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  • NBTE: nonbacterial thrombotic endocarditis ; PVE: prosthetic vaive encardoditus
  • Actinobacillus : 放线杆菌属 ; Cardiobacterium : 心杆菌属 ; Eikenella : 埃肯菌属 ; Kingella : 金氏杆菌属
  • MIC: minimal inhibitory concentration ; MBC: minimal bactericidal concentration
  • I&D : i ncision and drainag e
  • Torulopsis : 球拟酵母菌属 ; Aspergillus : 曲霉
  • ET: endotracheal
  • 15 ie

    1. 1. Infective Endocarditis Weiyi Mai M.D. & Ph.D. Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University
    2. 2. Introduction <ul><li>Infective endocarditis (IE) is a disease that produces vegetations on the endocardium. </li></ul><ul><li>A heart valve or endothelium of adjacent large artery is usually involved . </li></ul><ul><li>Two major predisposing causes are : a susceptible cardiovascular substrate and a source of bacteremia . Majority of cases caused by streptococcus, staphylococcus, enterococcus, or fastidious gram negative cocco-bacillary forms. </li></ul>
    3. 3. Microbiology sx’s<60 d post op
    4. 4. Classification <ul><li>Progression: </li></ul><ul><ul><li>Acute: days-6 wks, Staphylococcus aureus </li></ul></ul><ul><ul><li>Subacute: 6wks-1yr, Viridans streptococci </li></ul></ul><ul><li>Valve: </li></ul><ul><ul><li>Native : 75% Viridans streptococci, 6% Enterococci… </li></ul></ul><ul><ul><li>Prosthetic : 50% S. epidermidis & aureus , G-& fungi </li></ul></ul><ul><ul><li>Iv drug abusers : 50% S. aureus , 20% streptococci & enterococci, 6% G- & 6% fungi </li></ul></ul>
    5. 5. Epidemiology <ul><li>Exact incidence difficult to measure. </li></ul><ul><ul><li>Estimated at 0.16 - 5.4 cases/1000 admissions. </li></ul></ul><ul><ul><li>Is increasing as the at-risk population grows. </li></ul></ul><ul><li>Age distribution is changing. </li></ul><ul><ul><li>mean age of patient is up to 55 years. </li></ul></ul><ul><li>Male:Female = 2-9:1 </li></ul><ul><li>Uncommon in pregnancy </li></ul>
    6. 6. Epidemiology( cont.) <ul><li>Severe kidney disease </li></ul><ul><li>Diabetes </li></ul><ul><li>IVs or skin disease </li></ul><ul><ul><li>(skin flora) </li></ul></ul><ul><li>Flossing (borderline) </li></ul><ul><ul><li>(dental flora) </li></ul></ul>
    7. 7. Terminology: SBE, IE, ABE, NVE, NBTE, or PVE? <ul><li>“ Infectious endocarditis” now preferred… </li></ul><ul><ul><li>subacute vs. acute is arbitrary and antiquated. </li></ul></ul><ul><ul><li>etiology may be fungal, bacterial, possibly viral </li></ul></ul><ul><ul><li>“ Infectious” differentiates from marantic, verrucous, rheumatic, etc. </li></ul></ul>
    8. 8. HACEK organisms <ul><li>Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella </li></ul><ul><li>Gram negative inhabitants of the upper airways. </li></ul><ul><li>Large vegetations, high likelihood of embolization. </li></ul><ul><li>Slow growing: hold cultures for 3 weeks. </li></ul><ul><li>Traditionally sensitive to beta lactams, now some produce beta lactamase. </li></ul>
    9. 9. Pathogenesis Pathegenesis
    10. 10. Modes of endothelial injury <ul><ul><li>Lesions seen at coaptation points of valves </li></ul></ul><ul><ul><ul><li>Atrial surface: mitral/tricuspid </li></ul></ul></ul><ul><ul><ul><li>Ventricular surface: aortic/pulmonic </li></ul></ul></ul><ul><li>Mechanism </li></ul><ul><ul><ul><li>High velocity jet </li></ul></ul></ul><ul><ul><ul><li>Flow from high pressure to low pressure chamber </li></ul></ul></ul><ul><ul><ul><li>Flow across narrow orifice of high velocity </li></ul></ul></ul><ul><ul><li>Bacteria deposited on edges of low pressure sink or site of jet impaction </li></ul></ul>Venturi Effect
    11. 11. Venturi Effect
    12. 12. Pathology <ul><li>NVE infection is largely confined to leaflets </li></ul><ul><li>PVE infection commonly extends beyond valve ring into annulus/periannular tissue </li></ul><ul><li>Ring abscesses </li></ul><ul><ul><ul><li>Septal abscesses </li></ul></ul></ul><ul><ul><ul><li>Fistulae </li></ul></ul></ul><ul><ul><ul><li>Prosthetic dehiscence </li></ul></ul></ul><ul><li>Invasive infection more common in aortic position and if onset is early </li></ul>
    13. 13. Microscopy
