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 Ampicillin 2 g IV every 4 hours for 6 weeks or Aqueous penicillin G 18 to 30 million units per 24 hours IV continuously or in 6 divided doses for 6 weeks plus Gentamicin¥ 3 mg/kg per 24 hours IV or IM in a single daily dose for 2 weeks (UpToDate approach, refer to topic text) or in 3 divided doses for 6 weeks (AHA approach)[1] | Either Ampicillin (dosing as above) for 6 weeks or 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 6 weeks plus Gentamicin¥ 3 to 6 mg/kg per 24 hours IV in 2 or 3 divided doses for 6 weeks‡ | Either Ampicillin (dosing as above) for 6 weeks or Amoxicillin 200 mg/kg per 24 hours IV in 4 or 6 divided doses for 6 weeks plus Gentamicin¥ 3 mg/kg per 24 hours IV or IM in 1 dose for 2 weeks |
HLAR: high-level aminoglycoside resistance; IM: intramuscularly; IV: intravenously; PVE: prosthetic 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 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.
◊ In general, the ampicillin-ceftriaxone combination regimen is preferred over the penicillin/ampicillin plus gentamicin combination regimen. The beta-lactam combination regimen is active against Enterococcus faecalis strains (with and without HLAR) and is the regimen of choice for patients with HLAR E. faecalis endocarditis. However, it is not active against Enterococcus faecium; data for other non-faecalis species are limited. The beta-combination regimen may be used 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.
§ Ampicillin (or amoxicillin) is preferred over aqueous penicillin G given better enterococcal activity. The aminoglycoside combination regimen is not recommended for patients with creatinine clearance <50 mL/min.
¥ The 2015 AHA guidance includes a duration of 6 weeks for adults treated with the combination regimen of penicillin or ampicillin plus gentamicin. In such cases, we shorten the gentamicin component to 2 weeks, particularly with emergence of nephrotoxicity (refer to UpToDate text). Kidney function and gentamicin serum concentrations should be monitored at least once weekly. 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].