Endocarditis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Overview

Antimicrobial therapy is the mainstay of therapy for endocarditis. Empiric antimicrobial therapy depends on the nature of the valve (native vs. prosthetic) and the onset of endocarditis following valve implantation (less than 1 year vs. more than 1 year). In patients with endocarditis, antithrombotic therapy may be administered when needed. The prothrombin time must be carefully monitored as anticoagulants may cause or worsen hemorrhage in patients with endocarditis. Heparin administration should be avoided if possible.

Medical Therapy

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.^[1]
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.
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). ^[2]

Timing of Initiation of Antibiotics

Antibiotic therapy for the 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 of 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 are listed below.

Antimicrobial Regimens

Infective endocarditis^[3]

1. Culture-negative endocarditis

1.1. Culture-negative, native valve endocarditis

Preferred regimen: Ampicillin-sulbactam 12 g/24h IV q6h 4–6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 4–6 weeks
Alternative regimen: Vancomycin 30 mg/kg/24h IV q12h for 4–6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 4–6 weeks AND Ciprofloxacin 1000 mg/24 h PO or 800 mg/24h IV q12h for 4–6 weeks
Pediatric dose: Ampicillin-sulbactam 300 mg/kg/24h IV q4–6h; Gentamicin 3 mg/kg/24h IV/IM q8h; Vancomycin 40 mg/kg/24h q8–12h; Ciprofloxacin 20–30 mg/kg/24h IV/PO q12h

1.2. Culture-negative, prosthetic valve endocarditis (early, ≤ 1 year)

Preferred regimen : Vancomycin 30 mg/kg/24h IV q12h for 6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 2 weeks AND Cefepime 6 g/24h IV q8h for 6 weeks AND Rifampin 900 mg/24 h PO/IV q8h for 6 weeks
Pediatric dose: Vancomycin 40 mg/kg/24h IV q8–12h; Gentamicin 3 mg/kg/24h IV/IM q8h; Cefepime 150 mg/kg/24h IV q8h; Rifampin 20 mg/kg/24 h PO/IV q8h

1.3. Culture-negative, prosthetic valve endocarditis (late, > 1 year)

Preferred regimen: Ampicillin-sulbactam 12 g/24h IV q6h 6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 6 weeks
Alternative regimen: Vancomycin 30 mg/kg/24h IV q12h for 4–6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 6 weeks AND Ciprofloxacin 1000 mg/24 h PO or 800 mg/24h IV q12h for 6 weeks
Pediatric dose: Ampicillin-sulbactam 300 mg/kg/24h IV q4h; Gentamicin 3 mg/kg/24h IV/IM q8h; Vancomycin 40 mg/kg/24h q8–12h; Ciprofloxacin 20–30 mg/kg/24h IV/PO q12h

1.4. Culture-negative, prosthetic valve endocarditis (early, ≤ 1 year)

Preferred regimen: Ampicillin-sulbactam 12 g/24h IV q6h 4–6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 4–6 weeks AND Rifampin 900 mg/24 h PO/IV q8h for 6 weeks
Alternative regimen: Vancomycin 30 mg/kg/24h IV q12h for 4–6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 4–6 weeks AND Ciprofloxacin 1000 mg/24 h PO or 800 mg/24h IV q12h for 4–6 weeks AND Rifampin 900 mg/24 h PO/IV q8h for 6 weeks
Pediatric dose: Ampicillin-sulbactam 300 mg/kg/24h IV q4–6h; Gentamicin 3 mg/kg/24h IV/IM q8h; Vancomycin 40 mg/kg/24h IV q8–12h; Cefepime 150 mg/kg/24h IV q8h; Rifampin 20 mg/kg/24 h PO/IV q8h

