Endocarditis medical therapy: Difference between revisions

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Revision as of 18:44, 12 August 2015

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

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).

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.^[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.

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). ^[2]

Treatment

Antimicrobial Regimen

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/24h 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/24h 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

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/24h 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/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/24h PO or 800 mg/24h IV q12h for 4–6 weeks AND Rifampin 900 mg/24h 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

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 4–6weeks
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

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.

[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.

[1]

[2]

[3]

@@ Line 31: / Line 31: @@
 * 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'''
+::* '''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/24h 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)'''
+::* '''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
 :::* 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
-::* '''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
 :::* 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
 :::* 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
 :::* 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
@@ Line 52: / Line 52: @@
 :* '''2. Pathogen-directed antimicrobial therapy'''
 ::* '''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
 ::::* 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
@@ Line 61: / Line 61: @@
 ::* '''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
 ::::* 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'''
+:::* '''2.3.2. 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'''
+:::* '''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
@@ Line 80: / Line 80: @@
 :::::* 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
 :::::* 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 87: @@
 :::::* 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
 ::::* 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 (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
-:::* '''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
 ::::* 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
 ::::* 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
 ::::* 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