    14. 14. Predisposing Factors <ul><li>Aged </li></ul><ul><ul><li>Degenerative valvular dz. </li></ul></ul><ul><ul><li>Increased exposure to nosocomial bacteremia </li></ul></ul><ul><ul><li>Prosthetic valves </li></ul></ul><ul><li>Gender (M>F) </li></ul><ul><li>Associated medical conditions : </li></ul><ul><ul><li>Long term HD </li></ul></ul><ul><ul><li>DM </li></ul></ul><ul><ul><li>Poor dental hygiene </li></ul></ul><ul><ul><li>HIV (independent) </li></ul></ul><ul><ul><li>Congenital defects </li></ul></ul><ul><ul><ul><li>MVP (100/100,000 p’t-yr, in advanced countries) </li></ul></ul></ul><ul><ul><ul><ul><li>MR </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Thickened leaflets </li></ul></ul></ul></ul><ul><ul><ul><li>ASD, VSD </li></ul></ul></ul><ul><ul><li>Injection-drug use (TV) </li></ul></ul><ul><ul><li>Long-term indwelling intravenous catheters </li></ul></ul><ul><ul><li>Rheumatic heart dz. (primarily the young in developing countries) </li></ul></ul>
    15. 15. Pathophysiology <ul><li>Clinical manifestations </li></ul><ul><ul><li>Direct </li></ul></ul><ul><ul><ul><li>Constitutional symptoms of infection (cytokine) </li></ul></ul></ul><ul><ul><li>Indirect </li></ul></ul><ul><ul><ul><li>Local destructive effects of infection </li></ul></ul></ul><ul><ul><ul><li>Embolization – septic or bland </li></ul></ul></ul><ul><ul><ul><li>Hematogenous seeding of infection </li></ul></ul></ul><ul><ul><ul><ul><ul><li>N.B. may present as local infection or persistent fever, metastatic abscesses may be small, miliary </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Immune response </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Immune complex or complement-mediated </li></ul></ul></ul></ul></ul>
    16. 16. Pathophysiology (cont.) <ul><li>Local destructive effects </li></ul><ul><ul><ul><li>Valvular distortion/destruction </li></ul></ul></ul><ul><ul><ul><li>Chordal rupture </li></ul></ul></ul><ul><ul><ul><li>Perforation/fistula formation </li></ul></ul></ul><ul><ul><ul><li>Paravalvular abscess </li></ul></ul></ul><ul><ul><ul><li>Conduction abnormalities </li></ul></ul></ul><ul><ul><ul><li>Purulent pericarditis </li></ul></ul></ul><ul><ul><ul><li>Functional valve obstruction </li></ul></ul></ul>
    17. 17. Pathophysiology(cont.2) <ul><li>Embolization </li></ul><ul><ul><ul><li>Clinically evident 11 – 43% of patients </li></ul></ul></ul><ul><ul><ul><li>Pathologically present 45 – 65% </li></ul></ul></ul><ul><ul><ul><li>High risk for embolization </li></ul></ul></ul><ul><ul><ul><ul><ul><li>Large > 10 mm vegetation </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Hypermobile vegetation </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Mitral vegetations (esp. anterior leaflet) </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Pulmonary (septic) – 65 – 75% of i.v. drug abusers with tricuspid IE </li></ul></ul></ul>
    18. 18. Clinical Features Symptoms % Signs % Fever 80-85 Fever 80-90 Chills 42-75 Murmur 80-85 Sweats 25 Changing/new murmur 10-40 Anorexia 25-55 Neurological abnormalities 30-40 Weight loss 25-35 Embolic events 20-40 malaise 25-40 Splenomegaly 15-50 dyspnia 20-40 Clubbing 10-20 Cough 25 Peripheral manifestation Stroke 13-20 Osler's nodes 7-10 Headache 15-40 Splinter hemorrhage 5-15 Nausea / vomiting 15-20 Petechiae 10-40 Myalgia / arthralgia 15-30 Janeway lesion 6-10 Chest pain 8-35 Retinal lesion/ Roth spot 4-10 Abdominal pain 5-15 Back pain 7-10 Confusion 10-20
    19. 19. AIE SIE Causative high virulence pyogenic bacteria: Staphylococcus aureus (50-80%) low virulence pyogenic bacteria: α-hemolytic streptococcus viridans (50-90%) Preexisting Cardiac abnormal usually no, Normal valves or prosthetic heart valves rheumatic valvular disease (50-60%), congenital heart disease (20%), ventricular septa defect (15%), normal valves 15%. Vegetation big, soft, friable pus-like , yellow-gray masses; white thrombus containing large amount of polymorphous neutrophils relatively firm, friable, irregular or polyp-like masses; white thrombus containing less amount of polymorphous neutrophils Valves change severe acute purulent valvulitis: the valves undergo erosion, perforation or rupture; granulation tissue is absent or scarce. mild chronic purulent valvulitis: fibrous thickening, perforation (less common), with granulation tissue in the base of the vegetation Chordae change break off very common fibrous thickened, shortened, break off less common Embolism Embolic abscesses Septicemia ( hepatomegaly, splenomegaly, hemorrhage of skin, mucosa, positive blood cultures ) Ischemic infarct (spleen, kidneys and brain)
