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Pathogen-Based Therapy Adapted from Circulation 2005;111(23):e394-434. and Circulation 2008;118(15):e523-661.

Viridans Streptococci or Streptococcus bovis

▸ Click on the following categories to expand treatment regimens.

Native Valve Endocarditis   ▸  Highly PCN Susceptible, Adult   ▸  Highly PCN Susceptible, Pediatric   ▸  Relatively PCN Resistant, Adult   ▸  Relatively PCN Resistant, Pediatric   ▸  Highly PCN Resistant Prosthetic Valve Endocarditis   ▸  PCN Susceptible, Adult   ▸  PCN Susceptible, Pediatric   ▸  PCN Resistant, Adult   ▸  PCN Resistant, Pediatric

Viridans Streptococci or S. bovis NVE, Penicillin MIC ≤0.12 μg/mL, Adult Preferred Regimen† ▸ Penicillin G 12—18 MU/day IV continuously or q4—6h x 4 weeks OR ▸ Ceftriaxone 2 g IV/IM q24h x 4 weeks Alternative Regimen 1‡ ▸ Penicillin G 12—18 MU/day IV continuously or q4—6h x 2 weeks OR ▸ Ceftriaxone 2 g IV/IM q24h x 2 weeks PLUS ▸ Gentamicin 3 mg/kg IV/IM q24h (or 1 mg/kg IV/IM q8h) x 2 weeks¶ Alternative Regimen 2 ▸ Vancomycin 15 mg/kg IV q12h x 4 weeksǁ † Preferred in most patients greater than 65 y of age or patients with impairment of 8th cranial nerve function or renal function. ‡ Two-week regimen not intended for patients with known cardiac or extracardiac abscess or for those with creatinine clearance of less than 20 ml per min, impaired 8th cranial nerve function, or Abiotrophia, Granulicatella, or Gemella infection. ¶ Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ǁ Recommended only for patients unable to tolerate penicillin or ceftriaxone. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Viridans Streptococci or S. bovis NVE, Penicillin MIC ≤0.12 μg/mL, Pediatric Preferred Regimen† ▸ Penicillin G 0.2 MU/kg/day IV q4—6h x 4 weeks OR ▸ Ceftriaxone 100 mg/kg IV/IM q24h x 4 weeks Alternative Regimen 1‡ ▸ Penicillin G 0.2 MU/kg/day IV q4—6h x 2 weeks OR ▸ Ceftriaxone 100 mg/kg IV/IM q24h x 2 weeks PLUS ▸ Gentamicin 3 mg/kg IV/IM q24h (or 1 mg/kg IV/IM q8h) x 2 weeks¶ Alternative Regimen 2 ▸ Vancomycin 40 mg/kg/day IV q8—12h x 4 weeksǁ † Preferred in most patients greater than 65 y of age or patients with impairment of 8th cranial nerve function or renal function. ‡ Two-week regimen not intended for patients with known cardiac or extracardiac abscess or for those with creatinine clearance of less than 20 ml per min, impaired 8th cranial nerve function, or Abiotrophia, Granulicatella, or Gemella infection. ¶ Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ǁ Recommended only for patients unable to tolerate penicillin or ceftriaxone. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Viridans Streptococci or S. bovis NVE, Penicillin MIC >0.12 to ≤0.5 μg/ml, Adult Preferred Regimen ▸ Penicillin G 24 MU/day IV continuously or q4—6h x 4 weeks† OR ▸ Ceftriaxone 2 g IV/IM q24h x 4 weeks‡ PLUS ▸ Gentamicin 3 mg/kg IV/IM q24h (1 mg/kg IV/IM q8h) x 2 weeks¶ Alternative Regimen ▸ Vancomycin 15 mg/kg/day IV q12h x 4 weeksǁ † Patients with endocarditis caused by Penicillin Resistant (MIC greater than 0.5 μg/ml) strains should be treated with regimen recommended for enterococcal endocarditis. ‡ Recommended for enterococcal endocarditis. ¶ Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ǁ Recommended only for patients unable to tolerate penicillin or ceftriaxone. