Version July 2025
| American Heart Association (AHA)¶ | European Society of Cardiology (ESC) | |
| Adult dose | Pediatric dose | Adult dose |
| Strains with intrinsic penicillin resistanceΔ | Strains with intrinsic penicillin resistanceΔ | Strains with intrinsic penicillin resistanceΔ |
| Vancomycin◊ 30 mg/kg per 24 hours IV in 2 divided doses for 6 weeks plus Gentamicin§ 3 mg/kg per 24 hours IV or IM in 3 divided doses for 6 weeks | Vancomycin◊ 40 mg/kg per 24 hours IV (maximum dose: 2 g per 24 hours unless levels are inappropriately low) in 2 or 3 divided doses for 6 weeks plus Gentamicin§ 3 to 6 mg/kg per 24 hours IV in 3 divided doses for 6 weeks¥ | Vancomycin◊ 30 mg/kg per 24 hours IV in 2 divided doses for 6 weeks plus Gentamicin§ 3 mg/kg per 24 hours IV or IM in 1 dose for 2 weeks |
| Beta-lactamase-producing strains | Beta-lactamase-producing strains | Beta-lactamase-producing strains |
| Either Ampicillin-sulbactam‡ 3 g every 6 hours IV for 6 weeks or Vancomycin◊ 30 mg/kg per 24 hours IV in 2 divided doses for 6 weeks plus Gentamicin§ 3 mg/kg per 24 hours IV or IM in 3 divided doses for 6 weeks | Refer to above | Either Ampicillin-sulbactam‡ 12 g per 24 hours (or 300 mg/kg per 24 hours) IV in 4 equally divided doses for 6 weeks or Amoxicillin-clavulanate‡ 200 mg/kg (amoxicillin component) per 24 hours IV in 6 equally divided doses for 6 weeks or Vancomycin◊ 30 mg/kg per 24 hours IV in 2 divided doses for 6 weeks plus Gentamicin§ 3 mg/kg per 24 hours IV or IM in 1 dose for 2 weeks |
AHA: American Heart Association; ESC: European Society of Cardiology; HLAR: high-level aminoglycoside resistance; IM: intramuscularly; IV: intravenously; MIC: minimum inhibitory concentration; PVE: prosthetic valve endocarditis.
* Patients who are unable to tolerate beta-lactams should receive treatment as for infection due to isolates with intrinsic penicillin resistance. Penicillin desensitization should be considered.
¶ Duration of treatment for prosthetic valve or other prosthetic material infective endocarditis is a minimum of 6 weeks.
Δ Intrinsic penicillin resistance defined as penicillin or ampicillin MIC ≥16 mcg/mL; consultation with infectious disease specialist recommended.
◊ Vancomycin therapy is recommended only in the setting of intrinsic penicillin resistance or for patients unable to tolerate beta-lactams (refer to UpToDate text regarding beta-lactam intolerance). Vancomycin dose should be adjusted for serum trough concentration 10 to 20 mcg/mL. In adults, vancomycin is dosed based on actual body weight. The dose may need to be increased beyond 30 mg/kg and frequency may need to be increased to 3 divided doses.
§ Kidney function and gentamicin serum concentrations should be monitored at least once per week. In non-obese and non-underweight adults, aminoglycosides are dosed based on ideal body weight. Gentamicin dosage adjusted for peak serum concentrations 3 to 4 mcg/mL, trough <1 mcg/mL when 2 to 3 divided doses used. When given in a single daily dose, pre-dose (trough) concentrations should be <1 mcg/mL. Per ESC guidelines, post-dose (peak, 1 hour after injection) serum concentrations should be approximately 10 to 12 mcg/mL (per AHA guidelines, there is no role for measuring peak gentamicin concentration following single daily dosing). We favor combination therapy with vancomycin for 6 weeks plus gentamicin for 6 weeks (duration as permitted by kidney function); refer to UpToDate text for alternative options with lower risk of nephrotoxicity.
¥ Regarding gentamicin dosing frequency in children: AHA guidance consists of 2 or 3 divided doses[2]; single daily dosing (per ESC guidance) is also acceptable[3].
‡ If the strain is gentamicin resistant, then >6 weeks of ampicillin-sulbactam or amoxicillin-clavulanate therapy may be needed; refer to local product information for optimal dosing and frequency of intravenous amoxicillin-clavulanate. The strain should be evaluated for HLAR to streptomycin; if the strain also has HLAR to streptomycin or if streptomycin is not available, treatment with non-synergistic therapy carries high risk of treatment failure. Infectious disease consultation is advised; use of daptomycin combined with ceftaroline or ampicillin may be an alternative option.