Endocarditis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Ahmed Zaghw, M.D. [3]; Mohamed Moubarak, M.D. [4]

Overview

Blood cultures should be drawn prior to instituting antibiotics to identify the etiologic agent and to determine its antimicrobial susceptibility. Older antibiotics such as penicillin G, ampicillin, nafcillin, cefazolin, gentamycin, ceftriaxone, rifampin and vancomycin are the mainstays of therapy. Empiric antiomicrobial therapy is started once the blood cultures have been collected.

Timing of Initiation of Antibiotics

Antibiotic therapy for subacute or indolent disease can be delayed until results of blood cultures are known; in fulminant infection or valvular dysfunction requiring urgent surgical intervention, begin empirical antibiotic therapy promptly after blood cultures have been obtained.

Duration of Antibiotic Therapy

The duration for native valve endocarditis is often 4 weeks. For prosthetic valve endocarditis (including the presence of a valve ring), treatment should be continued for 6 to 8 weeks. For each infective agent, the preferred antimicrobial agent, dose, and duration is listed below.

Empirical Antibiotic Therapy

• Antibiotic therapy for subacute hemodynamically stable disease, and in those who have received antibiotics recently can be delayed waiting for the results of blood cultures, as this delay allows an additional blood cultures without the confounding effect of empiric treatment, which is very important in determining the causing pathogens.

• On the other hand, the rapid progression of acute cases necessitates the start of empirical treatment antibiotic therapy once the blood cultures have been collected.

• Empirical therapy is needed for all likely pathogens, certain antibiotic agents, including aminoglycosides, is preferably avoided for its toxic effects.

• Clinical course of infection beside the epidemiological features should be considered upon selecting empirical treatment regimen.

• Consultation with an infectious disease specialist for the selection of one of the antibiotic regimens is recommended (see therapy for culture-negative endocarditis).

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 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 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. Staphylococcal PVE, Oxacillin Resistant, Adult Preferred Regimen ▸ Vancomycin 15 mg/kg IV q12h x ≥6 weeksǁ PLUS ▸ Rifampin 300 mg IV/PO q8h x ≥6 weeks PLUS ▸ Gentamicin 3 mg/kg/day IV/IM q8—12h x 2 weeks¶ 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. ¶ 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 Resistant, Pediatric Preferred Regimen† ▸ Vancomycin 40 mg/kg/day IV q8—12h x ≥6 weeksǁ PLUS ▸ Rifampin 20 mg/kg/day IV/PO q8h x ≥6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 2 weeks¶ 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. ¶ 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.

Enterococcus

▸ Click on the following categories to expand treatment regimens.

PCN/GM/VM Susceptible   ▸  PCN/GM/VM Susceptible, Adult   ▸  PCN/GM/VM Susceptible, Pediatric PCN/VM Susceptible, GM Resistant   ▸  PCN/VM Susceptible, GM Resistant, Adult   ▸  PCN/VM Susceptible, GM Resistant, Pediatric VM/AG Susceptible, PCN Resistant   ▸  VM/AG Susceptible, PCN Resistant, Adult   ▸  VM/AG Susceptible, PCN Resistant, Pediatric PCN/VM/AG Resistant   ▸  PCN/VM/AG Resistant, Adult   ▸  PCN/VM/AG Resistant, Pediatric

