What is the treatment for endocarditis?

Treatment of Infective Endocarditis

Infective endocarditis requires immediate bactericidal antibiotic therapy for 4-6 weeks (native valve) or at least 6 weeks (prosthetic valve), with approximately 50% of patients ultimately requiring surgical intervention. 1, 2, 3

Immediate Initial Steps

Obtain three sets of blood cultures at 30-minute intervals before starting antibiotics, then begin empirical therapy immediately without waiting for culture results. 1, 2, 3

• Blood cultures should be drawn at 30-minute intervals to maximize pathogen identification 1, 2
• Do not delay antibiotic initiation in acutely ill patients after cultures are obtained 2, 3
• Consult with an Endocarditis Team (infectious disease specialist, cardiologist, cardiac surgeon, microbiologist) early in management 1, 2, 3

Empirical Antibiotic Regimens

For Native Valve Endocarditis (NVE)

Start ampicillin 12 g/day IV in 4-6 divided doses PLUS (flu)cloxacillin/oxacillin 12 g/day IV in 4-6 divided doses PLUS gentamicin 3 mg/kg/day IV in a single daily dose. 2, 3

• This regimen covers staphylococci, streptococci, and enterococci 2
• Adjust based on local epidemiology and resistance patterns 1, 2

For Prosthetic Valve Endocarditis (PVE)

Start vancomycin 30 mg/kg/day IV in 2 divided doses PLUS gentamicin 3 mg/kg/day IV in 1 dose PLUS rifampin 900-1200 mg/day IV or oral in 2-3 divided doses. 2, 3

• This covers methicillin-resistant staphylococci and biofilm-associated organisms 2, 3
• Rifampin should only be added after 3-5 days of effective therapy once bacteremia has cleared to avoid antagonism against planktonic bacteria 1

Pathogen-Specific Definitive Therapy

Methicillin-Susceptible Staphylococcus aureus (MSSA)

Use (flu)cloxacillin or oxacillin 12 g/day IV in 4-6 divided doses for 4-6 weeks WITHOUT adding gentamicin. 3

• Do not add aminoglycosides to MSSA native valve endocarditis—they provide no clinical benefit and increase nephrotoxicity 3
• Vancomycin is indicated only for penicillin-allergic patients or methicillin-resistant strains 4

Methicillin-Resistant Staphylococcus aureus (MRSA)

Use vancomycin 30 mg/kg/day IV in 2 divided doses for at least 6 weeks with therapeutic drug monitoring. 2, 3, 4

• Vancomycin is effective for staphylococcal endocarditis when used at appropriate doses 4
• Monitor vancomycin trough levels to ensure therapeutic concentrations 2

Streptococcal Endocarditis (Penicillin-Susceptible)

Use penicillin G or ceftriaxone for 4 weeks in native valve endocarditis or 6 weeks in prosthetic valve endocarditis. 1, 2

• Highly susceptible streptococci can be treated with penicillin alone for 4 weeks 1
• Vancomycin is reserved for penicillin-allergic patients 2

Enterococcal Endocarditis

Use 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. 2, 3

• Synergistic bactericidal combination is essential for enterococci 3
• Vancomycin 30 mg/kg/day IV plus gentamicin for 6 weeks is required for resistant strains 1, 2
• Vancomycin-based regimens require longer duration (6 weeks) compared to ampicillin-based regimens (4-6 weeks) 1

HACEK Organisms

Use ceftriaxone 2 g/24 hours IV for 4 weeks in native valve endocarditis or 6 weeks in prosthetic valve endocarditis. 1, 2

Non-HACEK Gram-Negative Bacteria

Use early surgery PLUS long-term therapy (at least 6 weeks) with bactericidal combinations of beta-lactams and aminoglycosides. 1, 2

• These rare and severe infections require Endocarditis Team discussion 1
• Consider adding quinolones or cotrimoxazole based on susceptibility 1

Fungal Endocarditis

Use combined antifungal therapy PLUS mandatory surgical valve replacement. 1, 2, 3

• Mortality exceeds 50% despite aggressive treatment 1, 2
• Medical therapy alone is inadequate 1, 3

Blood Culture-Negative Endocarditis (BCNIE)

For subacute presentation with prior antibiotic use: ampicillin-sulbactam 3 g IV every 6 hours PLUS gentamicin 1 mg/kg IV every 8 hours. 2, 3