    20. 20. ABE and SBE <ul><li>Acute </li></ul><ul><ul><li>Toxic presentation </li></ul></ul><ul><ul><li>Progressive valve destruction & metastatic infection developing in days to weeks </li></ul></ul><ul><ul><li>Most commonly caused by S. aureus </li></ul></ul><ul><li>Subacute </li></ul><ul><ul><li>Mild toxicity </li></ul></ul><ul><ul><li>Presentation over weeks to months </li></ul></ul><ul><ul><li>Rarely leads to metastatic infection </li></ul></ul><ul><ul><li>Most commonly S. viridans or enterococcus </li></ul></ul>
    21. 21. Peripheral Manifestations <ul><li>Janeway Lesions: </li></ul><ul><ul><li>erythematous, macular, non tender. </li></ul></ul><ul><ul><li>septic emboli? </li></ul></ul><ul><li>Osler’s Nodes: </li></ul><ul><ul><li>Tender, subcutaneous nodules. </li></ul></ul><ul><ul><li>4 P’s: </li></ul></ul><ul><ul><ul><li>Pink </li></ul></ul></ul><ul><ul><ul><li>Painful </li></ul></ul></ul><ul><ul><ul><li>Pea-sized </li></ul></ul></ul><ul><ul><ul><li>Pulp of the fingers/toes. </li></ul></ul></ul><ul><ul><li>Immunologic origin? </li></ul></ul>
    22. 22. Osler’s Node
    23. 23. Bleeding <ul><li>Subungual (splinter) hemorrhage </li></ul><ul><li>Conjunctival hemorrhage </li></ul><ul><li>Retinal hemorrhage: Roth Spot </li></ul>
    24. 24. Conjunctival Petechiae
    25. 25. Splinter Hemorrhage
    26. 26. Roth Spot
    27. 27. Clubbing
    28. 28. Lab Investigations <ul><li>Anemia of Chronic Disease in 50-80% </li></ul><ul><li>ESR “almost always” elevated. </li></ul><ul><ul><li>May be normal in those with CHF. </li></ul></ul><ul><li>Urinalysis </li></ul><ul><ul><li>gross or microscopic hematuria </li></ul></ul><ul><ul><li>casts in glomerulonephritis </li></ul></ul><ul><ul><li>bacteriuria and pyuria </li></ul></ul><ul><li>Elevated BUN and Creatinine </li></ul><ul><li>Rheumatoid factor present in 50% </li></ul>
    29. 29. Diagnosis <ul><li>Published criteria for diagnostic purposes in obscure cases </li></ul><ul><li>High index of suspicion in patients with predisposing anatomy or behavior </li></ul><ul><li>Blood cultures </li></ul><ul><li>Echocardiography </li></ul><ul><ul><li>TTE – 60% sensitivity </li></ul></ul><ul><ul><li>TEE – 80 – 95% sensitivity </li></ul></ul>
    30. 30. Diagnosis- Duke Criteria <ul><li>Major: </li></ul><ul><li>Persistently positive blood cultures </li></ul><ul><ul><li>Typical organisms for IE </li></ul></ul><ul><ul><li>Persistent bacteremia </li></ul></ul><ul><li>Evidence of endocardial involvement </li></ul><ul><ul><li>Positive ECHO </li></ul></ul><ul><ul><li>New valvular regurgitation </li></ul></ul>
    31. 31. Diagnosis- Duke Criteria (cont.) <ul><li>Minor: </li></ul><ul><li>Predisposing heart condition </li></ul><ul><li>Fever </li></ul><ul><li>Vascular phenomena </li></ul><ul><li>Immunologic phenomena </li></ul><ul><li>Positive BC (not meeting major) </li></ul><ul><li>Positive ECHO (not meeting major) </li></ul>
    32. 32. Diagnosis- Duke Criteria (cont.2) <ul><li>“ Definite”: </li></ul><ul><li>pathologic diagnosis </li></ul><ul><ul><li>Micro-organisms or </li></ul></ul><ul><ul><li>Pathologic lesion (confirmed by histology) </li></ul></ul><ul><li>clinical diagnosis </li></ul><ul><ul><li>2 major criteria or </li></ul></ul><ul><ul><li>1 major criterion plus 3 minor criteria or </li></ul></ul><ul><ul><li>5 minor criteria </li></ul></ul>
    33. 33. Diagnosis- Duke Criteria (cont.3) <ul><li>“ Probable”: </li></ul><ul><ul><li>Findings consistent with endocarditis but fall short of definite and </li></ul></ul><ul><ul><li>not rejected </li></ul></ul><ul><li>“ Rejected” </li></ul><ul><ul><li>Firm alternate diagnosis for manifestations or </li></ul></ul><ul><ul><li>resolution of manifestations ≤ 4 days of using antibiotics or </li></ul></ul><ul><ul><li>No pathologic evidence of IE at surgery or autopsy after 4 days therapy </li></ul></ul>
