Endocarditis medical therapy: Difference between revisions

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{{Endocarditis}}
{{Endocarditis}}


{{CMG}}; {{AE}} {{CZ}}; {{AZ}}; {{MM}}
{{CMG}}; '''Associate Editors-in-Chief:''' {{CZ}}


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


==Timing of Initiation of Antibiotics==
==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 culture]]s, as this delay allows an additional blood cultures without the confounding effect of [[Empirical|empiric]] treatment, which is very important in determining the causing [[pathogens]].<ref>{{Cite book  | last1 = Braunwald | first1 = Eugene | last2 = Bonow | first2 = Robert O. | title = Braunwald's heart disease : a textbook of cardiovascular medicin | date = 2012 | publisher = Saunders | location = Philadelphia | isbn = 978-1-4377-2708-1 | pages =  }}</ref>
* 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]]). <ref name="Baddour-2005">{{Cite journal  | last1 = Baddour | first1 = LM. | last2 = Wilson | first2 = WR. | last3 = Bayer | first3 = AS. | last4 = Fowler | first4 = VG. | last5 = Bolger | first5 = AF. | last6 = Levison | first6 = ME. | last7 = Ferrieri | first7 = P. | last8 = Gerber | first8 = MA. | last9 = Tani | first9 = LY. | title = 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. | journal = Circulation | volume = 111 | issue = 23 | pages = e394-434 | month = Jun | year = 2005 | doi = 10.1161/CIRCULATIONAHA.105.165564 | PMID = 15956145 }}</ref>


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.
===Timing of Initiation of Antibiotics===


==Duration of Antibiotic Therapy==
* [[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.


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.
===Duration of Antibiotic Therapy===


==Empirical 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.


* Antibiotic therapy for subacute hemodynamically stable disease, and in those who have received antibiotics recently can be delayed waiting for the results of [[blood culture]]s, as this delay allows an additional blood cultures without the confounding effect of empiric treatment, which is very important in determining the causing pathogens.<ref>{{Cite book  | last1 = Braunwald | first1 = Eugene | last2 = Bonow | first2 = Robert O. | title = Braunwald's heart disease : a textbook of cardiovascular medicin | date = 2012 | publisher = Saunders | location = Philadelphia | isbn = 978-1-4377-2708-1 | pages = }}</ref>
===Antimicrobial Regimens===
*[[Infective endocarditis]]<ref>{{Cite journal| doi = 10.1161/CIRCULATIONAHA.105.165564| issn = 1524-4539| volume = 111| issue = 23| pages = –394-434| last1 = Baddour| first1 = Larry M.| last2 = Wilson| first2 = Walter R.| last3 = Bayer| first3 = Arnold S.| last4 = Fowler| first4 = Vance G.| last5 = Bolger| first5 = Ann F.| last6 = Levison| first6 = Matthew E.| last7 = Ferrieri| first7 = Patricia| last8 = Gerber| first8 = Michael A.| last9 = Tani| first9 = Lloyd Y.| last10 = Gewitz| first10 = Michael H.| last11 = Tong| first11 = David C.| last12 = Steckelberg| first12 = James M.| last13 = Baltimore| first13 = Robert S.| last14 = Shulman| first14 = Stanford T.| last15 = Burns| first15 = Jane C.| last16 = Falace| first16 = Donald A.| last17 = Newburger| first17 = Jane W.| last18 = Pallasch| first18 = Thomas J.| last19 = Takahashi| first19 = Masato| last20 = Taubert| first20 = Kathryn A.| last21 = Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease| last22 = Council on Cardiovascular Disease in the Young| last23 = Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia| last24 = American Heart Association| last25 = Infectious Diseases Society of America| title = 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| journal = Circulation| date = 2005-06-14| pmid = 15956145}}</ref>


* 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.
:*'''1. Culture-negative endocarditis'''
 
::*'''1.1. Culture-negative, native valve endocarditis'''
* 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). <ref name="Baddour-2005">{{Cite journal  | last1 = Baddour | first1 = LM. | last2 = Wilson | first2 = WR. | last3 = Bayer | first3 = AS. | last4 = Fowler | first4 = VG. | last5 = Bolger | first5 = AF. | last6 = Levison | first6 = ME. | last7 = Ferrieri | first7 = P. | last8 = Gerber | first8 = MA. | last9 = Tani | first9 = LY. | title = 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. | journal = Circulation | volume = 111 | issue = 23 | pages = e394-434 | month = Jun | year = 2005 | doi = 10.1161/CIRCULATIONAHA.105.165564 | PMID = 15956145 }}</ref>
 
