1. Infective endocarditis Heart Disease Braunwald CV R4 李威廷醫師 Supervisor: 李貽恆醫師

2. Infective endocarditis Definition: Microbial infection of the endothelial surface Valves Septal defect chordae tendineae mural endothelium NVE: native valve endocarditis PVE: prosthetic valve endocarditis

3. Infective endocarditis Incidence: 2 / 100,000 patient-years, 15—30 / 100,000 patient-years ( >60 y/o) Rheumatic heart disease Congenital heart disease Mitral valve prolapse with regurgitation Degenerative heart disease Asymmetrical septal hypertrophy Intravenous drug abuse Prosthetic valve (7—25%)

5. Infective endocarditis: patient groups Children with IE: congenital heart disease (aortic valve), normal structure (tricuspid valve), Staphylococcus (neonate), Streptococcus group B (children), S. pneumonia (rare) Adults with IE: redundancy, thickened leaflets, >45 y/o MVP + MR: 52 / 100,000 patient-years Rheumatic heart disease: MV (F>M), AV (M>F) Congenital heart disease: PDA, VSD, bicuspid AV

6. Infective endocarditis: patient groups IV drug abusers with IE: 5.3—6400 / 100,000 patient-years, TV (46—78%)  MV (24—32%)  AV (8—19%) S. aureus, GNB (Pseudomonas), polymicrobial S/S: pleuritic chest pain, SOB, cough, hemoptysis, HIV: 73%; increased mortality (CD4 < 200) Prosthetic valves with IE: greater incidence post 6-month valvular surgery early (< 60 days) : surgical complication, late (> 60 days): community or nosocomial ring abscess, annular invasion, paravalvular regurgitation

7. Infective endocarditis: nosocomial Infected intracardiac device and catheter GI or GU tract surgery or instrumentation High mortality (40—56%) GPC ( S. aureus, CONS, Enterococcus) S. aureus catheter related bacteremia (23%) : TEE

8. Infective endocarditis: microorganism Streptococcus viridans: 35 — 65% NVE normal inhabitants of the oropharynx penicillin sensitive penicillin plus aminoglycoside S. bovis : colon polyp or malignancy Group A streptococcus : drug abuser, tricuspid valve Group B streptococcus : systemic emboli Group G streptococcus :

9. Infective endocarditis: microorganism Streptococcus pneumoniae: alcoholism aortic valve concurrent pneumonia or meningitis Penicillin / Rocephin  Vancomycin Enterococcus: normal GI tract flora and cause GU infection 5—15% NVE and PVE resistant to Oxacillin Penicillin / Ampicillin / Vancomycin / Teicoplanin + GM

10. Infective endocarditis: microorganism Staphylococcus: Coagulase-positive: S. aureus highly toxic febrile 30—50% CNS involvement Mortality: 16—46% (L’t), 2—4% (R’t) Oxacillin / 1 st cephalosporin Coagulase-negative: S epidermidis Major cause of PVE community-acquired: Oxacillin sensitive nosocomial infection: Oxacillin resistant

11. Infective endocarditis: microorganism Gram negative bacteria: upper respiratory tract and oropharyngeal flora B/C incubation 3 weeks P. aeruginosa: most common in GNB IE HACEK: haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae Fungus: drug abuser and post valve replacement common: C. albicans (PVE); C. parapsilosis (NVE)

12. Infective endocarditis: pathogenesis Vascular endothelial reaction Hemostatic mechanism Host immune system Gross anatomic abnormalities Surface property of microorganism Initial bacteremia

13. Infective endocarditis: pathogenesis Nonbacterial thrombotic endocarditis (NBTE) Malignancy, DIC, uremia, burn, SLE, valvular heart disease, and intracardiac catheter Atrial side of MV/ TV, and ventricular side of AV/ PV: (1) high velocity jet (2) flow from a high to a low pressure chamber (3) flow across a narrow orifice (Venturi’s effect) Infective endocarditis (IE) specific mucosal surfaces and skin, density of colonizing bacteria, and the extent of local trauma, esp. oral mucosa Dextran (streptococcus), fibronectin (S. aureus, S. viridans)

14. Infective endocarditis: pathophysiology Local destruction of intracardiac infection: valve, chordae tendineae, fistula, paravalvular abscess, conduction Distant embolization with infarct or infection: 45—65% (autopsy), 70% pulmonary embolism in R’t IE Hematogenous seeding with bacteremia: metasttic infection, Immune-complex or antibody reaction: IgM, IgA, IgG, Osler’s node, Rheumatoid factor, Roth’s spot

15. Infective endocarditis: clinic Fever: most common Heat murmur: 80—85% CHF : valve destruction, chordae tendon rupture, intracardic fistula Enlargement of spleen: 15—50% Petechiae: most common peripheral sign Splinter or subungual homorrhages, Osler’s nodes, Janeway’s lesions, Roth’s spots

16. Infective endocarditis: clinic Myalgia, arthralgia, back pain Systemic emboli Neurological: 30—40%, embolic stroke (most common), mycotic aneurysm, Renal insufficiency: imm8une-complex mediated glomerulonephritis (azotemia); embolic renal infarct (hematuria)

18. Infective endocarditis: diagnosis Duke criteria: Major criteria: B/C, echogram Minor criteria: predisposition, fever vascular phenomenon, microbiological evidence, echogram TEE (sensitivity: 82—94%)

20. Infective endocarditis: diagnosis Anemia : normochromic, low Fe, low TIBC Leukocytosis ESR (erythrocyte sedmentation rate): elevation except in congestive heart failure, renal failure and DIC Thrombocytopenia: rare CRP, RF, immune complex, cryoprotein U/A: protenuria and microscopic hematuria (50%)