    34. 34. “ Echo should be done in all cases of suspected endocarditis.” (This is not all patients with fever or positive blood cultures). Circulation 1997; 95: 1686-1784
    35. 35. Differential Diagnosis <ul><li>AIE: </li></ul><ul><li>Septicemia (S. pneumonia , Staph. Aureus, G (-) bacilli, etc.) </li></ul><ul><li>SIE: </li></ul><ul><li>Rheumatic fever, Tb, SLE, myxoma, Lymphoma, glomerulonephritis, etc. </li></ul>
    36. 36. Treatment <ul><li>Goal of Therapy </li></ul><ul><li>Eradicate infection </li></ul><ul><li>Definitively treat sequelae of destructive intra-cardiac and extra-cardiac lesions </li></ul>
    37. 37. Antibiotic Therapy <ul><li>Treatment tailored to etiologic agent </li></ul><ul><li>Important to note MIC/MBC relationship for each causative organism and the antibiotic used </li></ul><ul><ul><li>High serum concentration necessary to penetrate a vascular vegetation </li></ul></ul><ul><li>Combination therapy (synergic effect, eg. PG + aminoglycosides ) </li></ul>
    38. 38. Antibiotic Therapy(2) <ul><li>Treatment before blood cultures turn positive </li></ul><ul><ul><ul><li>Suspected ABE </li></ul></ul></ul><ul><ul><ul><li>Hemodynamic instability </li></ul></ul></ul><ul><ul><li>Neither appropriate nor necessary in patient with suspected SBE who is hemodynamically stable </li></ul></ul>
    39. 39. Antibiotic Therapy(3) <ul><li>Effective antimicrobial treatment should lead to defervescence within 7 – 10 days </li></ul><ul><li>Persistent fever in: </li></ul><ul><ul><ul><li>IE due to staph, pseudomonas, culture negative </li></ul></ul></ul><ul><ul><ul><li>IE with microvascular complications/major emboli </li></ul></ul></ul><ul><ul><ul><li>Intracardiac/extracardiac septic complications </li></ul></ul></ul><ul><ul><ul><li>Drug reaction </li></ul></ul></ul><ul><li>Adequate therapy (4-6 w) </li></ul>
    40. 40. Surgical Treatment of Intra-Cardiac Complications <ul><li>NYHA Class III/IV CHF due to valve dysfunction </li></ul><ul><ul><li>Surgical mortality – 20-40% </li></ul></ul><ul><ul><li>Medical mortality – 50-90% </li></ul></ul><ul><li>Unstable prosthetic valve </li></ul><ul><ul><li>Surgical mortality – 15-55% </li></ul></ul><ul><ul><li>Medical mortality – near 100% at 6 months </li></ul></ul><ul><li>Uncontrolled infection </li></ul>
    41. 41. Surgical Treatment of Intra-Cardiac Complications(2) <ul><li>Unavailable effective antimicrobial therapy </li></ul><ul><ul><li>Fungal endocarditis </li></ul></ul><ul><ul><li>Brucella </li></ul></ul><ul><li>S. aureus PVE with any intra-cardiac complication </li></ul><ul><li>Relapse of PVE after optimal therapy </li></ul>
    42. 42. Surgical Treatment of Intra-Cardiac Complications(3) <ul><li>Relative indications </li></ul><ul><ul><li>Perivalvular extension of infection </li></ul></ul><ul><ul><li>Poorly responsive S. aureus NVE </li></ul></ul><ul><ul><li>Relapse of NVE </li></ul></ul><ul><ul><li>Culture negative NVE/PVE with persistent fever (> 10 days) </li></ul></ul><ul><ul><li>Large (> 10mm) or hypermobile vegetation </li></ul></ul><ul><ul><li>Endocarditis due to highly resistant enterococcus </li></ul></ul>
    43. 43. Prevention <ul><li>Prophylactic regimen targeted against likely organism </li></ul><ul><ul><li>Strep. viridans – oral, respiratory, eosphogeal </li></ul></ul><ul><ul><li>Enterococcus – genitourinary, gastrointestinal </li></ul></ul><ul><ul><li>S. aureus – infected skin, mucosal surfaces </li></ul></ul>
    44. 44. Prevention – the procedure <ul><li>Dental procedures known to produce bleeding </li></ul><ul><li>Tonsillectomy </li></ul><ul><li>Surgery involving GI, respiratory mucosa </li></ul><ul><li>Esophageal dilation </li></ul><ul><li>ERCP for obstruction </li></ul><ul><li>Gallbladder surgery </li></ul><ul><li>Cystoscopy, urethral dilation </li></ul><ul><li>Urethral catheter if infection present </li></ul><ul><li>Urinary tract surgery, including prostate </li></ul><ul><li>Incision & drainage of infected tissue </li></ul>
