August 2025
| American Heart Association (AHA) (MIC ≤0.12 mcg/mL) | European Society of Cardiology (ESC) (MIC ≤0.125 mcg/mL) | |
| Adult | Pediatric | |
| 4-week regimens¶: | 4-week regimens: | 4-week regimens¶Δ: |
| Aqueous penicillin G 12 to 18 million units per 24 hours IV either continuously or in 4 or 6 divided doses or (if penicillin is unavailable) Ampicillin 2 g IV every 4 hours or Ceftriaxone¥ 2 g per 24 hours IV or IM in 1 dose | 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) or (if penicillin is unavailable) Ampicillin 200 to 300 mg/kg per 24 hours IV divided in 4 or 6 divided doses (maximum dose: 12 g per 24 hours) 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) | Aqueous penicillin G¶ 12 to 18 million units per 24 hours IV in 4 or 6 divided doses or continuous infusion or Amoxicillin 100 to 200 mg/kg per 24 hours IV in 4 to 6 divided doses or Ceftriaxone¶¥ 2 g per 24 hours IV or IM in 1 dose |
| Beta-lactam-intolerant patients: Vancomycin◊ 30 mg/kg per 24 hours IV in 2 divided doses | 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) | Beta-lactam-intolerant patients: Vancomycin◊ 30 mg/kg per 24 hours IV in 2 divided doses |
| 2-week regimens‡: | 2-week regimens‡: | 2-week regimensΔ‡: |
| Either Aqueous penicillin G 12 to 18 million units per 24 hours IV either continuously or in 6 divided doses or Ceftriaxone 2 g per 24 hours IV or IM in 1 dose plus Gentamicin†,** 3 mg/kg per 24 hours IV or IM in 1 dose (preferred) or in 3 divided doses | Not recommended for children due to lack of data | Either Aqueous penicillin G 12 to 18 million units per 24 hours IV in 4 to 6 divided doses or continuous infusion or Amoxicillin 100 to 200 mg/kg per 24 hours IV in 4 to 6 divided doses or Ceftriaxone¶¥ 2 g per 24 hours IV or IM in 1 dose plus Gentamicin†,¶¶ 3 mg/kg per 24 hours IV or IM in 1 dose |
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 IM administration is provided as an alternative, IV 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. AHA and ESC guidelines are presented at the top of each column. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) uses MIC threshold ≤0.25 mcg/mL.
¶ Preferred in most patients >65 years or with impairment of cranial nerve VIII or kidney function.
Δ ESC 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.
◊ Vancomycin therapy is only recommended for patients severely allergic to penicillin or cephalosporins. Penicillin desensitization can be attempted in stable patients. In adults, vancomycin is dosed based on actual body weight. The dose should be adjusted for trough concentration of 10 to 15 mcg/mL. Daptomycin is not a substitute for vancomycin for treatment of streptococcal NVE (refer to UpToDate topic on treatment of NVE for further discussion).
§ In infants and children, IV antibiotics are recommended rather than IM agents.
¥ Often favored for patient convenience and ease of administration in outpatient therapy.
‡ For noncomplicated infective endocarditis. Not intended for patients with known cardiac or extracardiac abscess or for creatinine clearance <20 mL/min, impaired 8th nerve function, or infection due to Abiotrophia, Granulicatella spp, or Gemella spp.
† Kidney function and gentamicin serum concentrations should be monitored at least once per week. Gentamicin dose adjusted for peak serum concentrations 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).
** Gentamicin may be given as a single daily dose (3 mg/kg per day; preferred in outpatients) or in 2 to 3 equally divided doses (adjusted to achieve a peak serum level of 3 to 4 mcg/mL; preferred in hospitalized patients when serum concentrations can be followed).
¶¶ Netilmicin (4 to 5 mg/kg/day IV in 1 dose) is an alternative.
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