Version July 2025
| American Heart Association (AHA) | European Society of Cardiology¶ (ESC) (MIC >0.125 and <2 mcg/mL)* | |
| Adult (MIC >0.12 and <0.5 mcg/mL)* | Pediatric (MIC >0.1 and <0.5 mcg/mL)* | |
| Combination therapy: Either Aqueous penicillin G 24 million units per 24 hours IV either continuously or in 4 or 6 divided doses for 4 weeks or Ampicillin 2 g IV every 4 hours for 4 weeks plus GentamicinΔ 3 mg/kg per 24 hours IV or IM in 1 dose for first 2 weeks | Combination therapy: Either Aqueous penicillin G 200,000 to 300,000 units/kg per 24 hours IV in 6 divided doses (maximum dose: 24 million units per 24 hours) for 4 weeks or Ampicillin 200 to 300 mg/kg per 24 hours IV divided in 4 or 6 divided doses (maximum dose: 12 g per 24 hours) for 4 weeks or Ceftriaxone 100 mg/kg per 24 hours IV in 2 divided doses or 80 mg/kg in 1 daily dose (maximum dose: 4 g per 24 hours; if dose is >2 g per 24 hours, use divided dosing every 12 hours) for 4 weeks plus GentamicinΔ 3 to 6 mg/kg per 24 hours IV in 3 divided doses for first 2 weeks | Combination therapy: Either Aqueous penicillin G 24 million units per 24 hours IV in 4 or 6 divided doses or continuous infusion for 4 weeks or Amoxicillin 200 mg/kg per 24 hours IV in 4 or 6 divided doses for 4 weeks or Ceftriaxone 2 g per 24 hours IV or IM in 1 dose for 4 weeks plus GentamicinΔ 3 mg/kg per 24 hours IV or IM in 1 dose for 2 weeks |
| Monotherapy: Ceftriaxone 2 g per 24 hours IV or IM in 1 dose for 4 weeks or Vancomycin◊ 30 mg/kg per 24 hours IV in 2 divided doses for 4 weeks | Beta-lactam-intolerant patients: Vancomycin◊ 40 mg/kg per 24 hours IV in 2 or 3 divided doses (maximum dose: 2 g per 24 hours unless levels are inappropriately low) | Beta-lactam-intolerant patients: Vancomycin◊ 30 mg/kg per 24 hours IV in 2 divided doses for 4 weeks plus GentamicinΔ 3 mg/kg per 24 hours IV or IM in 1 dose for first 2 weeks |
The doses above are intended for patients with normal kidney function. The doses of many of these agents must be adjusted in the setting of kidney function impairment; refer to the individual drug monographs included within UpToDate for renal dosing adjustments.
Wherever intramuscular administration is provided as an alternative, intravenous route is preferred, particularly in infants and children.IM: intramuscularly; IV: intravenously; MIC: minimum inhibitory concentration; NVE: native valve endocarditis.
* MIC thresholds differ between guidelines, as summarized above. Patients with infective endocarditis due to isolates with MICs that exceed these thresholds should receive treatment as for enterococcal infective endocarditis, as summarized in separate tables.
¶ Pediatric doses (should not exceed adult doses): Penicillin G 200,000 units/kg per 24 hours IV in 4 to 6 divided doses; amoxicillin 300 mg/kg per 24 hours IV in 4 to 6 divided doses; ceftriaxone 100 mg/kg per dose IV or IM daily; vancomycin 40 mg/kg per 24 hours IV in 2 or 3 divided doses; gentamicin 3 mg/kg per 24 hours IV or IM in a single daily dose or in 3 divided doses.
Δ Kidney function and gentamicin serum concentrations should be monitored at least once per week. Gentamicin dosage adjusted for peak serum concentration 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).
◊ Vancomycin therapy only recommended for patients allergic to penicillins and cephalosporins; dose adjusted for trough concentration of 10 to 15 mcg/mL. Penicillin desensitization can be attempted in stable patients.