    45. 45. Prevention – the underlying lesion <ul><li>High risk lesions </li></ul><ul><ul><li>Prosthetic valves </li></ul></ul><ul><ul><li>Prior IE </li></ul></ul><ul><ul><li>Cyanotic congenital heart disease </li></ul></ul><ul><ul><li>PDA </li></ul></ul><ul><ul><li>AR, AS, MR,MS with MR </li></ul></ul><ul><ul><li>VSD </li></ul></ul><ul><ul><li>Coarctation </li></ul></ul><ul><ul><li>Surgical systemic-pulmonary shunts </li></ul></ul><ul><li>Intermediate risk </li></ul><ul><ul><li>MVP with murmur </li></ul></ul><ul><ul><li>Pure MS </li></ul></ul><ul><ul><li>Tricuspid disease </li></ul></ul><ul><ul><li>Pulmonary stenosis </li></ul></ul><ul><ul><li>ASH </li></ul></ul><ul><ul><li>Bicuspid Ao valve with no hemodynamic significance </li></ul></ul>Lesions at highest risk
    46. 46. Prevention – the underlying lesion(2) <ul><li>Low/no risk (Prophylaxis Not Recommended) </li></ul><ul><ul><li>MVP without murmur </li></ul></ul><ul><ul><li>Trivial valvular regurg. </li></ul></ul><ul><ul><li>Isolated ASD </li></ul></ul><ul><ul><li>Implanted device (pacer, ICD) </li></ul></ul><ul><ul><li>CAD </li></ul></ul><ul><ul><li>CABG </li></ul></ul>
    47. 47. Chemoprophylaxis <ul><li>Adult Prophylaxis: Dental, Oral, Respiratory, Esophageal </li></ul><ul><li>Standard Regimen </li></ul><ul><ul><li>Amoxicillin 2g PO 1h before procedure or </li></ul></ul><ul><ul><li>Ampicillin 2g IM/IV 30m before procedure </li></ul></ul><ul><li>Penicillin Allergic </li></ul><ul><ul><li>Clindamycin </li></ul></ul><ul><ul><ul><li>600 mg PO 1h before procedure or </li></ul></ul></ul><ul><ul><ul><li>600 mg IV 30m before </li></ul></ul></ul><ul><ul><li>Cephalexin OR Cefadroxil 2g PO 1 hour before </li></ul></ul><ul><ul><li>Cefazolin 1.0g IM/IV 30 min before procedure </li></ul></ul><ul><ul><li>Azithromycin or Clarithromycin 500mg PO 1h before </li></ul></ul>
    48. 48. <ul><li>Adult Genitourinary or Gastrointestinal Procedures </li></ul><ul><li>High Risk Patients </li></ul><ul><li>Standard Regimen </li></ul><ul><ul><ul><ul><li>Before procedure (30 minutes): </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Ampicillin 2g IV/IM AND </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Gentamicin 1.5 mg/kg (MAX 120 mg) IM/IV </li></ul></ul></ul></ul></ul><ul><ul><ul><li>After procedure (6 hours later) </li></ul></ul></ul><ul><ul><ul><ul><li>Ampicillin 1g IM/IV OR </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Amoxicillin 1g PO </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Penicillin Allergic </li></ul></ul></ul></ul><ul><ul><ul><li>Complete infusion 30 minutes before procedure </li></ul></ul></ul><ul><ul><ul><ul><li>Vancomycin 1g IV over 1-2h AND </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Gentamicin 1.5 mg/kg IV/IM (MAX 120 mg) </li></ul></ul></ul></ul><ul><li>Moderate Risk Patients </li></ul><ul><li>Standard Regimen </li></ul><ul><ul><ul><li>Amoxicillin 2g PO 1h before OR </li></ul></ul></ul><ul><ul><ul><li>Ampicillin 2g IM/IV 30m before </li></ul></ul></ul><ul><ul><ul><li>Penicillin Allergic </li></ul></ul></ul><ul><ul><ul><li>Vancomycin 1g IV over 1-2h, complete 30m before </li></ul></ul></ul>
    49. 49. Bring Home Message <ul><li>How is the pathogenesis of IE? </li></ul><ul><li>What’s the composition of a vegetation? </li></ul><ul><li>What are the characteristics of HACEK? </li></ul><ul><li>How is the chemotherapeutic rule for IE? </li></ul><ul><li>How is the indication of surgical treatment for IE? </li></ul><ul><li>What are predisposing factors? How is the rule of chemoprophylaxis for IE? </li></ul>
    50. 50. Thank you!
    51. 51. Predisposing Conditions Strom BL, Abrutyn E, Berlin JA, Kinman JL, Feldman RS, Stolley PD, et al. Ann Intern Med. 1998;129:761-9. IV drug users and nosocomial cases excluded.
    52. 52. Nonbacterial Thrombotic Endocarditis <ul><li>Sterile platelet-fibrin deposits </li></ul><ul><li>Occur at sites of eddy currents or jet streams created by pre-existing cardiac disease </li></ul><ul><li>Create the “soil” for bacterial deposition. </li></ul><ul><li>Characteristically, non-inflammatory </li></ul>
    53. 53. Infection Growth of vegetation by platelet-fibrin deposition yields a sanctuary for bacteria.
