Version July 2025
| American Heart Association (AHA) | European Society of Cardiology (ESC) | |
| Adult dose | Pediatric dose | Adult dose |
| 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 to 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/day in 4 to 6 doses for 6 weeks |
| Aminoglycoside combination regimenΔ | Aminoglycoside combination regimenΔ | |
| Either Ampicillin 2 g IV every 4 hours for 4 to 6 weeks◊ or Aqueous penicillin G 18 to 30 million units per 24 hours continuously or in 6 divided doses for 4 to 6 weeks◊ plus Streptomycin§ 15 mg/kg per 24 hours IV or IM in 2 divided doses for 4 to 6 weeks◊ | Consultation with a pediatric infectious disease expert is recommended in all cases of enterococcal infective endocarditis | |
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.
¶ 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 bactericidally synergistic against Enterococcus faecium. This regimen is reasonable for patients with normal kidney function (and preferred for patients with impaired kidney function), abnormal cranial nerve VIII function, and generally in lieu of combination therapy with streptomycin.
Δ For treatment of infection due to isolates that are gentamicin resistant and streptomycin susceptible (growth inhibited by 1000 mcg/mL) in patients with creatinine clearance >50 mL/minute. Although this regimen was used effectively before gentamicin was established as the preferred aminoglycoside, AHA 2015 guidelines discourage its use. This is because of general lack of physician familiarity with streptomycin, supply shortages, lack of readily available laboratory testing for serum concentration monitoring, and cranial nerve VIII toxicity (refer to UpToDate text).
◊ Patients with NVE and symptoms <3 months may be treated for 4 weeks; patients NVE with symptoms ≥3 months should be treated for at least 6 weeks.
§ In adults, streptomycin is dosed based on ideal body weight. Dose should be adjusted to obtain serum peak concentration of 20 to 35 mcg/mL and a trough concentration of <10 mcg/mL.