2. Pathogen-directed antimicrobial therapy

2.1. Bartonella

2.1.1. Suspected Bartonella endocarditis

Preferred regimen : Ceftriaxone sodium 2 g/24h IV/IM in 1 dose for 6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 2 weeks ± Doxycycline 200 mg/kg/24h IV/PO q12h for 6 weeks
Pediatric dose: Ceftriaxone 100 mg/kg/24h IV/IM once daily; Gentamicin 3 mg/kg/24h IV/IM q8h; Doxycycline 2–4 mg/kg/24h IV/PO q12h; Rifampin 20 mg/kg/24h PO/IV q12h

2.1.2 Documented Bartonella endocarditis

Preferred regimen: Doxycycline 200 mg/24h IV or PO q12h for 6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 2 weeks
Pediatric dose: Ceftriaxone 100 mg/kg/24h IV/IM once daily; Gentamicin 3 mg/kg/24h IV/IM q8h; Doxycycline 2–4 mg/kg/24h IV/PO q12h; Rifampin 20 mg/kg/24h PO/IV q12h

2.3. Enterococcus

2.3.1. Endocarditis caused by enterococcal strains susceptible to penicillin, gentamicin, and vancomycin

Preferred regimen : Ampicillin 12 g/24h IV q4h for 4–6 weeks OR Penicillin G 18–30 million U/24h IV either continuously or q4h for 4–6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 4–6 weeks
Alternative regimen : Vancomycin 30 mg/kg/24h IV q12h for 6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 6 weeks
Pediatric dose: Vancomycin 40 mg/kg/24h IV q8–12h; Gentamicin 3 mg/kg/24h IV/IM q8h

2.3.2. Endocarditis caused by enterococcal strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin

Preferred regimen : Ampicillin 12 g/24h IV q4h for 4–6 weeks OR Penicillin G 24 million U/24h IV continuously or q4h for 4–6 weeks AND Streptomycin 15 mg/kg/24h IV/IM q12h for 4–6 weeks
Alternative regimen : Vancomycin 30 mg/kg/24h IV q12h for 6 weeks AND Streptomycin 15 mg/kg/24h IV/IM q12h for 6 weeks
Pediatric dose: Ampicillin 300 mg/kg/24h IV q4–6h; Penicillin 300 000 U/kg/24h IV q4–6h; Streptomycin 20–30 mg/kg/24h IV/IM q12h; Vancomycin 40 mg/kg/24h IV q8–12h; Streptomycin 20–30 mg/kg/24h IV/IM q12h

2.3.3. Endocarditis caused by enterococcal strains resistant to penicillin and susceptible to aminoglycoside and vancomycin

β-Lactamase–producing strain

Preferred regimen: Ampicillin-sulbactam 12 g/24h IV q6h for 6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 6 weeks
Alternative regimen : Vancomycin 30 mg/kg/24h IV q12h for 6 weeks
Pediatric dose: Ampicillin-sulbactam 300 mg/kg/24h IV q6h; Gentamicin 3 mg/kg/24h IV/IM q8h

Intrinsic penicillin resistance

Preferred regimen: Vancomycin 30 mg/kg/24h IV q12h for 6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8h for 6 weeks
Pediatric dose: Vancomycin 40 mg/kg/24h IV q8–12h; Gentamicin 3 mg/kg/24h IV/IM q8h

2.3.4. Endocarditis caused by enterococcal strains resistant to penicillin, gentamicin, and vancomycin

Enterococcus faecium

Preferred regimen : Linezolid 1200 mg/24h IV/PO q12h for ≥ 8 weeks OR Quinupristin-Dalfopristin 22.5 mg/kg/24h IV q8h for 8 weeks

Enterococcus faecalis

Preferred regimen : Imipenem/cilastatin 2 g/24h IV q6h for ≥ 8 weeks AND Ampicillin 12 g/24h IV q4h for ≥ 8 weeks OR Ceftriaxone sodium 4 g/24h IV/IM q12h for ≥ 8 weeks AND Ampicillin 12 g/24h IV q4h for ≥ 8 weeks
Pediatric dose: Linezolid 30 mg/kg/24h IV/PO q8h; Quinupristin-Dalfopristin 22.5 mg/kg/24h IV q8h; Imipenem/cilastatin 60–100 mg/kg/24h IV q6h; Ampicillin 300 mg/kg/24h IV q4–6h; Ceftriaxone 100 mg/kg/24h IV/IM q12h