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Viridans Streptococci or S. bovis NVE, Penicillin MIC >0.12 to ≤0.5 μg/ml, Pediatric Preferred Regimen ▸ Penicillin G 0.3 MU/kg/day IV q4—6h x 4 weeks† OR ▸ Ceftriaxone 100 mg/kg IV/IM q24h x 4 weeks‡ PLUS ▸ Gentamicin 3 mg/kg IV/IM q24h (or 1 mg/kg IV/IM q8h) x 2 weeks¶ Alternative Regimen ▸ Vancomycin 40 mg/kg IV q8—12h x 4 weeksǁ † Patients with endocarditis caused by Penicillin Resistant (MIC greater than 0.5 μg/ml) strains should be treated with regimen recommended for enterococcal endocarditis. ‡ Recommended for enterococcal endocarditis. ¶ Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ǁ Recommended only for patients unable to tolerate penicillin or ceftriaxone. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Viridans Streptococci or S. bovis NVE, Penicillin MIC >0.5 μg/ml ▸ Endocarditis caused by highly penicillin resistant (MIC >0.5 μg/ml) strains of viridans streptococci, Abiotrophia defectiva, Granulicatella species, and Gemella species should be treated with a regimen that is recommended for enterococcal endocarditis. Viridans Streptococci or S. bovis PVE, Penicillin MIC ≤0.12 μg/ml, Adult Preferred Regimen ▸ Penicillin G 24 MU/day IV continuously or q4—6h x 6 weeks OR ▸ Ceftriaxone 2 g IV/IM q24h x 6 weeks WITH OR WITHOUT ▸ Gentamicin 3 mg/kg IV/IM q24h (or 1 mg/kg IV/IM q8h) x 2 weeks¶ Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 6 weeksǁ ¶ Gentamicin therapy should not be administered to patients with creatinine clearance of <30 mL/min ǁ Recommended only for patients unable to tolerate penicillin or ceftriaxone. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Viridans Streptococci or S. bovis PVE, Penicillin MIC ≤0.12 μg/ml, Pediatric Preferred Regimen ▸ Penicillin G 0.3 MU/kg/day IV q4—6h x 6 weeks OR ▸ Ceftriaxone 100 mg/kg IV/IM q24h x 6 weeks WITH OR WITHOUT ▸ Gentamicin 3 mg/kg IV/IM q24h (or 1 mg/kg IV/IM q8h) x 2 weeks¶ Alternative Regimen ▸ Vancomycin 40 mg/kg/day IV q8—12h x 6 weeksǁ ¶ Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ǁ Recommended only for patients unable to tolerate penicillin or ceftriaxone. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Viridans Streptococci or S. bovis PVE, Penicillin MIC >0.12 μg/ml, Adult Preferred Regimen ▸ Penicillin G 24 MU/day IV continuously or q4—6h x 6 weeks OR ▸ Ceftriaxone 2 g IV/IM q24h x 6 weeks PLUS ▸ Gentamicin 3 mg/kg IV/IM q24h (or 1 mg/kg IV/IM q8h) x 6 weeks¶ Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 6 weeksǁ ¶ Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ǁ Recommended only for patients unable to tolerate penicillin or ceftriaxone. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Viridans Streptococci or S. bovis PVE, Penicillin MIC >0.12 μg/ml, Pediatric Preferred Regimen ▸ Penicillin G 0.3 MU/kg/day IV q4—6h x 6 weeks OR ▸ Ceftriaxone 100 mg/kg IV/IM q24h x 6 weeks PLUS ▸ Gentamicin 3 mg/kg IV/IM q24h (or 1 mg/kg IV/IM q8h) x 6 weeks¶ Alternative Regimen ▸ Vancomycin 40 mg/kg/day IV q8—12h x 6 weeksǁ ¶ Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ǁ Recommended only for patients unable to tolerate penicillin or ceftriaxone. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome.

Streptococcus pneumoniae, Streptococcus pyogenes, and Groups B, C, and G Streptococci

▸ Click on the following categories to expand treatment regimens.

