Empirical Antimicrobial Management of Infective Endocarditis

Community‑Acquired Native Valve Infective Endocarditis

The American Heart Association recommends ampicillin plus (flu)cloxacillin/oxacillin plus gentamicin as the first-line regimen for empirical treatment of community-acquired native valve infective endocarditis 2
For patients with community-acquired native valve IE, the standard empirical regimen is ampicillin 12 g/day IV in 4-6 doses, plus (flu)cloxacillin/oxacillin 12 g/day IV in 4-6 doses, plus gentamicin 3 mg/kg/day IV or IM in 1 dose 2
For penicillin-allergic patients, the European Heart Journal recommends vancomycin 30-60 mg/kg/day IV in 2-3 doses, plus gentamicin 3 mg/kg/day IV or IM in 1 dose 2
For early prosthetic valve endocarditis or healthcare-associated IE, the empirical regimen must cover methicillin-resistant organisms, with vancomycin 30 mg/kg/day IV in 2 doses, plus gentamicin 3 mg/kg/day IV or IM in 1 dose, plus rifampin 900-1200 mg IV or orally in 2-3 divided doses 3, 2

For penicillin-susceptible streptococci, the European Heart Journal recommends penicillin G or ceftriaxone plus gentamicin for 2 weeks, or penicillin G or ceftriaxone alone for 4 weeks 4
For enterococcal endocarditis, the European Heart Journal recommends amoxicillin 200 mg/kg/day IV in 4-6 doses for 6 weeks, plus gentamicin 3 mg/kg/day IV or IM in 1 dose for 2-6 weeks 3, 5
For methicillin-susceptible S. aureus native valve IE, the European Heart Journal recommends nafcillin or oxacillin 12 g/day IV in 4-6 doses for 4-6 weeks 3
For methicillin-resistant S. aureus, the European Heart Journal recommends vancomycin 30 mg/kg/day IV in 2 doses for 6 weeks, with vancomycin trough levels ≥20 mg/L and AUC/MIC >400 recommended 3

For prosthetic valve staphylococcal IE, add rifampin 900 mg/day in 3 doses, plus gentamicin for the first 2 weeks 3
For HACEK group bacteria, the European Heart Journal recommends ceftriaxone 2 g/day IV for 4 weeks (native valve) or 6 weeks (prosthetic valve) 5, 2
For fungal endocarditis, the American Heart Association recommends combined medical and surgical therapy, with amphotericin B-containing product (induction phase), plus mandatory valve replacement, plus lifelong oral azole suppressive therapy 6

The European Heart Journal recommends monitoring renal function and serum gentamicin levels weekly (twice weekly in renal impairment) 3, 5
Target trough levels <1 mg/L and peak levels 10-12 mg/L when using divided dosing 4
The European Heart Journal recommends targeting vancomycin trough levels 10-15 mg/L (some sources recommend ≥20 mg/L for MRSA) 3, 4
Obtain follow-up blood cultures to document clearance of bacteremia 2