2.4. HACEK organisms

2.4.1. Endocarditis caused by Haemophilus, Aggregatibacter (Actinobacillus), Cardiobacterium, Eikenella corrodens, or Kingella

Preferred regimen : Ceftriaxone sodium 2 g/24h IV/IM in 1 dose for 4 weeks OR Ampicillin 12 g/24h IV q6h for 4 weeks OR Ciprofloxacin 1000 mg/24h PO or 800 mg/24h IV q12h for 4 weeks
Pediatric dose: Ceftriaxone 100 mg/kg/24h IV/IM once daily; Ampicillin-sulbactam 300 mg/kg/24h IV divided into 4 or 6 equally divided doses; Ciprofloxacin 20–30 mg/kg/24h IV/PO q12h

2.5. Staphylococcus

2.5.1. Native valve endocarditis caused by oxacillin-susceptible staphylococci

Preferred regimen (1): Nafcillin or Oxacillin 12 g/24h IV q4–6h for 6 weeks ± Gentamicin 3 mg/kg/24h IV/IM q8–12h for 3–5 days
Preferred regimen (2): Cefazolin 6 g/24h IV q8h for 6 weeks ± Gentamicin 3 mg/kg/24h IV/IM q8–12h for 3–5 days
Pediatric dose: Nafcillin or Oxacillin 200 mg/kg/24h IV q4–6h; Gentamicin 3 mg/kg/24h IV/IM q8h; Cefazolin 100 mg/kg/24h IV q8h; Gentamicin 3 mg/kg/24h IV/IM q8h

2.5.2. Native valve endocarditis caused by oxacillin-resistant staphylococci

Preferred regimen: Vancomycin 30 mg/kg/24h IV q12h for 6 weeks
Pediatric dose: Vancomycin 40 mg/kg/24h IV q8–12h

2.5.3. Prosthetic valve endocarditis caused by oxacillin-susceptible staphylococci

Preferred regimen: Nafcillin or Oxacillin 12 g/24h IV q4h for ≥ 6 weeks AND Rifampin 900 mg/24h IV/PO q8h for ≥ 6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8–12h for 2 weeks
Pediatric dose: Nafcillin or Oxacillin 200 mg/kg/24h IV q4–6h; Rifampin 20 mg/kg/24h IV/PO q8h; Gentamicin 3 mg/kg/24h IV/IM q8h

2.5.4 Prosthetic valve endocarditis caused by oxacillin-resistant staphylococci

Preferred regimen: Vancomycin 30 mg/kg 24 h q12h for ≥ 6 weeks AND Rifampin 900 mg/24h IV/PO q8h for ≥ 6 weeks AND Gentamicin 3 mg/kg/24h IV/IM q8–12h for 2 weeks
Pediatric dose: Vancomycin 40 mg/kg/24h IV q8–12h; Rifampin 20 mg/kg/24h IV/PO q8h (up to adult dose); Gentamicin 3 mg/kg/24h IV or IM q8h

2.6 Viridans group streptococci and Streptococcus bovis

2.6.1. Native valve endocarditis caused by highly penicillin-susceptible viridans group streptococci and Streptococcus bovis (MIC ≤ 0.12 μg/mL)

Preferred regimen: Penicillin G 12–18 million U/24h IV either continuously or q4–6h for 4 weeks OR Ceftriaxone 2 g/24h IV/IM in 1 dose for 4 weeks
Alternative regimen (1): (Penicillin G 12–18 million U/24h IV either continuously or q4h for 2 weeks OR Ceftriaxone 2 g/24h IV/IM in 1 dose for 2 weeks) AND Gentamicin 3 mg/kg/24h IV/IM in 1 dose for 2 weeks
Alternative regimen (2): Vancomycin 30 mg/kg/24h IV q12h not to exceed 2 g/24h for 4 weeks
Pediatric dose: Penicillin G 200,000 U/kg/24h IV q4–6h; Ceftriaxone 100 mg/kg/24h IV/IM in 1 dose; Gentamicin 3 mg/kg/24h IV/IM in 1 dose or q8h; Vancomycin 40 mg/kg/24h IV q8–12h