• Consider atypical organisms: Brucella (doxycycline 200 mg/24h + cotrimoxazole 960 mg/12h + rifampin 300-600 mg/24h for 3-6 months), Coxiella burnetii (doxycycline 200 mg/24h + hydroxychloroquine 200-600 mg/24h for ≥18 months), or Bartonella (doxycycline 100 mg/12h for 4 weeks + gentamicin 3 mg/24h for 2 weeks) 1, 5
• Mandatory infectious disease specialist consultation for all BCNIE cases 1, 2, 3

Duration of Antibiotic Therapy

Native valve endocarditis: 4 weeks for most pathogens (streptococci, MSSA), 4-6 weeks for enterococci and culture-negative cases. 1, 2

Prosthetic valve endocarditis: Minimum 6 weeks for all pathogens, regardless of organism. 1, 2, 3

• Duration is calculated from the first day of effective antibiotic therapy (when blood cultures become negative), not from the day of surgery 1
• If valve replacement occurs during antibiotic therapy for native valve endocarditis, continue the native valve regimen postoperatively unless valve cultures are positive 1
• Start a new full course only if valve cultures at surgery are positive 1

Aminoglycoside Use: Critical Considerations

Limit aminoglycosides to a maximum of 2 weeks and use once-daily dosing to reduce nephrotoxicity. 3

• Aminoglycosides provide synergy with cell-wall inhibitors for enterococci and some streptococci 1
• Do NOT add aminoglycosides to MSSA native valve endocarditis—no clinical benefit with increased toxicity 3
• Monitor renal function closely when aminoglycosides are used 2, 3
• Therapeutic drug monitoring for gentamicin is essential 2, 3

Monitoring Treatment Response

Persistent bacteremia at 48-72 hours after appropriate therapy indicates lack of infection control and predicts in-hospital mortality. 1

• Staphylococcus aureus bacteremia may persist 3-5 days with beta-lactams or 5-10 days with vancomycin 1
• Persistent infection at day 7 is a better prognostic indicator than blood culture status at 48-72 hours 6
• Remove central venous catheters in catheter-associated S. aureus endocarditis to achieve control 1
• Follow-up blood cultures, clinical assessment, and monitoring of renal function are essential 2, 3

Surgical Indications

Approximately 50% of endocarditis patients require surgical intervention, which should be considered early in consultation with cardiac surgery. 5, 2, 3

Absolute Indications for Surgery:

• Heart failure due to severe valve dysfunction 5, 2
• Uncontrolled infection with abscess formation, false aneurysm, or fistula 2
• Persistent positive blood cultures despite appropriate antibiotic therapy for 48-72 hours 1, 5, 2
• Fungal or multiresistant organism infections 2, 3
• Prevention of systemic embolism with large vegetations (≥10 mm) 5, 2
• Most cases of prosthetic valve endocarditis 2, 3
• Staphylococcus aureus prosthetic valve endocarditis (surgery maximizes outcomes) 3

Outpatient Parenteral Antibiotic Therapy (OPAT)

Consider OPAT only after initial hospital stabilization (first 2 weeks) in highly selected patients with uncomplicated native valve endocarditis caused by oral streptococci or S. bovis. 1, 2

Requirements for OPAT:

• Patient must be hemodynamically stable and afebrile 1, 2
• Negative blood cultures documented 1, 2
• No heart failure, concerning echocardiographic features, neurological signs, or renal impairment 2
• Reliable patient/family adherence to medical plan 1
• Frequent home monitoring by home health nurse 1
• Prompt access (minutes to hours) to medical and surgical care if complications develop 1

Contraindications to OPAT:

• Heart failure 2
• Concerning echocardiographic features (large vegetations, abscess) 2
• Neurological complications 2
• Renal impairment 2
• High-risk pathogens (S. aureus, enterococci, fungi) 2

Critical Pitfalls to Avoid

Do not use bacteriostatic antibiotics—bactericidal therapy is mandatory because host defenses contribute little to microbial eradication. 1, 7

Do not add rifampin to prosthetic valve endocarditis regimens until after 3-5 days of effective therapy and bacteremia clearance to avoid antagonism. 1

Do not use trimethoprim alone for Brucella endocarditis—cotrimoxazole (trimethoprim-sulfamethoxazole combination) is required. 5

Do not add aminoglycosides to MSSA native valve endocarditis—this increases nephrotoxicity without clinical benefit. 3

Do not delay surgical consultation in high-risk cases—early referral to a center with cardiac surgery and an Endocarditis Team improves outcomes. 1, 2

Do not treat fungal endocarditis with antifungals alone—surgical valve replacement is mandatory. 1, 2, 3