What are the standard adult antibiotic regimens for infective endocarditis, including organism‑specific recommendations for native‑valve and prosthetic‑valve infections?

Infective Endocarditis Antibiotic Guidelines

For native valve endocarditis caused by penicillin-susceptible viridans streptococci (MIC ≤0.12 μg/mL), treat with penicillin G 12-18 million units/day IV for 4 weeks, or combine it with gentamicin 3 mg/kg/day for a shortened 2-week course; for prosthetic valve infections, extend all regimens to 6 weeks and add gentamicin for the first 2 weeks. 1

Native Valve Endocarditis (NVE)

Viridans Streptococci & Streptococcus gallolyticus (bovis)

Penicillin-susceptible strains (MIC ≤0.12 μg/mL):

• Standard 4-week regimen: Penicillin G 12-18 million units/day IV in 4-6 divided doses OR ceftriaxone 2 g/day IV/IM once daily for 4 weeks 1
• Shortened 2-week regimen: Same beta-lactam PLUS gentamicin 3 mg/kg/day IV/IM once daily for 2 weeks (only for uncomplicated NVE with normal renal function) 1
• Penicillin allergy: Vancomycin 30 mg/kg/day IV in 2 divided doses for 4 weeks (target trough 10-15 mg/L) 1

Relatively resistant strains (MIC 0.12-0.5 μg/mL):

• Penicillin G 24 million units/day IV OR ceftriaxone 2 g/day IV for 4 weeks PLUS gentamicin 3 mg/kg/day for the first 2 weeks 1
• For penicillin allergy: Vancomycin 30 mg/kg/day IV for 4 weeks PLUS gentamicin 3 mg/kg/day for 2 weeks 1

Highly resistant strains (MIC >0.5 μg/mL):

• Treat as enterococcal endocarditis with ampicillin or penicillin PLUS gentamicin for 4-6 weeks 1

Staphylococcus aureus

Methicillin-susceptible (MSSA):

• Nafcillin or oxacillin 12 g/day IV in 6 divided doses (2 g every 4 hours) for 4-6 weeks 2, 3
• Alternative: Cefazolin 2 g IV every 8 hours for 4-6 weeks (for non-immediate penicillin allergy) 2
• Do NOT add gentamicin for native valve MSSA endocarditis 1

Methicillin-resistant (MRSA):

• Vancomycin 30-60 mg/kg/day IV in 2-3 divided doses for 4-6 weeks (target trough 15-20 mg/L) 2
• Alternative: Daptomycin 6 mg/kg/day IV once daily for 4-6 weeks; consider 8-10 mg/kg/day for complicated cases or vancomycin MIC >1 mg/L 1, 2
• Do NOT add gentamicin or rifampin for native valve MRSA endocarditis 1

Enterococci

Penicillin-susceptible, gentamicin-susceptible:

• Ampicillin 2 g IV every 4 hours (or penicillin G 18-30 million units/day) PLUS gentamicin 3 mg/kg/day IV/IM in divided doses for 4-6 weeks 2
• Vancomycin 30 mg/kg/day IV in 2 divided doses PLUS gentamicin 3 mg/kg/day for 6 weeks (if penicillin-allergic) 2

High-level aminoglycoside resistance:

• Double beta-lactam: Ampicillin 2 g IV every 4 hours PLUS ceftriaxone 2 g IV every 12 hours for 6 weeks 2

HACEK Organisms

• Ceftriaxone 2 g/day IV/IM once daily for 4 weeks 1
• Alternative: Ampicillin-sulbactam 12 g/day IV in 4 divided doses for 4 weeks 1

Prosthetic Valve Endocarditis (PVE)

Viridans Streptococci & S. gallolyticus

Penicillin-susceptible (MIC ≤0.12 μg/mL):

• Penicillin G 24 million units/day IV OR ceftriaxone 2 g/day IV for 6 weeks PLUS gentamicin 3 mg/kg/day for the first 2 weeks 1, 4
• Vancomycin 30 mg/kg/day IV for 6 weeks PLUS gentamicin 3 mg/kg/day for 2 weeks (if penicillin-allergic) 1, 4

Reduced susceptibility (MIC >0.12 μg/mL):

• Same beta-lactam for 6 weeks PLUS gentamicin 3 mg/kg/day for the full 6 weeks 1, 4

Renal impairment (CrCl <30 mL/min):

• Omit gentamicin; use beta-lactam monotherapy for 6 weeks 4

Staphylococcal PVE

Methicillin-susceptible:

• Nafcillin or oxacillin 12 g/day IV in 6 divided doses PLUS rifampin 900 mg/day IV/PO in 3 divided doses for ≥6 weeks PLUS gentamicin 3 mg/kg/day IV/IM in 2-3 divided doses for the first 2 weeks 2, 5

Methicillin-resistant (including coagulase-negative staphylococci):

• Vancomycin 30 mg/kg/day IV in 2 divided doses PLUS rifampin 900 mg/day IV/PO in 3 divided doses for ≥6 weeks PLUS gentamicin 3 mg/kg/day for the first 2 weeks 2, 5
• If gentamicin-resistant but fluoroquinolone-susceptible, substitute a fluoroquinolone for gentamicin 5

Enterococcal PVE

• Ampicillin 2 g IV every 4 hours PLUS gentamicin 3 mg/kg/day for 6 weeks 5
• Test for high-level aminoglycoside resistance; if present, use double beta-lactam regimen for 6 weeks 5

HACEK Organisms (PVE)

• Ceftriaxone 2 g/day IV for 6 weeks 1

Critical Monitoring & Pitfalls

Gentamicin monitoring:

• Check weekly serum levels: target peak 3-4 μg/mL (10-12 mg/L for once-daily dosing), trough <1 mg/L 1
• Monitor renal function and assess for ototoxicity weekly 4
• Avoid gentamicin if CrCl <30 mL/min 4

Vancomycin monitoring:

• Target trough 10-15 mg/L for streptococcal IE, 15-20 mg/L for staphylococcal IE 1, 2

Duration of therapy:

• Count from the first day blood cultures become negative, not from treatment initiation 5
• If valve replacement occurs during therapy, restart the full PVE regimen postoperatively 5
• If resected valve tissue is culture-positive, give a full postoperative course 5

Common errors to avoid:

• Never use gentamicin monotherapy or short-course beta-lactam for enterococcal IE—synergistic combination is mandatory 2, 5
• Do not add gentamicin or rifampin to vancomycin for native valve staphylococcal IE—no proven benefit and increased toxicity 1
• Do not delay surgical consultation for S. aureus PVE, fungal IE, or heart failure—surgery is often lifesaving 5
• Assume coagulase-negative staphylococci are methicillin-resistant in early PVE (<12 months post-surgery) unless proven otherwise 5