Version July 2025
| American Heart Association (AHA) | European Society of Cardiology (ESC) | |
| Adult | Pediatric* | Adult |
| Methicillin-susceptible strains | Methicillin-susceptible strains | Methicillin-susceptible strains |
| One of the following¶: Either Nafcillin or oxacillinΔ 12 g per 24 hours IV in 6 divided doses for ≥6 weeks or Cefazolin◊ 6 g per 24 hours IV in 3 divided doses for ≥6 weeks plus Rifampin§ 900 mg per 24 hours IV or orally in 3 divided doses for ≥6 weeks plus Gentamicin¥‡ 3 mg/kg per 24 hours IV or IM in 2 or 3 divided doses for 2 weeks | One of the following¶: Either Nafcillin or oxacillin 200 mg/kg per 24 hours IV (maximum dose: 12 g per 24 hours) in 4 or 6 divided doses for ≥6 weeks or Cefazolin◊ 100 mg/kg per 24 hours IV (maximum dose: 6 g per 24 hours) in 3 divided doses for ≥6 weeks plus Rifampin§ 20 mg/kg per 24 hours IV (maximum dose: 900 mg per 24 hours) in 3 divided doses for ≥6 weeks plus Gentamicin¥‡ 3 to 6 mg/kg per 24 hours IV or IM in 3 divided doses for first 2 weeks† | One of the following¶: Either Oxacillin or cloxacillin or flucloxacillin 12 g per 24 hours IV in 4 or 6 divided doses for ≥6 weeks or Cefazolin◊ 6 g per 24 hours IV in 3 divided doses for ≥6 weeks plus Rifampin§ 900 mg per 24 hours IV or orally in 3 divided doses for ≥6 weeks plus Gentamicin¥‡ 3 mg/kg per 24 hours IV or IM in 1 (preferred) or 2 doses for the first 2 weeks |
| Beta-lactam-intolerant patients: Daptomycin** 10 mg/kg per 24 hours IV once daily for ≥6 weeks plus Rifampin§ 900 mg per 24 hours IV or orally in 3 divided doses for ≥6 weeks plus Gentamicin¥‡ 3 mg/kg per 24 hours IV or IM in 1 (preferred) or 2 doses for the first 2 weeks | ||
| Methicillin-resistant strains** | Methicillin-resistant strains | Methicillin-resistant strains |
| Vancomycin**,¶¶ loading dose of 20 to 35 mg/kg (maximum dose 3000 mg); initial maintenance dose based on nomogram, and subsequent dose adjustments based on AUC-guided or trough-guided monitoring plus Rifampin§ 900 mg per 24 hours IV or orally in 3 divided doses for ≥6 weeks plus Gentamicin¥‡ 3 mg/kg per 24 hours IV or IM in 2 or 3 divided doses for 2 weeks | Vancomycin¶¶ 40 mg/kg per 24 hours IV (maximum dose: 2 g per 24 hours) in 2 or 3 divided doses for ≥6 weeks plus Rifampin§ (refer to dosing above) for ≥6 weeks plus Gentamicin¥‡ (refer to dosing above) for first 2 weeks | Either Vancomycin¶¶ 30 to 60 mg/kg per 24 hours IV in 2 or 3 divided doses for ≥6 weeks or Daptomycin** 10 mg/kg per 24 hours IV once daily for ≥6 weeks plus Rifampin§ 900 to 1200 mg per 24 hours IV or orally in 2 or 3 divided doses for ≥6 weeks plus Gentamicin¥‡ 3 mg/kg per 24 hours IV or IM in 1 (preferred) or 2 divided doses for first 2 weeks |
The doses in this table 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 intramuscular administration is provided as an alternative, intravenous route is preferred, particularly in infants and children.AUC: area under the 24-hour time-concentration curve; IM: intramuscularly; IV: intravenously; PVE: prosthetic valve endocarditis.
* Consultation with a pediatric infectious disease specialist is recommended.
¶ Patients with infection due to methicillin-susceptible Staphylococcus aureus (MSSA) and severe hypersensitivity to penicillins and cephalosporins may be treated with vancomycin or daptomycin as an alternative to nafcillin, oxacillin, or cefazolin. In such patients, an allergy evaluation should be conducted; if presence of immediate hypersensitivity is questionable, skin testing should be pursued. Beta-lactam desensitization may be attempted in stable patients.
Δ Initial treatment with nafcillin or oxacillin is preferred if feasible; refer to topic on treatment of PVE for further discussion.
◊ For use in patients with nonsevere penicillin allergy. Avoid cefazolin in complicating brain abscess; nafcillin is preferred.
§ Rifampin is believed to help eradicate bacteria attached to foreign material. It should always be used in combination with another effective antistaphylococcal drug (ideally 2 active agents) to minimize risk of emergent resistance. Rifampin increases hepatic clearance of warfarin and other drugs. Rifampin should be started 3 to 5 days after initiation of the primary antistaphylococcal agent (beta-lactam, vancomycin, or daptomycin) and gentamicin.
¥ Gentamicin is recommended for PVE and, in non-obese adults, is based on ideal body weight. Kidney function and serum gentamicin concentrations should be monitored at least once per week. When given in 2 or 3 divided doses (per AHA guidance), pre-dose (trough) concentrations should be <1 mcg/mL and post-dose (peak, 1 hour after infusion) concentrations should be between 3 and 4 mcg/mL. When given in a single daily dose (per ESC guidance), 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).
‡ For patients with an aminoglycoside-resistant organism, refer to text 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[2].
** The regimen of daptomycin, rifampin, and gentamicin may be used in the following circumstances: (1) patients with MSSA infection who are intolerant of beta-lactams and cannot undergo desensitization; (2) patients with infection due to a methicillin-resistant S. aureus (MRSA) isolate with vancomycin MIC is >1; (3) patients with infection due to a methicillin heteroresistant S. aureus wherein there is a subpopulation with vancomycin MIC >2; or (4) patients with high risk of nephrotoxicity precluding coadministration of vancomycin and gentamicin. If gentamicin is to be avoided entirely, daptomycin should be given in combination with ceftaroline and rifampin.
¶¶ Vancomycin dosing in the 2015 AHA guidelines[3] consists of 30 mg/kg per 24 hours IV in 2 divided doses for 6 weeks, with target trough concentrations of 10 to 20 mcg/mL; some favor trough concentrations of 15 to 20 mcg/mL. 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. Special dosing considerations apply in patients with unstable kidney function, on kidney replacement therapy, or with obesity. Refer to the UpToDate topic on vancomycin dosing for sample nomogram and discussion of AUC-guided and trough-guided vancomycin dosing.