    54. 54. Streptococci in IE
    55. 55. Viridans Streptococci <ul><li>30-65% of native valve endocarditis </li></ul><ul><li>Normal oral commensals </li></ul><ul><li>A group, composed of several species: </li></ul><ul><ul><li>S. mitior, S. sanguis, S. mutans,etc. </li></ul></ul><ul><ul><li>Alpha-hemolytic, non-typable </li></ul></ul><ul><li>Typical agents of classic “SBE” </li></ul>
    56. 56. Other Streptococci <ul><li>S. bovis </li></ul><ul><ul><li>Lancefield group D </li></ul></ul><ul><ul><li>Gut flora: associated with GI pathology </li></ul></ul><ul><li>S. pneumonia </li></ul><ul><ul><li>1-3% of cases of IE with predilection for AV </li></ul></ul><ul><ul><li>Usually, in those with immune suppression </li></ul></ul><ul><ul><ul><li>DM and Ethanolism </li></ul></ul></ul><ul><li>Group B Streptococci </li></ul><ul><ul><li>Elderly with chronic disease </li></ul></ul>
    57. 57. Enterococcus <ul><li>Normal inhabitant of GI tract. </li></ul><ul><li>Frequently encountered in UTIs. </li></ul><ul><li>Up to 40% of cases without identified underlying predisposition to IE. </li></ul><ul><li>Difficult to treat due to drug resistance. </li></ul>
    58. 58. Staphylococci <ul><li>Coagulase Positive (Staph. aureus) </li></ul><ul><ul><li>a major causative agent in all populations of IE </li></ul></ul><ul><ul><li>typically produces “acute” IE </li></ul></ul><ul><ul><ul><li>fulminant, rapidly progressive with few immunologic signs. </li></ul></ul></ul><ul><ul><ul><li>CNS complications in 30-50% </li></ul></ul></ul><ul><li>Coagulase Negative (Staph. epi, et al) </li></ul><ul><ul><li>Major cause of PVE. 3-8% of NVE. </li></ul></ul>
    59. 59. Fungi <ul><li>Commonly encountered agents: </li></ul><ul><ul><li>Candida, Torulopsis, Aspergillus </li></ul></ul><ul><li>Predispositions </li></ul><ul><ul><li>Prosthetic valves </li></ul></ul><ul><ul><li>IVDA </li></ul></ul><ul><ul><li>Immunosupression </li></ul></ul><ul><ul><li>Hyperalimentation </li></ul></ul><ul><ul><li>Prolonged abx treatment </li></ul></ul><ul><li>Large vegetations and frequent embolic events. </li></ul>
    60. 60. Other Organisms <ul><li>Pseudomonas </li></ul><ul><li>Brucella </li></ul><ul><li>Diphtheroids </li></ul><ul><li>Listeria </li></ul><ul><li>Bartonella </li></ul><ul><li>Coxsiella </li></ul><ul><li>Chlamydia </li></ul>
    61. 61. Diagnosis <ul><li>Frequently difficult to diagnose with certainty. </li></ul><ul><ul><li>Highly variable and often non-specific presentation. </li></ul></ul><ul><li>Overdiagnosis and Underdiagnosis are common. </li></ul>
    62. 62. Diagnosis <ul><li>Classic Clinical Approach: </li></ul><ul><ul><li>Von Reyn (Beth Israel) Criteria </li></ul></ul><ul><ul><ul><li>Limitations: </li></ul></ul></ul><ul><ul><ul><ul><li>No Use of Echo. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>IVDA not identified as a predisposition </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Lacks sensitivity for “acute” cases. </li></ul></ul></ul></ul><ul><li>Incorporation of Echo: </li></ul><ul><ul><li>Durack (Duke) Criteria </li></ul></ul><ul><ul><ul><li>Increases proportion of definite diagnoses. </li></ul></ul></ul>
    63. 63. Use of Echo in Diagnosis of IE <ul><li>Native Valves-ACC Guidelines: </li></ul><ul><ul><li>Detection/characterization of valvular lesions </li></ul></ul><ul><ul><li>Detection of vegetations and characterization of lesions in patients with CHD </li></ul></ul><ul><ul><li>Detection of associated abnormalities </li></ul></ul><ul><ul><li>Reevaluation studies in complex IE </li></ul></ul><ul><ul><li>Evaluation of patients with high suspicion of culture-negative IE </li></ul></ul>
    64. 64. Use of Echo in Diagnosis of IE <ul><li>Prosthetic Valves-ACC Guidelines: </li></ul><ul><ul><li>Detection/characterization of valvular lesions </li></ul></ul><ul><ul><li>Detection of associated abnormalities </li></ul></ul><ul><ul><li>Reevaluation in complex IE </li></ul></ul><ul><ul><li>Evaluation of suspected IE and negative cultures </li></ul></ul><ul><ul><li>Evaluation of persistent fever without known source </li></ul></ul>
    65. 65. Use of Echo in Diagnosis of IE <ul><li>TEE: </li></ul><ul><ul><li>Prosthetic valves </li></ul></ul><ul><ul><li>Poor visualization on TTE and high suspicion </li></ul></ul><ul><ul><li>Detection of associated complications </li></ul></ul><ul><ul><li>Preoperative </li></ul></ul><ul><ul><li>Reevaluation in complex IE </li></ul></ul>
    66. 66. Medical Management <ul><li>Tailor therapy to results of susceptibility testing. </li></ul><ul><li>Use parenteral drugs. </li></ul><ul><li>Plan for prolonged courses of abx. </li></ul><ul><ul><li>Be vigilant for adverse drug effects. </li></ul></ul><ul><li>Use bacteri cidal agents. </li></ul><ul><li>Synergistic combinations are useful. </li></ul><ul><li>Monitor levels of aminoglycosides. </li></ul>
    67. 67. Culture Negative Endocarditis <ul><li>Most common cause is recent use of abx. </li></ul><ul><li>Fastidious organisms </li></ul><ul><li>Fungal </li></ul><ul><li>Intracellular agents: Bartonella, chlamdia, viruses. </li></ul><ul><li>Non-infectious (marantic) </li></ul>
    68. 68. Anticoagulation “ If anticoagulation is indicated for another reason it should be continued. Anticoagulation does not prevent embolization due to IE.” ACC guidelines on Diagnosis and Management of Infective Endocarditis.
