Version July 2025
| American Heart Association (AHA) | European Society of Cardiology (ESC) | |
| Adult dose | Pediatric dose | Adult dose |
| Strains with intrinsic penicillin resistance¶ | Strains with intrinsic penicillin resistance¶ | Strains with intrinsic penicillin resistance¶ |
| VancomycinΔ 30 mg/kg per 24 hours IV in 2 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 preference) or in 3 divided doses for 6 weeks (AHA guidance)[1] | VancomycinΔ 40 mg/kg per 24 hours IV (maximum dose: 2 g per 24 hours unless levels are inappropriately low) in 2 or 3 divided doses for 6 weeks plus Gentamicin◊ 3 to 6 mg/kg per 24 hours IV in 3 divided doses for 6 weeks§ | VancomycinΔ 30 mg/kg per 24 hours IV in 2 divided doses for 6 weeks plus Gentamicin◊ 3 mg/kg per 24 hours IV or IM in 1 dose for 2 weeks |
| Inducible beta-lactamase-producing strains¥ | Inducible beta-lactamase-producing strains¥ | Inducible beta-lactamase-producing strains¥ |
| Either Ampicillin-sulbactam¥ 3 g every 6 hours IV for 6 weeks or VancomycinΔ 30 mg/kg per 24 hours IV in 2 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 preference) or in 3 divided doses for 6 weeks (AHA guidance)[1] | Refer to above | Either Ampicillin-sulbactam¥ 12 g per 24 hours (or 300 mg/kg per 24 hours) IV in 4 equally divided doses for 4 to 6 weeks‡ or Amoxicillin-clavulanate¥ 200 mg/kg (amoxicillin component) per 24 hours IV in 6 equally divided doses for 4 to 6 weeks‡ or VancomycinΔ 30 mg/kg per 24 hours IV in 2 divided doses 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 with isolates susceptible to penicillin who are unable to tolerate beta-lactams should receive treatment as for infection due to isolates with intrinsic penicillin resistance.
¶ Intrinsic penicillin resistance defined as penicillin or ampicillin MIC ≥16 mcg/mL; consultation with infectious disease specialist recommended.
Δ Vancomycin therapy is recommended only in the setting of intrinsic penicillin resistance or for patients unable to tolerate beta-lactams (refer to UpToDate text regarding beta-lactam intolerance). Vancomycin dose should be adjusted for serum trough concentration 10 to 20 mcg/mL; some favor trough concentration 15 to 20 mcg/mL. In adults, vancomycin is dosed based on actual body weight. The dose may need to be increased beyond 30 mg/kg and frequency may need to be increased to 3 divided doses.
◊ The 2015 AHA guidance includes a gentamicin duration of 6 weeks; in such cases we shorten the gentamicin component to 2 weeks. Kidney function and gentamicin serum concentrations should be monitored at least once per week. In non-obese and non-underweight adults, aminoglycosides are dosed based on ideal body weight. Gentamicin dosage 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).
§ 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].
¥ Cases of beta-lactamase inducing strains are rare. These are susceptible to ampicillin/sulbactam and vancomycin. If strain is gentamicin resistant, then >6 weeks of ampicillin-sulbactam or amoxicillin-clavulanate therapy may be needed. Refer to local product information for optimal dosing and frequency of intravenous amoxicillin-clavulanate. Strain should be evaluated for HLAR to streptomycin.
‡ Patients with NVE and symptoms <3 months may be treated for 4 weeks; patients with NVE with symptoms >3 months should be treated for at least 6 weeks.