Streptococcus pneumoniae   ▸  PCN Susceptible   ▸  PCN Resistant, Without Meningitis   ▸  PCN Resistant, With Meningitis Streptococcus pyogenes   ▸  S. pyogenes Endocarditis Group B, C, and G Streptococcus   ▸  Group B, C, and G Streptococcus Endocarditis

S. pneumoniae Endocarditis, PCN Susceptible (MIC ≤0.1 μg/mL) Preferred Regimen ▸ Penicillin G 12—18 MU/day IV continuously or q4—6h x 4 weeks OR ▸ Cefazolin 1—1.5 g IV q6h x 4 weeks OR ▸ Ceftriaxone 2 g IV q24h x 4 weeks Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 4 weeksǁ ǁ Recommended only for patients unable to tolerate β-lactams. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. S. pneumoniae Endocarditis, PCN Resistant (MIC >0.1 μg/mL), Without Meningitis Preferred Regimen ▸ Penicillin G 24 MU/day IV continuously or q4—6h x 4 weeks OR ▸ Cefotaxime 2 g IV q6—8h x 4 weeks OR ▸ Ceftriaxone 2 g IV q24h x 4 weeks Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 4 weeksǁ ǁ Recommended only for patients unable to tolerate β-lactams. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. S. pneumoniae Endocarditis, PCN Resistant (MIC >0.1 μg/mL), With Meningitis Preferred Regimen ▸ Cefotaxime 2 g IV q4—6h x 4 weeks OR ▸ Ceftriaxone 2 g IV q12h x 4 weeks PLUS ▸ Vancomycin 15 mg/kg IV q6h x 4 weeks PLUS ▸ Rifampin 600 mg IV q24h x 4 weeks S. pyogenes Endocarditis Preferred Regimen ▸ Penicillin G 12—18 MU/day IV continuously or q4—6h x 4 weeks OR ▸ Cefazolin 1—1.5 g IV q6h x 4 weeks OR ▸ Ceftriaxone 2 g IV q24h x 4 weeks Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 4 weeksǁ ǁ Recommended only for patients unable to tolerate β-lactams. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Group B, C, or G Streptococcus Endocarditis Preferred Regimen ▸ Penicillin G 24 MU/day IV continuously or q4—6h x 4—6 weeks OR ▸ Ceftriaxone 2 g IV/IM q24h x 4—6 weeks PLUS ▸ Gentamicin 3 mg/kg IV/IM q24h (1 mg/kg IV/IM q8h) x 2 weeks¶ Alternative Regimen ▸ Vancomycin 15 mg/kg/day IV q12h x 4—6 weeksǁ ¶ Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ǁ Recommended only for patients unable to tolerate penicillin or ceftriaxone. Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome.

Staphylococcus

▸ Click on the following categories to expand treatment regimens.

Native Valve Endocarditis   ▸  Oxacillin Susceptible, Adult   ▸  Oxacillin Susceptible, Pediatric   ▸  Oxacillin Resistant, Adult   ▸  Oxacillin Resistant, Pediatric Prosthetic Valve Endocarditis   ▸  Oxacillin Susceptible, Adult   ▸  Oxacillin Susceptible, Pediatric   ▸  Oxacillin Resistant, Adult   ▸  Oxacillin Resistant, Pediatric

