Suggested regimens for therapy of prosthetic valve endocarditis due to Staphylococcus species

Suggested regimens for therapy of prosthetic valve endocarditis due to Staphylococcus species

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^¶: Nafcillin or oxacillin 12 g per 24 hours IV in six divided doses for ≥6 weeks or Cefazolin^Δ 6 g per 24 hours IV in three divided doses for ≥6 weeks plus Rifampin^◊900 mg per 24 hours IV or orally in three divided doses for ≥6 weeks plus Gentamicin^§¥3 mg/kg per 24 hours IV or IM in two or three divided doses for 2 weeks	One of the following^¶: Nafcillin or oxacillin 200 mg/kg per 24 hours IV (maximum dose: 12 g per 24 hours) in four or six divided doses for ≥6 weeks or Cefazolin^Δ 100 mg/kg per 24 hours IV (maximum dose: 6 g per 24 hours) in three divided doses for ≥6 weeks plus Rifampin^◊ 20 mg/kg per 24 hours IV (maximum dose: 900 mg per 24 hours) in three divided doses for ≥6 weeks plus Gentamicin^§¥ 3 to 6 mg/kg per 24 hours IV or IM in three divided doses for first 2 weeks	One of the following^¶: Oxacillin or cloxacillin or flucloxacillin 12 g per 24 hours IV in four or six divided doses for ≥6 weeks or Cefazolin^Δ 6 g per 24 hours IV in three divided doses for ≥6 weeks or Cefotaxime^Δ 6 g per 24 hours IV in three divided doses for ≥6 weeks plus Rifampin^◊ 900 to 1200 mg per 24 hours IV or orally in two or three divided doses for ≥6 weeks plus Gentamicin^§ 3 mg/kg per 24 hours IV or IM in one or two 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 three divided doses for ≥6 weeks plus Gentamicin^§¥ 3 mg/kg per 24 hours IV or IM in two or three divided doses for 2 weeks	Vancomycin^‡ 40 mg/kg per 24 hours IV (maximum dose: 2 g per 24 hours) in two or three divided doses for ≥6 weeks plus Rifampin^◊ (see dosing above) for ≥6 weeks plus Gentamicin^§¥ (see dosing above) for first 2 weeks	Vancomycin^‡ 30 to 60 mg/kg per 24 hours IV in two or three divided doses for ≥6 weeks plus Rifampin^◊900 to 1200 mg per 24 hours IV or orally in two or three divided doses for ≥6 weeks plus Gentamicin^§3 mg/kg per 24 hours IV or IM in one or two divided doses for first 2 weeks

The doses in this table are intended for patients with normal renal function. The doses of many of these agents must be adjusted in the setting of renal insufficiency; refer to the Lexicomp drug-specific monographs for renal dose adjustments.
Wherever intramuscular administration is provided as an alternative, intravenous route is preferred, particularly in infants and children.

PVE: prosthetic valve endocarditis; IV: intravenously; IM: intramuscularly; AUC: area under the 24-hour time-concentration curve
* Consultation with a pediatric infectious disease specialist is recommended.
¶ Patients with infection due to methicillin-susceptible Staphylococcus aureus and severe hypersensitivity to penicillins and cephalosporins may be treated with vancomycin as above 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 For use in patients with nonsevere penicillin allergy. Avoid cefazolin in complicating brain abscess; nafcillin is preferred.
◊ Rifampin is believed to be important in PVE as it may help eradicate bacteria attached to foreign material. It should always be used in combination with another effective antistaphylococcal drug (ideally two active agents) to minimize risk of treatment-emergent resistance. Rifampin increases hepatic clearance of warfarin and other drugs. Starting rifampin three to five days after vancomycin and gentamicin has been suggested by some experts.
§ Gentamicin is recommended for PVE and, in non-obese adults, is based on ideal body weight. Renal function and serum gentamicin concentrations should be monitored at least once per week. When given in three divided doses, 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, pre-dose (trough) concentrations should be <1 mcg/mL. Per ESC guidelines, post-dose (peak, one 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).
¥ If organism is gentamicin resistant, an alternative drug such as another aminoglycoside (eg, amikacin), a fluoroquinolone, or another antimicrobial to which the organism is susceptible may be substituted (refer to the UpToDate topic on antimicrobial therapy of prosthetic valve endocarditis).
‡ Vancomycin dosing in the 2015 AHA guidelines^[1] 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^[5], 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 renal function, on renal 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.

Data from:

Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis in adults: Diagnosis, antimicrobial therapy, and management of complications: A scientific statement for healthcare professionals from the American Heart Association. Circulation 2015; 132:1435.
Baltimore RS, Gewitz M, Baddour LM, et al. Infective Endocarditis in Childhood: 2015 Update: A Scientific Statement From the American Heart Association. Circulation 2015; 132:1487.
Authors/Task Force Members, Habib G, Lancellotti P, et al. 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC) Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J 2015; 36:3075.
Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the Infectious Disease Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. CID 2011; 52:285.
Rybak MJ, Le J, Lodise TP, et al. Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus Aureus Infections: A Revised Consensus Guideline and Review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2020; 77:835.

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Suggested regimens for therapy of prosthetic valve endocarditis due to Staphylococcus species