21. Infective endocarditis: diagnosis Echocardiography should not be used as a screening test for IE in unselective patients with positive blood cultures or in patients with fever of unknown origins when clinical probability is low Echocardiography should be performed in all patients with clinically suspected IC, including those with negative blood cultures TEE: diagnosis, IE complication and follow up TEE: sensitivity ( 82—94%) both in NVE and PVE TTE: sensitivity ( <65%); specificity ( = 100%) in NVE sensitivity (16—36%) in PVE Thickened valve, ruptured valve or chordae, calcification, nodules

22. Infective endocarditis: treatment Eradication 10 9 to 10 10 organisms per gram of tissue Bactericidal, parenteral MIC: minimum inhibition concentration MBC: minimum bactericidal concentration Tolerance: MBC > 10x MIC Synergy

23. Infective endocarditis: treatment Streptococcus viridans or bovis in NVE penicillin sensitive: Aq penicillin 2-3MU q4h x4wks or Rocephin 2g qd x4wks or Vancomycin 15mg/kg q12h x4wks or (Aq + GM 1mg/kg q8h) x2wks (uncomplicated condition) Streptococcus viridans or bovis in PVE Aq penicillin 2-3MU q4h x6wks plus GM 1mg/kg q8h x2wks

24. Infective endocarditis: treatment Streptococcus viridans or bovis in NVE penicillin resistant (MIC= 0.2—0.5) Aq penicillin 3MU q4h x4wks or Rocephin 2g qd x4wks or Vancomycin 15mg/kg q12h x4wks plus GM 1mg/kg q8h x2wks penicillin resistant (MIC >0.5): as enterococcus protocol

25. Infective endocarditis: treatment S. pyogens, pneumoniae, group B, C, G penicillin sensitive: Aq penicillin 3MU q4h x4wks GM 1mg/kg q8h x2wks before MIC & penicillin resistant (MIC >0.1): Rocephin 2g qd + Vancomycin 15mg/kg q12h x4wks GM 1mg/kg q8h x2wks early surgery for cardiac complications

26. Infective endocarditis: treatment Enterococcus Aq penicillin 3-5MU q4h x4-6wks or Ampicillin 2g q4h x4-6wks or Vancomycin 15mg/kg q12h x4-6wks plus GM 1mg/kg q8h x4-6wks Gentamicin resistant, prevent nephrotoxicity, ototoxicity Cephalosporin is not alternative therapy Early surgery if high resistant to Penicillin / Ampicillin / Vancomycin

27. Infective endocarditis: treatment Staphylococcus with NVE OSSA: Oxacillin 2g q4h x4-6 wks (2wks *) or Cefazolin 2g q8h x4-6wks plus GM 1mg/kg q8h x3-5 days or Vancomycin 15mg/kg q12h x4-6wks ORSA: Vancomycin 15mg/kg q12h x4-6wks

28. Infective endocarditis: treatment Staphylococcus with PVE OSSA: Oxacillin 2g q4h >=6wks plus Rifampin 300mg po q8h >=6wks plus GM 1mg/kg q8h x2wks ORSA: Vancomycin 15mg/kg q12h x4-6wks plus Rifampin plus GM

29. Infective endocarditis: treatment HACEK group: Rocephin 2g qd x4wks or Ampicillin 2g q4h x4wks plus GM 1mg/kg q8h x4wks Pseudomonas aeruginosa: Ticarcillin / Piperacillin plus GM

30. Infective endocarditis: treatment Culture-negative NVE Ampicillin 2g q4h x4-6wks or Rocephin 2g qd x4-6wks plus GM 1mg/kg q8h x4-6 wks Culture-negative PVE Ampicillin / Rocephin + GM plus Vancomycin 15mg/kg q12h x4-6wks

31. Infective endocarditis: treatment Outpatient: response to initial therapy and free of fever not experiencing threatening complications good drug compliance general condition evaluation Monitor treatment: 33% adverse effect of beta-lactam patients, (Oxacillin and Ampicillin) fever, rash, neutropenia, mean =15 days

32. Infective endocarditis Extracardiac complications Splenic abscess: percutaneous needle aspiration for diagnosis drainage for successful treatment Mycotic aneurysm and septic arteritis: cerebral cortex, middle cerebral artery branches septic embolite with secondary arteritis: S. aureus bacterial seeding: Streptococcus viridans

34. Infective endocarditis: prevention NBTE  X IE Streptococcus viridans: esophagus, respiratory tract, oral mucosa Enterococcus: GI and GU tract Staphylococcus aureus: skin Retrospective study, cost-benefit 55-75% patients did not know cardiac lesion till IE 5% IE patients knew cardiac lesion and recent procedure with prophylaxis penicillin-resistant bacteria due to other antibiotics prophylaxis

38. Infective endocarditis prevention High risk procedure: Dental: high- and moderate- risk group Non-dental : high risk group MVP without murmur: not prophylaxis, but risk slightly increase

39. IE prophylaxis High risk: normal population: (pre-30 min) Ampicillin 2g IV/IM + GM 1.5mg/kg (post-6 hour) Ampicillin 1g IV/IM or Amoxicillin 1g po penicillin allergy: (pre-30 min) Vancomycin 1g IVD + GM 1.5mg/kg (post-6 hour) no second dose

40. IE prophylaxis Moderate risk: normal population: (pre-1 hour) Amoxicillin 2g po or (pre-30 min) Ampicillin 2g IV/IM penicillin allergy: (pre-30 min) Vancomycin 1g IVD (post-6 hour) no second dose