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Suggested regimens for therapy of prosthetic valve endocarditis due to strains of viridans streptococci and Streptococcus gallolyticus (bovis) relatively or fully resistant to penicillin G *

Suggested regimens for therapy of prosthetic valve endocarditis due to strains of viridans streptococci and Streptococcus gallolyticus (bovis) relatively or fully resistant to penicillin G *
American Heart Association (AHA) European Society of Cardiology (ESC)

 Adult

(MIC >0.12 mcg/mL)

Pediatric

(MIC >0.1 mcg/mL)

Adult

(MIC ≥0.25 mcg/mL)

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

CeftriaxoneΔ 2 g/24 hours IV in 1 dose for six weeks

plus

Gentamicin◊§ 3 mg/kg per 24 hours IV or IM in 1 dose for 6 weeks

Monotherapy:

Vancomycin¥ 30 mg/kg per 24 hours IV in 2 divided doses 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

Gentamicin◊ 3 to 6 mg/kg per 24 hours IV in 3 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 plus gentamicin (dosing as above) for first 2 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 200 mg/kg per 24 hours IV in 4 or 6 divided doses for 6 weeks

or

CeftriaxoneΔ 2 g per 24 hours IV in 1 dose for 6 weeks

or

Ampicillin 12 g per 24 hours (or 200 mg/kg per 24 hours) in 4 or 6 divided doses for 6 weeks

or

Vancomycin¥ ​30 mg/kg per 24 hours IV in 2 doses for 6 weeks

plus

Gentamicin◊§ 3 mg/kg per 24 hours IV or IM in 1 dose for 6 weeks
The doses above 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 individual Lexicomp drug monographs for renal dose adjustments.
​Wherever intramuscular administration is provided as an alternative, intravenous route is preferred, particularly in infants and children.
MIC: minimum inhibitory concentration; IV: intravenously; IM: intramuscularly; PVE: prosthetic valve endocarditis.
* Refer to the UpToDate topic on treatment of PVE for approach to treatment of PVE due to Abiotrophia defectiva, Granulicatella spp, and Gemella spp.
¶ AHA adult guidelines define relatively resistant streptococcal strains as MIC >0.12 mcg/mL and <0.5 mcg/mL; AHA pediatric guidelines use MIC >0.1 mcg/mL and <0.5 mcg/mL; ESC guidelines use MIC 0.25 to 2 mcg/mL. AHA guidelines define resistant streptococcal strains as MIC ≥0.5 mcg/mL. ESC guidelines use MIC >2 mcg/mL. For fully penicillin-resistant strains (per AHA, MIC ≥0.5 mcg/mL), vancomycin monotherapy should be used; we do not give gentamicin with vancomycin because of the increased risk of nephrotoxicity with coadministration of these agents.
Δ Alternative in patients with nonsevere penicillin allergy; preferred for outpatient therapy.
◊ In adults, aminoglycosides are dosed 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, one hour after infection) 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, postdose (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). 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; refer to the UpToDate topic on treatment of PVE for further discussion.
¥ Vancomycin therapy only recommended for patients allergic to penicillin and cephalosporins. Penicillin desensitization can be attempted in stable patients. In adults, vancomycin is dosed based on actual body weight. The dose should be adjusted for trough concentration of 10 to 15 mcg/mL.
Data from:
  1. 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.
  2. 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.
  3. 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.
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