    69. 69. Class I Indications for Surgery <ul><li>Acute AR or MR with heart failure. </li></ul><ul><li>Acute AR with tachycardia and early closure of the MV. </li></ul><ul><li>Fungal endocarditis. </li></ul><ul><li>Annular or aortic abscess. </li></ul><ul><li>Sinus or aortic aneurysm. </li></ul><ul><li>Persistent bacteremia and valve dysfunction </li></ul><ul><ul><li>After 7-10 days of appropriate antibiotics. </li></ul></ul>Circulation. 98(18):1949-1984, 1998
    70. 70. Other Indications for Surgery <ul><li>Class IIa </li></ul><ul><ul><li>Recurrent emboli after appropriate abx. </li></ul></ul><ul><ul><li>Agent with known poor response to abx (GNR) with valve dysfunction. </li></ul></ul><ul><li>Class IIb </li></ul><ul><ul><li>Mobile vegetations >10 mm. </li></ul></ul><ul><li>Class III </li></ul><ul><ul><li>Early infections of MV that can likely be repaired. </li></ul></ul><ul><ul><li>Persistent pyrexia and leucocytosis with negative blood cultures. </li></ul></ul>Circulation. 98(18):1949-1984, 1998
    71. 71. Bayer AS, et al. Circ 98:25, 2936-48. 22/29 Dec 98
    72. 72. Features of High Risk for Complications <ul><li>Prosthetic cardiac valves </li></ul><ul><li>Left-sided IE </li></ul><ul><li>Staphylococcus aureus </li></ul><ul><li>Fungal IE </li></ul><ul><li>Prior IE </li></ul>
    73. 73. Features of High Risk for Complications <ul><li>Prolonged symptoms (>9 months) </li></ul><ul><li>Cyanotic CHD </li></ul><ul><li>Pulmonary-to-systemic shunts </li></ul><ul><li>Poor response to antimicrobial therapy </li></ul>
    74. 74. Complications Occur in Over Half of All Cases <ul><li>Embolic: CNS and Peripheral </li></ul><ul><ul><li>Ischemic </li></ul></ul><ul><ul><li>Hemorrhagic </li></ul></ul><ul><ul><li>Septic: </li></ul></ul><ul><ul><ul><li>mycotic aneurysm </li></ul></ul></ul><ul><ul><ul><li>metastatic abscess </li></ul></ul></ul><ul><li>Local invasive </li></ul><ul><ul><li>Conduction abnormalities </li></ul></ul><ul><ul><li>Valvular dysfunction </li></ul></ul><ul><ul><li>CHF </li></ul></ul><ul><li>Glomerulonephritis </li></ul>
    75. 75. CHF <ul><li>High associated mortality </li></ul><ul><ul><li>Accounts for 80-90% of IE deaths </li></ul></ul><ul><li>Leading indication for surgery </li></ul><ul><li>More common with AV involvement </li></ul><ul><li>More common with Staph aureus ? </li></ul><ul><li>Surgery is strongly indicated in most cases. </li></ul><ul><ul><li>In-house death reduced from 51% to 9%. </li></ul></ul><ul><ul><li>Once CHF develops, surgery should be performed promptly. </li></ul></ul>
    76. 76. Embolic Events <ul><li>Occurs in 22-50% of cases. </li></ul><ul><li>65% of events occur in CNS </li></ul><ul><ul><li>90% of these in MCA distribution </li></ul></ul><ul><ul><li>Associated with high mortality </li></ul></ul><ul><li>Highest incidence with S. aureus , Candida sp ., and HACEK organisms. </li></ul>
    77. 77. Embolic Events <ul><li>Risk for embolism drops dramatically within two weeks of antibiotic therapy institution. </li></ul><ul><ul><li>13 to <1.2 events/1000 patient-days </li></ul></ul><ul><ul><li>MV disease > AV disease, AML disease the highest. </li></ul></ul><ul><li>Size of vegetation and embolic potential remain incompletely explained. </li></ul>
    78. 78. Embolic Events: an Aggressive Approach Clinical Embolic Event (CNS or peripheral) CT/MR of Brain Small, ischemic infarcts & Mild neurologic impairment Vegetations present by echo Prompt Surgery Large or hemorrhagic infarct Observe Blaustein AS Card Clin 14:3,1996
