What is the empiric treatment for an adult with suspected bacterial (infective) endocarditis, including native‑valve and prosthetic‑valve disease?

Empiric Treatment for Bacterial Endocarditis

For community-acquired native valve endocarditis or late prosthetic valve endocarditis (≥12 months post-surgery), start 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 once daily to cover staphylococci, streptococci, and enterococci. 1

Native Valve Endocarditis (Community-Acquired)

Acute Presentation (Days)

• Primary regimen: 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 once daily 1
• This triple-drug combination provides coverage for S. aureus, β-hemolytic streptococci, enterococci, and aerobic Gram-negative bacilli 1
• For penicillin-allergic patients: Vancomycin 30–60 mg/kg/day IV in 2–3 doses PLUS gentamicin 3 mg/kg/day IV/IM once daily 1

Subacute Presentation (Weeks)

• Same regimen as acute: Ampicillin PLUS (flu)cloxacillin/oxacillin PLUS gentamicin 1
• This covers S. aureus, viridans group streptococci (VGS), HACEK organisms, and enterococci 1
• The European Society of Cardiology emphasizes that this regimen should cover staphylococci, streptococci, and enterococci in native valve and late prosthetic valve cases 1

Prosthetic Valve Endocarditis

Early PVE (<12 Months Post-Surgery) or Healthcare-Associated Endocarditis

• Primary regimen: Vancomycin 30 mg/kg/day IV in 2 doses PLUS gentamicin 3 mg/kg/day IV/IM once daily PLUS rifampin 900–1200 mg IV or orally in 2–3 divided doses 1
• Critical timing: Start rifampin 3–5 days after vancomycin and gentamicin have been initiated 1
• This regimen covers methicillin-resistant staphylococci (including MRSA), enterococci, and non-HACEK Gram-negative pathogens 1
• In healthcare-associated native valve endocarditis with MRSA prevalence >5%, some experts recommend combining cloxacillin PLUS vancomycin until final S. aureus identification 1

Late PVE (≥12 Months Post-Surgery)

• Treat as native valve endocarditis: Ampicillin PLUS (flu)cloxacillin/oxacillin PLUS gentamicin 1
• The American Heart Association notes that late PVE is more likely caused by staphylococci, VGS, and enterococci—similar to native valve endocarditis 1

Critical Monitoring and Adjustments

Aminoglycoside Monitoring

• Gentamicin levels: Check weekly; target peak 3–4 µg/mL (or 10–12 mg/L for once-daily dosing) and trough <1 µg/mL 1, 2
• Renal function: Monitor twice weekly, especially in patients with baseline renal impairment 3
• Avoid gentamicin or adjust dose in patients with creatinine clearance <50 mL/min 4, 3

Vancomycin Monitoring

• Target trough levels: 10–15 mg/L for streptococcal IE; 15–20 mg/L for staphylococcal IE 2, 3
• Requires significant dose adjustment and therapeutic drug monitoring in renal impairment 3

Transition to Pathogen-Specific Therapy

• Obtain three sets of blood cultures at 30-minute intervals before initiating antibiotics 3
• Once the pathogen is identified (usually within 48 hours), immediately switch from empiric to pathogen-specific therapy based on antimicrobial susceptibility patterns 1
• Mandatory infectious disease consultation is recommended for all cases of blood culture-negative endocarditis and for optimizing therapy 1, 4

Common Pitfalls to Avoid

• Never use rifampin as monotherapy due to rapid resistance development 3
• Do not add gentamicin to β-lactam therapy for methicillin-susceptible S. aureus (MSSA) native valve endocarditis once the pathogen is identified 2
• Do not add gentamicin or rifampin to vancomycin or daptomycin for MRSA native valve endocarditis once the pathogen is identified 2
• Avoid streptomycin in patients with creatinine clearance <50 mL/min 4, 3
• If initial blood cultures remain negative and there is no clinical response, consider extending antibiotic spectrum to cover blood culture-negative pathogens (add doxycycline or quinolones) and consider surgery for molecular diagnosis 1

Duration of Empiric Therapy

• Continue empiric therapy until pathogen identification (typically 48 hours) 1
• Once switched to pathogen-specific therapy, most native valve cases require 4 weeks total treatment 5
• Prosthetic valve endocarditis requires 6 weeks total treatment 5