==Treatment==
===Antimicrobial Regimen===
* Infective endocarditis<ref>{{Cite journal| doi = 10.1161/CIRCULATIONAHA.105.165564| issn = 1524-4539| volume = 111| issue = 23| pages = –394-434| last1 = Baddour| first1 = Larry M.| last2 = Wilson| first2 = Walter R.| last3 = Bayer| first3 = Arnold S.| last4 = Fowler| first4 = Vance G.| last5 = Bolger| first5 = Ann F.| last6 = Levison| first6 = Matthew E.| last7 = Ferrieri| first7 = Patricia| last8 = Gerber| first8 = Michael A.| last9 = Tani| first9 = Lloyd Y.| last10 = Gewitz| first10 = Michael H.| last11 = Tong| first11 = David C.| last12 = Steckelberg| first12 = James M.| last13 = Baltimore| first13 = Robert S.| last14 = Shulman| first14 = Stanford T.| last15 = Burns| first15 = Jane C.| last16 = Falace| first16 = Donald A.| last17 = Newburger| first17 = Jane W.| last18 = Pallasch| first18 = Thomas J.| last19 = Takahashi| first19 = Masato| last20 = Taubert| first20 = Kathryn A.| last21 = Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease| last22 = Council on Cardiovascular Disease in the Young| last23 = Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia| last24 = American Heart Association| last25 = Infectious Diseases Society of America| title = 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| journal = Circulation| date = 2005-06-14| pmid = 15956145}}</ref>
:* '''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
:::* 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/24h PO or 800 mg/24h IV q12h 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
:::* 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)'''
::*'''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/24h PO/IV q8h for 6 weeks
:::* 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/24h PO/IV q8h
:::* 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)'''
::*'''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
:::* 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/24h PO or 800 mg/24h IV q12h 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
:::* 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)'''
::*'''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/24h PO/IV q8h for 6 weeks
:::* 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/24h PO or 800 mg/24h IV q12h for 4–6 weeks {{and}} [[Rifampin]] 900 mg/24h 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/24h PO/IV q8h
:::* 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. Pathogen-directed antimicrobial therapy'''
::* '''2.1. Bartonella'''
::* '''2.1. Bartonella'''
:::* '''2.1.1 Suspected Bartonella endocarditis'''
:::* '''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 {{withorwithout}} [[Doxycycline]] 200 mg/kg/24h IV/PO q12h for 6 weeks
::::* 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 {{withorwithout}} [[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
::::* 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
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::::* 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
::::* 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. Enterococcus'''
:::* '''2.3.1 Endocarditis caused by enterococcal strains susceptible to penicillin, gentamicin, and vancomycin'''
:::*'''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 4–6weeks
::::* 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
::::* 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
::::* 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'''
:::* '''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
::::* 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
::::* 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
::::* 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'''
:::* '''2.3.3. Endocarditis caused by enterococcal strains resistant to penicillin and susceptible to aminoglycoside and vancomycin'''
::::* β-Lactamase–producing strain
::::* 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
:::::* Preferred regimen: [[Ampicillin-sulbactam]] 12 g/24h IV q6h for 6 weeks {{and}} [[Gentamicin]] 3 mg/kg/24h IV/IM q8h for 6 weeks
Line 80: Line 78:
:::::* Pediatric dose: [[Vancomycin]] 40 mg/kg/24h IV q8–12h; [[Gentamicin]] 3 mg/kg/24h IV/IM q8h
:::::* 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'''
:::* '''2.3.4. Endocarditis caused by enterococcal strains resistant to penicillin, gentamicin, and vancomycin'''
::::* Enterococcus faecium
::::* 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
:::::* 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
Line 87: Line 85:
:::::* 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
:::::* 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. HACEK organisms'''
:::* '''Endocarditis caused by Haemophilus, Aggregatibacter (Actinobacillus), Cardiobacterium, Eikenella corrodens, or Kingella'''
:::* '''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
::::* 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
::::* 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. Staphylococcus'''
:::* '''Native valve endocarditis caused by oxacillin-susceptible staphylococci'''
:::* '''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 {{withorwithout}} [[Gentamicin]] 3 mg/kg/24h IV/IM q8–12h for 3–5 days
::::* Preferred regimen (1): [[Nafcillin]] or [[Oxacillin]] 12 g/24h IV q4–6h for 6 weeks {{withorwithout}} [[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 {{withorwithout}} [[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 {{withorwithout}} [[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
::::* 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