Enterococcal Endocarditis, PCN/GM/VM Susceptible, Adult Preferred Regimen† ▸ Ampicillin 2 g IV q4h x 4—6 weeks OR ▸ Penicillin G 18—30 MU/day IV continuously or q4h x 4—6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 4—6 weeks¶ Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 6 weeksǁ PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 6 weeks¶ † Native valve: 4-wk therapy recommended for patients with symptoms of illness ≤3 mo; 6-wk therapy recommended for patients with symptoms >3 mo. Prosthetic valve or other prosthetic cardiac material: minimum of 6 wk of therapy recommended. ¶ Gentamicin should be administered in close proximity to vancomycin 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. ǁ Vancomycin therapy recommended only for patients unable to tolerate penicillin or ampicillin. Six wk of vancomycin therapy recommended because of decreased activity against enterococci. 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. Enterococcal Endocarditis, PCN/GM/VM Susceptible, Pediatric Preferred Regimen† ▸ Ampicillin 300 mg/kg/day IV q4—6h x 4—6 weeks OR ▸ Penicillin G 0.3 MU/kg/day IV q4—6h x 4—6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 4—6 weeks¶ Alternative Regimen ▸ Vancomycin 40 mg/kg/day IV q8—12h x 6 weeksǁ PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 6 weeks¶ † Native valve: 4-wk therapy recommended for patients with symptoms of illness ≤3 mo; 6-wk therapy recommended for patients with symptoms >3 mo. Prosthetic valve or other prosthetic cardiac material: minimum of 6 wk of therapy recommended. ¶ Gentamicin should be administered in close proximity to vancomycin 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. ǁ Vancomycin therapy recommended only for patients unable to tolerate penicillin or ampicillin. Six wk of vancomycin therapy recommended because of decreased activity against enterococci. 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. Enterococcal Endocarditis, PCN/VM Susceptible, GM Resistant, Adult Preferred Regimen† ▸ Ampicillin 2 g IV q4h x 4—6 weeks OR ▸ Penicillin G 24 MU/day IV continuously or q4h x 4—6 weeks PLUS ▸ Streptomycin 7.5 mg/kg IV/IM q12h x 4—6 weeks¶ Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 6 weeksǁ PLUS ▸ Streptomycin 7.5 mg/kg IV/IM q12h x 6 weeks¶ † Native valve: 4-wk therapy recommended for patients with symptoms of illness ≤3 mo; 6-wk therapy recommended for patients with symptoms >3 mo. Prosthetic valve or other prosthetic cardiac material: minimum of 6 wk of therapy recommended. ¶ Streptomycin dosage adjusted to achieve a 1-hour serum concentration of 20 to 35 μg/mL and a trough concentration of <10 μg/mL Patients with a creatinine clearance of <50 mL/min should be treated in consultation with an infectious diseases specialist. ǁ Vancomycin therapy recommended only for patients unable to tolerate penicillin or ampicillin. Six wk of vancomycin therapy recommended because of decreased activity against enterococci. 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. Enterococcal Endocarditis, PCN/VM Susceptible, GM Resistant, Pediatric Preferred Regimen† ▸ Ampicillin 300 mg/kg/day IV q4—6h x 4—6 weeks OR ▸ Penicillin G 0.3 MU/kg/day IV q4—6h x 4—6 weeks PLUS ▸ Streptomycin 40 mg/kg/day IV q8—12h x 6 weeks¶ Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 6 weeksǁ PLUS ▸ Streptomycin 10—15 mg/kg IV/IM q12h x 6 weeks¶ † Native valve: 4-wk therapy recommended for patients with symptoms of illness ≤3 mo; 6-wk therapy recommended for patients with symptoms >3 mo. Prosthetic valve or other prosthetic cardiac material: minimum of 6 wk of therapy recommended. ¶ Streptomycin dosage adjusted to achieve a 1-hour serum concentration of 20 to 35 μg/mL and a trough concentration of <10 μg/mL Patients with a creatinine clearance of <50 mL/min should be treated in consultation with an infectious diseases specialist. ǁ Vancomycin therapy recommended only for patients unable to tolerate penicillin or ampicillin. Six wk of vancomycin therapy recommended because of decreased activity against enterococci. 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.

