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 | Aminoglycoside combination regimenΔ |
| Either Ampicillin 2 g IV every 4 hours for 6 weeks or Aqueous penicillin G 18 to 30 million units per 24 hours continuously or in 6 divided doses for 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 | Either Amoxicillin 200 mg/kg/day in 4 to 6 doses for 4 to 6 weeks◊ or Ampicillin 12 g per day (200 mg/kg per day) in 4 or 6 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 |
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 PVE due to an enterococcal strain resistant to penicillin and susceptible to vancomycin and aminoglycosides.
¶ In general, the ampicillin-ceftriaxone combination regimen is preferred over the streptomycin 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 Enterococcus 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.
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).
◊ 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. The risk of irreversible cranial nerve VIII toxicity is high with 6 weeks of streptomycin. Streptomycin combination therapy should not be used in patients who have or develop creatinine clearance <50 mL/min, or who have cranial nerve VIII or visual impairment. Cranial nerve VIII function should be monitored at least weekly during therapy. Alternative considerations, including shortening the streptomycin course or completion of treatment with the beta-lactam combination regimen, should be considered.