Version July 2025
| American Heart Association (AHA) | European Society of Cardiology*[1] (ESC) | |
| Adult[2] | Pediatric[3] | |
| Methicillin-susceptible strains¶ | Methicillin-susceptible strains | Methicillin-susceptible strains |
| Nafcillin or oxacillin 12 g per 24 hours IV in 4 or 6 divided doses for 6 weeks or CefazolinΔ 6 g per 24 hours IV in 3 divided doses for 6 weeks | Nafcillin or oxacillin 200 mg/kg per 24 hours IV (maximum dose: 12 g per 24 hours) in 4 or 6 divided doses for 4 to 6 weeks or CefazolinΔ 100 mg/kg per 24 hours IV (maximum dose: 6 g per 24 hours) in 3 divided doses for 4 to 6 weeks | Oxacillin or cloxacillin or flucloxacillin 12 g per 24 hours IV in 4 or 6 divided doses for 4 to 6 weeks or CefazolinΔ 6 g per 24 hours IV in 3 divided doses for 4 to 6 weeks or Cefotaxime 6 g per 24 hours in 3 divided doses |
| Beta-lactam-intolerant patients: Daptomycin 10 mg/kg per 24 hours IV once daily for 4 to 6 weeks plus one of the following Ceftaroline 1800 mg/day IV in 3 divided doses for 4 to 6 weeks or Fosfomycin 8 to 12 g/day IV in 4 divided doses for 4 to 6 weeks | ||
| Methicillin-resistant strains | Methicillin-resistant strains◊ | Methicillin-resistant strains |
| Vancomycin§ for 6 weeks | Vancomycin§ 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 | Vancomycin§ 30 to 60 mg/kg per 24 hours IV in 2 or 3 divided doses for 4 to 6 weeks |
| Alternative regimen: Daptomycin ≥8 mg/kg¥ per 24 hours IV once daily for 6 weeks | Alternative regimen: Daptomycin¥‡ 10 mg/kg per 24 hours IV once daily for 4 to 6 weeks plus one of the following Cloxacillin 12 g per 24 hours IV in 6 divided doses for 4 to 6 weeks or Ceftaroline 1800 mg/day IV in 3 divided doses for 4 to 6 weeks or Fosfomycin 8 to 12 g/day IV in 4 divided doses for 4 to 6 weeks | |
AUC: area under the concentration-time curve; ESC: European Society of Cardiology; IM: intramuscularly; IV: intravenously.
* Pediatric doses (should not exceed adult doses): oxacillin, cloxacillin, or flucloxacillin: 200 to 300 mg/kg per 24 hours IV in 4 or 6 divided doses; trimethoprim-sulfamethoxazole (cotrimoxazole) 12 mg/kg trimethoprim component per 24 hours IV in 2 divided doses; clindamycin 40 mg/kg per 24 hours IV in 3 divided doses; vancomycin 40 mg/kg per 24 hours IV in 2 or 3 divided doses; daptomycin 10 mg/kg per 24 hours IV once daily.
¶ Regimens for complicated right-sided and all left-sided infective endocarditis.
Δ Cefazolin may be used in patients with nonsevere penicillin allergy. Cefazolin should be avoided in patients with complicating brain abscess; in such cases, nafcillin is preferred.
◊ Consultation with a pediatric infectious disease specialist is recommended in cases of infection due to methicillin-resistant strains.
§ Per guidelines issued in 2020[4], vancomycin dosing consists of a loading dose: 20 to 35 mg/kg based on actual body weight, rounded to the nearest 250 mg increment, and not exceeding 3000 mg; within this range, we use a higher dose for critically ill patients. The initial maintenance vancomycin dose and interval are determined by nomogram and typically consists of 15 to 20 mg/kg every 8 to 12 hours for most patients with normal kidney function. The subsequent vancomycin dose and interval adjustments are based on AUC-guided (preferred) or trough-guided serum concentration monitoring. Refer to the UpToDate topic on vancomycin dosing for sample nomogram and discussion of AUC-guided and trough-guided vancomycin dosing.
¥ We favor combination therapy with daptomycin in conjunction with a second antimicrobial agent, as recommended by the ESC[1]. Decisions regarding selection and dosing of daptomycin selection should be made in conjunction with infectious disease expertise.
‡ The ESC recommends addition of cloxacillin, ceftaroline, or fosfomycin to daptomycin, to increase antimicrobial activity and avoid emergence of daptomycin resistance.