August 2025
| American Heart Association (AHA) (MIC ≥0.50 mcg/mL) | European Society of Cardiology (ESC) (MIC ≥2 mcg/mL) | |
| Adult | Pediatric | Adult |
| Combination therapy: Either Aqueous penicillin G 24 million units per 24 hours IV either continuously or in 4 or 6 divided doses for 6 weeks or Ampicillin 2 g IV every 4 hours for 6 weeks or Ceftriaxone¶ 2 g/24 hours IV in 1 dose for 6 weeks plus GentamicinΔ◊ 3 mg/kg per 24 hours IV or IM in 1 dose for 6 weeks | Combination therapy: Either 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 or 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 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) for 6 weeks plus GentamicinΔ 3 to 6 mg/kg per 24 hours IV in 3 divided doses for 6 weeks§ | Combination therapy: Either Aqueous penicillin G 24 million units per 24 hours IV in 4 or 6 divided doses or continuously for 6 weeks or Amoxicillin 12 g per 24 hours IV in 6 divided doses for 6 weeks or Ceftriaxone¶ 2 g per 24 hours IV in 1 dose for 6 weeks plus GentamicinΔ◊ 3 mg/kg per 24 hours IV or IM in 1 dose for 2 weeks |
| Monotherapy/beta-lactam-intolerant patients¥: Vancomycin‡ 30 mg/kg per 24 hours IV in 2 divided doses for 6 weeks | 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 unless levels are inappropriately low) for 6 weeks | Beta-lactam-intolerant patients: Vancomycin‡ 30 mg/kg per 24 hours IV in 2 doses for 6 weeks plus GentamicinΔ◊ 3 mg/kg per 24 hours IV or IM in 1 dose for 2 weeks |
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.
AHA: American Heart Association; ESC: European Society of Cardiology; IM: intramuscularly; IV: intravenously; MIC: minimum inhibitory concentration; PVE: prosthetic valve endocarditis.
* Refer to the UpToDate treatment topic for approach to treatment of PVE due to Abiotrophia defectiva, Granulicatella spp, and Gemella spp.
¶ Alternative in patients with nonsevere penicillin allergy; preferred for outpatient therapy.
Δ In adults, aminoglycosides are dosed based on ideal body weight. Kidney function and serum gentamicin concentrations should be monitored at least once per week. When given in 3 divided doses (per AHA pediatric guidelines[1]), pre-dose (trough) concentrations should be <1 mcg/mL and post-dose (peak, 1 hour after infection) should be between 3 and 4 mcg/mL. When given in a single daily dose (per AHA adult guidelines and ESC guidelines[2,3]), 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). Refer to the UpToDate topic on antimicrobial therapy of PVE for duration of gentamicin therapy based on penicillin susceptibility or infecting species.
◊ Our approach to gentamicin dosing in adults differs from that suggested by the AHA and ESC. The duration of gentamicin depends on the degree of penicillin resistance. For fully penicillin-resistant strains (MIC ≥0.5 mcg/mL and particularly those with MIC ≥2 mcg/mL), we administer gentamicin for 6 weeks. Refer to the UpToDate topic on treatment of PVE for further discussion.
§ Regarding gentamicin dosing frequency in children: AHA guidance consists of 2 or 3 divided doses[1]; single daily dosing (per ESC guidance) is also acceptable[3].
¥ For fully penicillin-resistant strains (per AHA, MIC ≥0.5 mcg/mL), vancomycin monotherapy can be used; in general we do not give gentamicin with vancomycin because of the increased risk of nephrotoxicity with co-administration of these agents. For fully resistant strains in beta-lactam intolerant patients, another approach is desensitization followed by beta lactam-gentamicin combination therapy. For strains with MIC >2.0 mcg/mL, we favor beta lactam-gentamicin combination therapy unless there are contraindications to gentamicin or the isolate demonstrates high-level gentamicin resistance.
‡ In general, vancomycin therapy is recommended for patients severely allergic to penicillin and cephalosporins. Penicillin desensitization can be attempted in stable patients. For patients in whom aminogylcosides are contraindicated, vancomycin monotherapy can be used. 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 PVE; refer to UpToDate topic on treatment of PVE for further discussion.
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