Gram-Negative Bacteria

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Gram-Negative Bacteria   ▸  Bartonella spp.   ▸  Escherichia coli   ▸  HACEK Microorganisms   ▸  Klebsiella spp.   ▸  Neisseria spp.   ▸  Proteus mirabilis   ▸  Pseudomonas aeruginosa

Suspected Bartonella Endocarditis, Culture Negative Preferred Regimen† ▸ Ceftriaxone 2 g IV/IM q24h x 6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 2 weeks¶ WITH OR WITHOUT ▸ Doxycycline 100 mg IV/PO q12h x 6 weeks Documented Bartonella Endocarditis, Culture Positive Preferred Regimen ▸ Doxycycline 100 mg IV/PO q12h x 6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 2 weeks¶ Alternative Regimen ▸ Doxycycline 100 mg IV/PO q12h x 6 weeks PLUS ▸ Rifampin 300 mg PO/IV q12h x 6 weeks † Patients with Bartonella endocarditis should be treated in consultation with an infectious diseases specialist. ¶ 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. Escherichia coli Endocarditis Preferred Regimen ▸ Ampicillin 2 g IV q4h x 4—6 weeks OR ▸ Penicillin G 20 MU/day IV continuously x 4—6 weeks OR ▸ Ceftriaxone 2 g IV/IM q24h x 4—6 weeks PLUS ▸ Gentamicin 1.7 mg/kg IV/IM q8h x 2 weeks¶ ¶ 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. HACEK Endocarditis, Adult† Preferred Regimen ▸ Ceftriaxone 2 g IV/IM q24h x 4 weeks‡ Alternative Regimen ▸ Ampicillin-Sulbactam 1.5 g IV q6h x 4 weeks OR ▸ Ciprofloxacin 500 mg PO q12h (or 400 mg IV q12h) x 4 weeks§ HACEK Endocarditis, Pediatric† Preferred Regimen ▸ Ceftriaxone 100 mg/kg IV/IM q24h x 4 weeks‡ Alternative Regimen ▸ Ampicillin-Sulbactam 300 mg/kg/day IV q4—6h x 4 weeks OR ▸ Ciprofloxacin 10—15 mg/kg IV/PO q12h x 4 weeks§ † Prosthetic valve: patients with endocarditis involving prosthetic cardiac valve or other prosthetic cardiac material should be treated for 6 wk. ‡ Cefotaxime or another third- or fourth-generation cephalosporin may be substituted. § Fluoroquinolone therapy recommended only for patients unable to tolerate cephalosporin and ampicillin therapy; levofloxacin, gatifloxacin, or moxifloxacin may be substituted; fluoroquinolones generally not recommended for patients <18 y old. Klebsiella Endocarditis Preferred Regimen† ▸ Ceftriaxone 2 g IV/IM q24h x 4 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 2 weeks¶ OR ▸ Amikacin 15 mg/kg/day IV q8—12h x 2 weeks§ Alternative Regimen ▸ Piperacillin/Tazobactam 3.375 g IV q6h x 4 weeks ¶ 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. § Peak concentrations (30 to 90 minutes after injection) above 35 μg/mL and trough concentrations (just prior to the next dose) above 10 μg/mL should be avoided. Dosage should be adjusted as indicated. Neisseria 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 † Infectious disease consultation should be obtained in cases in which Neisseria are resistant to penicillin. Proteus mirabilis Endocarditis Preferred Regimen ▸ Ampicillin 2 g IV q4h x 4—6 weeks OR ▸ Penicillin G 20 MU/day IV continuously x 4—6 weeks OR ▸ Ceftriaxone 2 g IV/IM q24h x 4—6 weeks PLUS ▸ Gentamicin 1.7 mg/kg IV/IM q8h x 2 weeks¶ ¶ 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. Pseudomonas aeruginosa Endocarditis Preferred Regimen ▸ Ticarcillin 3 g IV q4h (or 4 g IV q6h) x ≥6 weeks OR ▸ Piperacillin/Tazobactam 3.375 gm IV q4h (or 4.5 g IV q6h) x ≥6 weeks OR ▸ Ceftazidime 2 g IV q8h x ≥6 weeks OR ▸ Cefepime 2 g IV q8h x ≥6 weeks PLUS ▸ Tobramycin 8 mg/kg IV/IM q24h x ≥6 weeks¶ ¶ Maintenance of peak and trough concentrations of 15—20 μg/mL and ≤2 μg/mL, respectively.