:::* '''Native valve endocarditis caused by oxacillin-resistant staphylococci'''
:::* '''2.5.2. Native valve endocarditis caused by oxacillin-resistant staphylococci'''
::::* Preferred regimen: [[Vancomycin]] 30 mg/kg/24h IV q12h for 6 weeks
::::* Preferred regimen: [[Vancomycin]] 30 mg/kg/24h IV q12h for 6 weeks
::::* Pediatric dose: [[Vancomycin]] 40 mg/kg/24h IV q8–12h
::::* Pediatric dose: [[Vancomycin]] 40 mg/kg/24h IV q8–12h


:::* '''Prosthetic valve endocarditis caused by oxacillin-susceptible staphylococci'''
:::* '''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
::::* 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
::::* 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


:::* '''Prosthetic valve endocarditis caused by oxacillin-resistant staphylococci'''
:::* '''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
::::* 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
::::* 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
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::::* Preferred regimen (2): [[Vancomycin]] 30 mg/kg/24h IV q12h not to exceed 2 g/24h for 6 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
::::* 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==
*[[Anticoagulant]]s can cause or worsen [[hemorrhage]] in patients with [[endocarditis]] but maybe carefully administered when needed.<ref name="Baddour">{{cite journal | author = 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.| title = 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. | journal = Circulation | volume = 111 | issue = 23 | pages = 3167-84 | year = 2005 | id = PMID 15956145 }}</ref>
* 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="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen" |[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
| bgcolor="LightGreen" |
|-
| bgcolor="LightGreen" |"'''1.'''  Penicillin G or Amoxicilline or Ceftriaxonef''([[ACC AHA guidelines classification  scheme#Level of Evidence|Level of Evidence:  A]])''"
| bgcolor="LightGreen" |
|-
| bgcolor="LightGreen" |”'''2.'''  (Paste guideline here) ''([[ACC AHA guidelines classification  scheme#Level of Evidence|Level of Evidence:  C]])''"
| bgcolor="LightGreen" |
|-
| bgcolor="LightGreen" |”'''3.'''  (Paste guideline here) ''([[ACC AHA guidelines classification  scheme#Level of Evidence|Level of Evidence:  B]])''"
| bgcolor="LightGreen" |
|}


==References==
==References==
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[[Category:Emergency medicine]]
[[Category:Emergency medicine]]
[[Category:Cardiology]]
[[Category:Cardiology]]
[[Category:Infectious disease]]
 
[[Category:Intensive care medicine]]
[[Category:Intensive care medicine]]
[[Category:Up-To-Date]]
[[Category:Up-To-Date]]
[[Category: Infectious Disease Project]]

Latest revision as of 22:48, 5 March 2020

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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

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

  • 1. Culture-negative endocarditis
  • 1.1. Culture-negative, native valve endocarditis
  • 1.2. Culture-negative, prosthetic valve endocarditis (early, ≤ 1 year)
  • 1.3. Culture-negative, prosthetic valve endocarditis (late, > 1 year)
  • 1.4. Culture-negative, prosthetic valve endocarditis (early, ≤ 1 year)
  • 2. Pathogen-directed antimicrobial therapy
  • 2.1. Bartonella
  • 2.1.1. Suspected Bartonella endocarditis
  • 2.1.2 Documented Bartonella endocarditis
  • 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
  • 2.3.3. Endocarditis caused by enterococcal strains resistant to penicillin and susceptible to aminoglycoside and vancomycin
  • β-Lactamase–producing strain
  • Intrinsic penicillin resistance
  • 2.3.4. Endocarditis caused by enterococcal strains resistant to penicillin, gentamicin, and vancomycin
  • Enterococcus faecium
  • Enterococcus faecalis
  • 2.4. HACEK organisms
  • 2.4.1. Endocarditis caused by Haemophilus, Aggregatibacter (Actinobacillus), Cardiobacterium, Eikenella corrodens, or Kingella
  • 2.5. Staphylococcus
  • 2.5.1. Native valve endocarditis caused by oxacillin-susceptible staphylococci
  • 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
  • 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


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

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