2.6.2. Native valve endocarditis caused by relatively penicillin-resistant viridans group streptococci and Streptococcus bovis (MIC > 0.12 to ≤ 0.5 μg/mL)

Preferred regimen (1): (Penicillin G 24 million U/24h IV either continuously or q4–6h for 4 weeks OR Ceftriaxone 2 g/24h IV/IM in 1 dose for 4 weeks) AND Gentamicin 3 mg/kg/24h IV/IM in 1 dose for 2 weeks
Preferred regimen (2): Vancomycin 30 mg/kg/24h IV q12h not to exceed 2 g/24h for 4 weeks
Pediatric dose: Penicillin G 200,000 U/kg/24h IV q4–6h; Ceftriaxone 100 mg/kg/24h IV/IM in 1 dose; Gentamicin 3 mg/kg/24h IV/IM in 1 dose or q8h; Vancomycin 40 mg/kg/24h IV q8–12h

2.6.3. Prosthetic valve endocarditis caused by highly penicillin-susceptible viridans group streptococci and Streptococcus bovis (MIC ≤ 0.12 μg/mL)

Preferred regimen (1): (Penicillin G 24 million U/24h IV either continuously or q4–6h for 6 weeks OR Ceftriaxone 2 g/24h IV/IM in 1 dose for 6 weeks) ± Gentamicin 3 mg/kg/24h IV/IM in 1 dose for 2 weeks
Preferred regimen (2): Vancomycin 30 mg/kg/24h IV q12h not to exceed 2 g/24h for 6 weeks
Pediatric dose: Penicillin G 200,000 U/kg/24h IV q4–6h; Ceftriaxone 100 mg/kg/24h IV/IM in 1 dose; Gentamicin 3 mg/kg/24h IV/IM in 1 dose or q8h; Vancomycin 40 mg/kg/24h IV q8–12h

2.6.4. Prosthetic valve endocarditis caused by relatively penicillin-resistant viridans group streptococci and Streptococcus bovis (MIC > 0.12 μg/mL)

Preferred regimen (1): (Penicillin G 24 million U/24h IV either continuously or q4–6h for 6 weeks OR Ceftriaxone 2 g/24h IV/IM in 1 dose for 6 weeks) AND Gentamicin 3 mg/kg/24h IV/IM in 1 dose for 2 weeks
Preferred regimen (2): Vancomycin 30 mg/kg/24h IV q12h not to exceed 2 g/24h for 6 weeks
Pediatric dose: Penicillin G 200,000 U/kg/24h IV q4–6h; Ceftriaxone 100 mg/kg/24h IV/IM in 1 dose; Gentamicin 3 mg/kg/24h IV/IM in 1 dose or q8h; Vancomycin 40 mg/kg/24h IV q8–12h

Antithrombotic Therapy

Anticoagulants can cause or worsen hemorrhage in patients with endocarditis but maybe carefully administered when needed.^[4]
The prothrombin time should be carefully maintained at an INR of 2.0–3.0.
Anticoagulation should be reversed immediately in the event of CNS complications and interrupted for 1–2 weeks after an acute embolic stroke.
Avoid heparin administration during active endocarditis if possible.