Culture-Negative Endocarditis Adapted from Circulation 2005;111(23):e394-434. and Circulation 2008;118(15):e523-661.

▸ Click on the following categories to expand treatment regimens.

Native Valve Endocarditis   ▸  Culture-Negative NVE, Adult   ▸  Culture-Negative NVE, Pediatric Prosthetic Valve Endocarditis   ▸  Culture-Negative PVE, Adult (Early, ≤1 year)   ▸  Culture-Negative PVE, Pediatric (Early, ≤1 year)   ▸  Culture-Negative PVE, Adult (Late, >1 year)   ▸  Culture-Negative PVE, Adult (Late, >1 year)

Culture-Negative Native Valve Endocarditis, Adult Preferred Regimen ▸ Ampicillin-Sulbactam 3 g IV q6h x 4—6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 4—6 weeks¶ Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 4—6 weeksǁ PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 4—6 weeks¶ PLUS ▸ Ciprofloxacin 500 mg PO q12h (or 400 mg IV q12h) x 4—6 weeks ¶ 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 penicillins. 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. Culture-Negative Native Valve Endocarditis, Pediatric Preferred Regimen ▸ Ampicillin-Sulbactam 300 mg/kg/day IV q4—6h x 4—6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 4—6 weeks¶ Alternative Regimen ▸ Vancomycin 40 mg/kg/day IV q8—12h x 4—6 weeksǁ PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 4—6 weeks¶ PLUS ▸ Ciprofloxacin 10—15 mg/kg IV/PO q12h x 4—6 weeks ¶ 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 penicillins. 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. Culture-Negative Prosthetic Valve Endocarditis, Adult (Early, ≤1 year) Preferred Regimen ▸ Vancomycin 15 mg/kg IV q12h x 6 weeksǁ PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 2 weeks¶ PLUS ▸ Cefepime 2 g IV q8h x 6 weeks PLUS ▸ Rifampin 300 mg PO/IV q8h x 6 weeks ǁ Recommended only for patients unable to tolerate penicillins. 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. ¶ 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. Culture-Negative Prosthetic Valve Endocarditis, Pediatric (Early, ≤1 year) Preferred Regimen ▸ Vancomycin 40 mg/kg/day IV q8—12h x 6 weeksǁ PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 2 weeks¶ PLUS ▸ Cefepime 50 mg/kg IV q8h x 6 weeks PLUS ▸ Rifampin 20 mg/kg/day PO/IV q8h x 6 weeks ǁ Recommended only for patients unable to tolerate penicillins. 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. ¶ 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. Culture-Negative Prosthetic Valve Endocarditis, Adult (Late, >1 year) Preferred Regimen ▸ Ampicillin-Sulbactam 3 g IV q6h x 6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 6 weeks¶ PLUS ▸ Rifampin 300 mg PO/IV q8h x 6 weeks Alternative Regimen ▸ Vancomycin 15 mg/kg IV q12h x 6 weeksǁ PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 6 weeks¶ PLUS ▸ Ciprofloxacin 500 mg PO q12h (or 400 mg IV q12h) x 6 weeks PLUS ▸ Rifampin 300 mg PO/IV q8h x 6 weeks ¶ 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 penicillins. 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. Culture-Negative Prosthetic Valve Endocarditis, Pediatric (Late, >1 year) Preferred Regimen ▸ Ampicillin-Sulbactam 300 mg/kg/day IV q4—6h x 6 weeks PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 6 weeks¶ PLUS ▸ Rifampin 20 mg/kg/day PO/IV q8h x 6 weeks Alternative Regimen ▸ Vancomycin 40 mg/kg/day IV q8—12h x 6 weeksǁ PLUS ▸ Gentamicin 1 mg/kg IV/IM q8h x 6 weeks¶ PLUS ▸ Ciprofloxacin 10—15 mg/kg IV/PO q12h x 6 weeks PLUS ▸ Rifampin 20 mg/kg/day PO/IV q8h x 6 weeks ¶ 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 penicillins. 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.