Staphylococcal NVE, Oxacillin Susceptible, Adult Preferred Regimen† ▸ Nafcillin 12 g/day IV q4—6h x 6 weeks OR ▸ Oxacillin 12 g/day IV q4—6h x 6 weeks WITH OR WITHOUT ▸ Gentamicin 3 mg/kg/day IV/IM q8—12h x 3—5 days¶ Alternative Regimen‡ ▸ Cefazolin 2 g IV q8h x 6 weeks§ WITH OR WITHOUT ▸ Gentamicin 3 mg/kg/day IV/IM q8—12h x 3—5 days¶ † For complicated right-sided IE and for left-sided IE; for uncomplicated right-sided IE, 2 weeks. ¶ Gentamicin should be administered in close proximity to vancomycin, nafcillin, or oxacillin dosing. Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ‡ For penicillin-allergic (nonanaphylactoid type) patients; consider skin testing for oxacillin-susceptible staphylococci and questionable history of immediate-type hypersensitivity to penicillin. § Cephalosporins should be avoided in patients with anaphylactoid-type hypersensitivity to β-lactams; vancomycin should be used in these cases. Staphylococcal NVE, Oxacillin Susceptible, Pediatric Preferred Regimen† ▸ Nafcillin 200 mg/kg/day IV q4—6h x 6 weeks OR ▸ Oxacillin 200 mg/kg/day IV q4—6h x 6 weeks WITH OR WITHOUT ▸ Gentamicin 1 mg/kg IV/IM q8h x 3—5 days¶ Alternative Regimen‡ ▸ Cefazolin 100 mg/kg/day IV q8h x 6 weeks§ WITH OR WITHOUT ▸ Gentamicin 1 mg/kg IV/IM q8h x 3—5 days¶ † For complicated right-sided IE and for left-sided IE; for uncomplicated right-sided IE, 2 weeks. ¶ Gentamicin should be administered in close proximity to vancomycin, nafcillin, or oxacillin dosing. Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. ‡ For penicillin-allergic (nonanaphylactoid type) patients; consider skin testing for oxacillin-susceptible staphylococci and questionable history of immediate-type hypersensitivity to penicillin. § Cephalosporins should be avoided in patients with anaphylactoid-type hypersensitivity to β-lactams; vancomycin should be used in these cases. Staphylococcal NVE, Oxacillin Resistant, Adult Preferred Regimen ▸ Vancomycin 15 mg/kg IV q12h x 6 weeksǁ Alternative Regimen ▸ Linezolid 600 mg IV/PO q12h x 8 weeks OR ▸ Daptomycin 6 mg/kg IV q24h x 2—6 weeks ǁ Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Staphylococcal NVE, Oxacillin Resistant, Pediatric Preferred Regimen ▸ Vancomycin 40 mg/kg/day IV q8—12h x 6 weeksǁ Alternative Regimen ▸ Linezolid 10 mg/kg IV/PO q8h x 8 weeks ǁ Vancomycin doses should not exceed 2 g per 24 h, unless serum concentrations are inappropriately low. Dosage should be adjusted to obtain peak (1 h after infusion completed) serum concentration of 30–45 μg/ml and a trough concentration range of 10–15 μg/ml. Vancomycin should be infused during course of at least 1 h to reduce risk of histamine-release red man syndrome. Staphylococcal PVE, Oxacillin Susceptible, Adult Preferred Regimen† ▸ Nafcillin 2 g IV q4h x ≥6 weeks OR ▸ Oxacillin 2 g IV q4h x ≥6 weeks PLUS ▸ Rifampin 300 mg IV/PO q8h x ≥6 weeks PLUS ▸ Gentamicin 3 mg/kg/day IV/IM q8—12h x 2 weeks¶ † Penicillin G 24 million U/24 h IV in 4 to 6 equally divided doses may be used in place of nafcillin or oxacillin if strain is penicillin susceptible (minimum inhibitory concentration ≤0.1 μg/mL) and does not produce β-lactamase; vancomycin should be used in patients with immediate-type hypersensitivity reactions to β-lactam antibiotics; cefazolin may be substituted for nafcillin or oxacillin in patients with non–immediate-type hypersensitivity reactions to penicillins. ¶ Gentamicin should be administered in close proximity to vancomycin, nafcillin, or oxacillin dosing. Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy. Staphylococcal PVE, Oxacillin Susceptible, Pediatric Preferred Regimen† ▸ Nafcillin 200 mg/kg/day IV q4—6h x ≥6 weeks OR ▸ Oxacillin 2 g IV q4h x ≥6 weeks PLUS ▸ Rifampin 20 mg/kg/day IV/PO q8h x ≥6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 2 weeks¶ † Penicillin G 24 million U/24 h IV in 4 to 6 equally divided doses may be used in place of nafcillin or oxacillin if strain is penicillin susceptible (minimum inhibitory concentration ≤0.1 μg/mL) and does not produce β-lactamase; vancomycin should be used in patients with immediate-type hypersensitivity reactions to β-lactam antibiotics; cefazolin may be substituted for nafcillin or oxacillin in patients with non–immediate-type hypersensitivity reactions to penicillins. ¶ Gentamicin should be administered in close proximity to vancomycin, nafcillin, or oxacillin dosing. Gentamicin dosage should be adjusted to achieve peak serum concentration of 3—4 μg/ml and trough serum concentration of less than 1 μg/ml when 3 divided doses are used; nomogram used for single daily dosing; other potentially nephrotoxic drugs (e.g., nonsteroidal anti-inflammatory drugs) should be used with caution in patients receiving gentamicin therapy.