Class I
"1. Penicillin G or Amoxicilline or Ceftriaxonef(Level of Evidence: A)"
”2. (Paste guideline here) (Level of Evidence: C)"
”3. (Paste guideline here) (Level of Evidence: B)"

References

↑ Braunwald, Eugene; Bonow, Robert O. (2012). Braunwald's heart disease : a textbook of cardiovascular medicin. Philadelphia: Saunders. ISBN 978-1-4377-2708-1.
↑ Baddour, LM.; Wilson, WR.; Bayer, AS.; Fowler, VG.; Bolger, AF.; Levison, ME.; Ferrieri, P.; Gerber, MA.; Tani, LY. (2005). "Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America". Circulation. 111 (23): e394–434. doi:10.1161/CIRCULATIONAHA.105.165564. PMID 15956145. Unknown parameter |month= ignored (help)
↑ Baddour, Larry M.; Wilson, Walter R.; Bayer, Arnold S.; Fowler, Vance G.; Bolger, Ann F.; Levison, Matthew E.; Ferrieri, Patricia; Gerber, Michael A.; Tani, Lloyd Y.; Gewitz, Michael H.; Tong, David C.; Steckelberg, James M.; Baltimore, Robert S.; Shulman, Stanford T.; Burns, Jane C.; Falace, Donald A.; Newburger, Jane W.; Pallasch, Thomas J.; Takahashi, Masato; Taubert, Kathryn A.; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease; Council on Cardiovascular Disease in the Young; Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia; American Heart Association; Infectious Diseases Society of America (2005-06-14). "Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America". Circulation. 111 (23): –394-434. doi:10.1161/CIRCULATIONAHA.105.165564. ISSN 1524-4539. PMID 15956145.
↑ Baddour Larry M., Wilson Walter R., Bayer Arnold S., Fowler Vance G. Jr, Bolger Ann F., Levison Matthew E., Ferrieri Patricia, Gerber Michael A., Tani Lloyd Y., Gewitz Michael H., Tong David C., Steckelberg James M., Baltimore Robert S., Shulman Stanford T., Burns Jane C., Falace Donald A., Newburger Jane W., Pallasch Thomas J., Takahashi Masato, Taubert Kathryn A. (2005). "Infective Endocarditis: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association-Executive Summary: Endorsed by the Infectious Diseases Society of America". Circulation. 111 (23): 3167–84. PMID 15956145.

[1] Braunwald, Eugene; Bonow, Robert O. (2012). Braunwald's heart disease : a textbook of cardiovascular medicin. Philadelphia: Saunders. ISBN 978-1-4377-2708-1.

[Baddour-2005-2] Baddour, LM.; Wilson, WR.; Bayer, AS.; Fowler, VG.; Bolger, AF.; Levison, ME.; Ferrieri, P.; Gerber, MA.; Tani, LY. (2005). "Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America". Circulation. 111 (23): e394–434. doi:10.1161/CIRCULATIONAHA.105.165564. PMID 15956145. Unknown parameter |month= ignored (help)

[3] Baddour, Larry M.; Wilson, Walter R.; Bayer, Arnold S.; Fowler, Vance G.; Bolger, Ann F.; Levison, Matthew E.; Ferrieri, Patricia; Gerber, Michael A.; Tani, Lloyd Y.; Gewitz, Michael H.; Tong, David C.; Steckelberg, James M.; Baltimore, Robert S.; Shulman, Stanford T.; Burns, Jane C.; Falace, Donald A.; Newburger, Jane W.; Pallasch, Thomas J.; Takahashi, Masato; Taubert, Kathryn A.; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease; Council on Cardiovascular Disease in the Young; Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia; American Heart Association; Infectious Diseases Society of America (2005-06-14). "Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America". Circulation. 111 (23): –394-434. doi:10.1161/CIRCULATIONAHA.105.165564. ISSN 1524-4539. PMID 15956145.

[Baddour-4] Baddour Larry M., Wilson Walter R., Bayer Arnold S., Fowler Vance G. Jr, Bolger Ann F., Levison Matthew E., Ferrieri Patricia, Gerber Michael A., Tani Lloyd Y., Gewitz Michael H., Tong David C., Steckelberg James M., Baltimore Robert S., Shulman Stanford T., Burns Jane C., Falace Donald A., Newburger Jane W., Pallasch Thomas J., Takahashi Masato, Taubert Kathryn A. (2005). "Infective Endocarditis: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association-Executive Summary: Endorsed by the Infectious Diseases Society of America". Circulation. 111 (23): 3167–84. PMID 15956145.

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