What is the treatment for infective endocarditis?

Treatment of Infective Endocarditis

Treatment of infective endocarditis requires prompt initiation of pathogen-directed antimicrobial therapy for 4-6 weeks combined with early surgical consultation, as approximately 50% of patients will require valve replacement to reduce mortality. 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 avoid culture-negative endocarditis. 2, 1, 3, 4 This is critical—administering antibiotics before cultures makes diagnosis and treatment significantly more difficult. 4

Empirical Antibiotic Therapy

When to Start Empirical Treatment

Start empirical antibiotics immediately after blood cultures are drawn in patients with: 3, 4

• Sepsis or hemodynamic instability
• Acute heart failure
• Severe systemic signs of infection

Do not delay empirical treatment in critically ill patients, but always obtain blood cultures first. 2, 1

Empirical Regimen Selection Based on Clinical Context

For community-acquired native valve endocarditis: 3, 4

• First-line: Ampicillin 12 g/day IV (in 4-6 divided doses) + (flucloxacillin or oxacillin) + gentamicin 3 mg/kg/day IV/IM (single daily dose)
• Penicillin allergy: Vancomycin 30-60 mg/kg/day IV (in 2-3 doses) + gentamicin 3 mg/kg/day IV/IM (single dose)

For prosthetic valve endocarditis or healthcare-associated infection: 3, 4

• Vancomycin 30 mg/kg/day IV (in 2 doses) + gentamicin 3 mg/kg/day IV/IM (single dose) + rifampin 900-1200 mg IV or oral (in 2-3 divided doses)

The choice depends on four key factors: 1, 3

• Previous antibiotic exposure
• Native versus prosthetic valve (and timing of surgery if prosthetic)
• Setting of infection (community vs. nosocomial vs. healthcare-associated)
• Local antibiotic resistance patterns

Pathogen-Specific Treatment

Streptococcal Endocarditis

Use penicillin, ceftriaxone, or vancomycin (for penicillin-allergic patients). 1 Duration is typically 4 weeks for native valve, 6 weeks for prosthetic valve. 5

Enterococcal Endocarditis

Combination therapy is mandatory: ampicillin or penicillin plus gentamicin; use vancomycin for resistant strains. 1 Single-agent therapy fails due to lack of bactericidal activity. 5

Staphylococcal Endocarditis

Native valve: 1

• Methicillin-susceptible: Nafcillin, oxacillin, or cefazolin
• Methicillin-resistant: Vancomycin
• Alternative for right-sided S. aureus endocarditis: Daptomycin 6 mg/kg IV daily is FDA-approved 6

Prosthetic valve: Triple therapy with rifampin + gentamicin + (nafcillin/oxacillin OR vancomycin based on methicillin susceptibility). 1 The addition of rifampin is critical for biofilm penetration on prosthetic material. 1

HACEK Organisms

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

Non-HACEK Gram-Negative Bacteria

This is a surgical emergency. 2 Requires early surgery plus at least 6 weeks of bactericidal combination therapy with beta-lactams and aminoglycosides, sometimes adding quinolones or cotrimoxazole based on susceptibility. 2, 3 In vitro bactericidal testing and antibiotic level monitoring are essential. 2

Fungal Endocarditis

Mortality exceeds 50% even with optimal treatment. 2, 3 Treatment necessitates combined antifungal therapy AND surgical valve replacement—medical therapy alone is inadequate. 2, 1 Most common in prosthetic valves, IV drug users, and immunocompromised patients. 2

Blood Culture-Negative Endocarditis (BCNIE)

Consult infectious disease specialist immediately. 2, 1 Consider specific pathogens: 2

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

Duration and Monitoring of Antimicrobial Therapy

Standard duration is 4-6 weeks of parenteral therapy to prevent treatment failure or relapse. 1, 5 This extended duration is necessary because vegetations have poor antibiotic penetration and harbor high bacterial densities. 5

Essential monitoring includes: 1, 3, 4

• Therapeutic drug monitoring for vancomycin and aminoglycosides (mandatory to prevent nephrotoxicity and ensure efficacy)
• Serial blood cultures to document clearance
• Renal function assessment when using aminoglycosides
• Repeat echocardiography if new complications develop (new murmur, heart failure, persistent fever, embolic events, conduction abnormalities)

Surgical Indications

Approximately 50% of patients require surgical intervention. 1, 4, 7 Early cardiac surgery consultation is mandatory. 1, 4

Absolute indications for surgery: 1

• Heart failure due to severe valve dysfunction (most important prognostic factor)
• Uncontrolled infection (abscess, false aneurysm, fistula, enlarging vegetation despite appropriate antibiotics)
• Prevention of systemic embolism (particularly with large mobile vegetations >10mm)
• Fungal or multidrug-resistant organism infections
• Persistent positive blood cultures after 5-7 days of appropriate antibiotics

Timing matters critically: In patients with uncontrolled infection operated within 10 days, survival is 83%, compared to 10% survival if surgery is delayed 4-6 weeks while attempting medical management. 8 For progressive heart failure, recurrent embolization, or progressive sepsis despite treatment, perform valve replacement within 7 days of starting antibiotics. 8

Periannular abscesses occur in 42-85% of surgical cases and are associated with higher mortality (19% vs 11% without abscess). 9 These patients require surgery in 84-91% of cases versus 36% without abscess. 9

Multidisciplinary Team Approach

Management by an "Endocarditis Team" is essential, including infectious disease specialists, cardiologists, cardiac surgeons, and microbiologists. 1, 4 Complex cases—rare pathogens, BCNIE, multidrug-resistant organisms, or non-HACEK gram-negatives—must be discussed by this team. 2, 1

Outpatient Parenteral Antibiotic Therapy (OPAT)

OPAT is only appropriate for highly selected stable patients with uncomplicated native valve endocarditis caused by oral streptococci or S. bovis after completing the critical first 2 weeks as an inpatient. 1

Absolute contraindications to OPAT: 1

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

Critical Pitfalls to Avoid

Never use daptomycin for pneumonia—it is inactivated by pulmonary surfactant. 6

Daptomycin is not indicated for left-sided endocarditis due to poor outcomes in clinical trials, though it is FDA-approved for right-sided S. aureus endocarditis. 6

Do not administer daptomycin as a 2-minute IV push in pediatric patients—use 30-minute infusion (ages 7-17) or 60-minute infusion (ages 1-6). 6

Avoid monotherapy for enterococcal endocarditis—it lacks bactericidal activity and leads to treatment failure. 1, 5

Do not delay surgery in fungal endocarditis or non-HACEK gram-negative infections—medical therapy alone is inadequate. 2, 3