditis

First-line regimen:

• Ampicillin: 12 g/day IV in 4-6 doses 1, 2
• (Flu)cloxacillin or oxacillin: 12 g/day IV in 4-6 doses 1, 2
• Gentamicin: 3 mg/kg/day IV or IM in 1 dose 1, 2

For penicillin-allergic patients:

• Vancomycin: 30-60 mg/kg/day IV in 2-3 doses 1, 2, 4
• Gentamicin: 3 mg/kg/day IV or IM in 1 dose 1, 2, 4

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

Standard regimen:

• Vancomycin: 30 mg/kg/day IV in 2 doses 1, 2
• Gentamicin: 3 mg/kg/day IV or IM in 1 dose 1, 2
• Rifampin: 900-1200 mg IV or orally in 2-3 divided doses (start 3-5 days after vancomycin and gentamicin) 1, 2

Critical caveat: In healthcare-associated native valve endocarditis in settings with MRSA prevalence >5%, some experts recommend combining cloxacillin plus vancomycin until final S. aureus identification. 1

Late Prosthetic Valve Endocarditis (≥12 months post-surgery)

Use the same regimens as native valve endocarditis with the addition of rifampin. 1

Organism-Specific Treatment (Once Identified)

Staphylococcus aureus

Methicillin-susceptible (MSSA):

• Nafcillin or oxacillin: 2 g IV every 4 hours for 4-6 weeks 4, 5, 6
• Optional: Gentamicin 1 mg/kg IV every 8 hours for first 3-5 days 4, 6

Methicillin-resistant (MRSA):

• Vancomycin: 30 mg/kg/day IV in 2-4 doses for minimum 6 weeks 4, 7, 6
• Consider adding rifampin 600-900 mg/day orally for prosthetic valves 6

Streptococcal Endocarditis

Penicillin-sensitive viridans streptococci:

• Penicillin G: 20 million units/day IV for 4 weeks 8
• Alternative: Combined penicillin plus streptomycin for 2 weeks 8

Enterococcal endocarditis:

• Penicillin G or ampicillin: 12 g/day IV in 4-6 doses for 4-6 weeks 1, 3
• Plus gentamicin: 3 mg/kg/day IV/IM for 4-6 weeks 1, 3
• Vancomycin is effective only in combination with an aminoglycoside for enterococci 7

HACEK Organisms

• Ceftriaxone: 2 g/day IV for 4 weeks (native valve) or 6 weeks (prosthetic valve) 1, 2, 4
• Alternative: Ampicillin 12 g/day IV plus gentamicin 3 mg/kg/day for 4-6 weeks 1

Non-HACEK Gram-Negative Bacteria

Requires early surgery plus long-term combination therapy (≥6 weeks):

• Beta-lactams plus aminoglycosides 1, 2, 3
• Consider adding quinolones or cotrimoxazole based on susceptibility 2
• In vitro bactericidal testing and serum antibiotic monitoring may be helpful 1

Fungal Endocarditis

Combined antifungal therapy plus surgical valve replacement is mandatory due to extremely high mortality (>50%). 1, 2, 3 Candida species usually produce positive blood cultures, while Aspergillus causes culture-negative endocarditis. 1

Blood Culture-Negative Endocarditis (BCNIE)

Consultation with an infectious disease specialist is strongly recommended. 1, 2

Specific Pathogens and Treatment

Bartonella species:

• Doxycycline: 100 mg every 12 hours orally for 4 weeks 1
• Plus gentamicin: 3 mg/kg/day IV for 2 weeks 1

Coxiella burnetii (Q fever):

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

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 1

Tropheryma whipplei (Whipple's disease):

• Doxycycline: 200 mg/24 hours plus hydroxychloroquine: 200-600 mg/24 hours orally for ≥18 months 1
• Add sulfadiazine 1.5 g every 6 hours if CNS involvement 1

Surgical Indications (Urgent Surgery Required)

Absolute indications for urgent surgery: 1

• Severe aortic or mitral regurgitation/obstruction causing heart failure symptoms or poor hemodynamic tolerance 1
• Locally uncontrolled infection (abscess, false aneurysm, fistula, enlarging vegetation) 1
• Fungal or multiresistant organism infections 1
• Persistent vegetations >10 mm after ≥1 embolic episode despite appropriate antibiotics 1

Approximately 50% of endocarditis patients require surgical intervention. 3 Early cardiac surgery consultation is essential to determine optimal timing. 3

Treatment Duration and Monitoring

Standard duration is 4-6 weeks of parenteral therapy to prevent treatment failure or relapse. 3, 9 For prosthetic valve endocarditis, extend to 6 weeks or longer. 6

Essential monitoring:

• Repeat blood cultures until sterile 4
• Weekly monitoring of vancomycin and gentamicin levels 2, 4
• Weekly renal function assessment when using aminoglycosides 4
• Repeat echocardiography if new complications develop (new murmur, embolism, persistent fever, heart failure, abscess, AV block) 1

Neurological Complications

After silent embolism or transient ischemic attack, perform cardiac surgery without delay if indicated. 1 Following intracranial hemorrhage, postpone surgery for ≥1 month. 1 Neurosurgery or endovascular therapy is indicated for very large, enlarging, or ruptured intracranial infectious aneurysms. 1

Cardiac Device-Related Infective Endocarditis

Complete hardware removal (device and leads) plus prolonged antibiotic therapy (before and after extraction) is required for definite device-related endocarditis and isolated pocket infections. 1 Percutaneous extraction is recommended even for vegetations >10 mm. 1

Key Clinical Pitfalls

Do not delay empirical antibiotics while awaiting culture results in acutely ill patients—the critical window for treatment initiation directly impacts mortality. 2, 3 Adjust therapy within 48 hours once pathogen identification and susceptibility testing are available. 3

Avoid outpatient parenteral antibiotic therapy (OPAT) in patients with:

• Heart failure 3
• Concerning echocardiographic features 3
• Neurological signs 3
• Renal impairment 3

Consider OPAT only for stable patients with uncomplicated infections (oral streptococci or S. bovis, native valve) after the critical first 2 weeks. 3