Version July 2025
| American Heart Association (AHA) | European Society of Cardiology (ESC) | |
| Adult dose | Pediatric dose¶ | Adult doseΔ |
| Beta-lactam combination regimen◊§ | Beta-lactam combination regimen◊§ | Beta-lactam combination regimen§ |
| Ceftriaxone 2 g IV every 12 hours for 6 weeks plus Ampicillin 2 g IV every 4 hours for 6 weeks | 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 6 weeks plus 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 6 weeks | Ceftriaxone 2 g IV every 12 hours for 6 weeks plus one of the following Ampicillin 12 g per 24 hours (200 mg/kg per 24 hours) IV in 4 or 6 divided doses for 6 weeks or Amoxicillin 200 mg/kg per 24 hours IV in 4 or 6 divided doses for 6 weeks |
| Aminoglycoside combination regimen¥ | Aminoglycoside combination regimen¥ | Aminoglycoside combination regimen |
| Either Aqueous penicillin G 18 to 30 million units per 24 hours IV continuously or in 6 divided doses for 4 to 6 weeks‡ or Ampicillin 2 g IV every 4 hours for 4 to 6 weeks‡ plus Gentamicin† 3 mg/kg per 24 hours IV or IM in a single daily dose for 2 weeks (UpToDate approach) or in 3 divided doses for 4 to 6 weeks (AHA guidance)‡ | 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 to 6 weeks‡ or Ampicillin (dosing as above) for 4 to 6 weeks‡ plus Gentamicin† 3 to 6 mg/kg per 24 hours IV in 2 or 3 divided doses for 4 to 6 weeks‡,** | Either Amoxicillin 200 mg/kg per 24 hours IV in 4 or 6 divided doses for 6 weeks or Ampicillin (dosing as above) 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; NVE: native valve endocarditis.
* Patients unable to tolerate beta-lactams should receive treatment as for infection due to isolates with intrinsic penicillin resistance. Refer to UpToDate table on treatment regimens for native or prosthetic valve endocarditis due to an enterococcal strain resistant to penicillin and susceptible to vancomycin and aminoglycosides.
¶ Consultation with an infectious disease specialist is recommended for pediatric patients with enterococcal endocarditis.
Δ Pediatric doses (should not exceed adult doses): amoxicillin 200 mg/kg per 24 hours IV in 4 to 6 divided doses; ampicillin 300 mg/kg per 24 hours IV in 4 or 6 divided doses; ceftriaxone 100 mg/kg per 24 hours IV or IM in 2 divided doses; gentamicin 3 mg/kg per 24 hours IV or IM in 3 divided doses; vancomycin 40 mg/kg per 24 hours IV in 2 or 3 divided doses.
◊ Recommended for patients with creatinine clearance ≤50 mL/min (either at baseline or while on therapy with aminoglycoside-containing regimen).
§ The beta-lactam combination regimen is active against Enterococcus faecalis strains with and without HLAR and is the combination of choice in patients with HLAR E. faecalis endocarditis; it is not active against E. faecium. This regimen is reasonable for patients with normal or impaired kidney function, abnormal cranial nerve VIII function, or if the laboratory is unable to provide rapid results of aminoglycoside serum concentration.
¥ Recommended for patients with baseline creatinine clearance >50 mL/min.
‡ According to the 2015 AHA guidance[1], patients with NVE and symptoms <3 months may be treated with gentamicin for 4 weeks; patients NVE with symptoms ≥3 months should be treated for at least 6 weeks. For adults with aminoglycoside-susceptible isolates, we shorten the gentamicin component to 2 weeks when used in combination with a beta-lactam, particularly with emergence of nephrotoxicity (refer to UpToDate text).
† Kidney function and gentamicin serum concentrations should be monitored at least once per week. In adults, aminoglycosides are dosed based on ideal body weight. Gentamicin dosage adjusted for peak serum concentrations are 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).
** 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].