    79. 79. Mycotic Aneurysm <ul><li>2-5% of all cerebral aneurysms </li></ul><ul><li>More common in debilitated patients </li></ul><ul><li>Suspect when encountered in… </li></ul><ul><ul><li>Persistent fever </li></ul></ul><ul><ul><li>Pulsatile mass/erythema in peripheral regions </li></ul></ul><ul><ul><li>Headache, meningitis, neuro deficit for cerebral </li></ul></ul><ul><li>Surgery recommended whenever possible. </li></ul>
    80. 80. Periannular Extension of Infection <ul><li>10-40% of all NVE </li></ul><ul><ul><li>AV>TV </li></ul></ul><ul><li>56-100% of all PVE </li></ul><ul><ul><li>annulus is usually the primary site of infection </li></ul></ul><ul><li>May develop into fistulous tracts or shunts. </li></ul><ul><li>New AV block has a PPV of 88%. </li></ul><ul><li>Best diagnosed by TEE. </li></ul><ul><li>Best surgical option is frequently the homograft. </li></ul><ul><ul><li>Improved penetration of antibiotics . </li></ul></ul>
    81. 81. Circulation. 96(1):358-366, 1997 July 1. Prophylaxis
    82. 82. High Risk: Prophylaxis Recommended <ul><li>Prosthetic cardiac valves, including bioprosthetic and homograft valves </li></ul><ul><li>Previous bacterial endocarditis </li></ul><ul><li>Complex cyanotic congenital heart disease (eg, single ventricle states, transposition of the great arteries, tetralogy of Fallot) </li></ul><ul><li>Surgically constructed systemic pulmonary shunts or conduits </li></ul>
    83. 83. Moderate Risk: Prophylaxis Recommended <ul><li>Most other congenital cardiac malformations (other than above and below) </li></ul><ul><li>Acquired valvular dysfunction (eg, rheumatic heart disease) </li></ul><ul><li>Hypertrophic cardiomyopathy </li></ul><ul><li>Mitral valve prolapse with valvular regurgitation and/or thickened leaflets </li></ul>
    84. 84. Low Risk: Prophylaxis Not Recommended <ul><li>Isolated secundum atrial septal defect </li></ul><ul><li>Surgical repair of atrial septal defect, ventricular septal defect, or patent ductus arteriosus </li></ul><ul><ul><li>(without residua beyond 6 mo) </li></ul></ul><ul><li>Previous coronary artery bypass graft surgery </li></ul><ul><li>Mitral valve prolapse without valvular regurgitation * </li></ul>
    85. 85. Low Risk: Prophylaxis Not Recommended <ul><li>Physiologic, functional, or innocent heart murmurs </li></ul><ul><li>Previous Kawasaki disease without valvular dysfunction </li></ul><ul><li>Previous rheumatic fever without valvular dysfunction </li></ul><ul><li>Cardiac pacemakers (intravascular and epicardial) and implanted defibrillators </li></ul>
    86. 86. Prophylaxis Recommended <ul><li>Respiratory Tract </li></ul><ul><ul><li>Tonsillectomy </li></ul></ul><ul><ul><li>Violation of respiratory mucosa. </li></ul></ul><ul><ul><li>Rigid bronchoscopy. </li></ul></ul><ul><li>Gastrointestinal Tract </li></ul><ul><ul><li>Esophageal sclerotherapy or stricture dilation </li></ul></ul><ul><ul><li>ERCP </li></ul></ul><ul><ul><li>Billiary surgery </li></ul></ul><ul><ul><li>Violation of intestinal mucosa </li></ul></ul><ul><li>GU Tract </li></ul><ul><ul><li>Prostate surgery </li></ul></ul><ul><ul><li>Cystoscopy </li></ul></ul><ul><ul><li>Urethral dilatation </li></ul></ul>
    87. 87. Prophylaxis Not Recommended <ul><li>Respiratory Tract </li></ul><ul><ul><li>e ndotracheal intubation </li></ul></ul><ul><ul><li>Flexible bronchoscopy </li></ul></ul><ul><ul><li>PE tubes </li></ul></ul><ul><li>GI Tract </li></ul><ul><ul><li>TEE </li></ul></ul><ul><ul><li>EGD </li></ul></ul>
    88. 88. Prophylaxis Not Recommended <ul><li>GU Tract </li></ul><ul><ul><li>Vaginal hysterectomy </li></ul></ul><ul><ul><li>Vaginal delivery </li></ul></ul><ul><ul><li>C - section </li></ul></ul><ul><ul><li>In uninfected tissue: </li></ul></ul><ul><ul><ul><li>D and C/Ab </li></ul></ul></ul><ul><ul><ul><li>Urethral cath </li></ul></ul></ul><ul><ul><ul><li>Sterilization </li></ul></ul></ul><ul><ul><ul><li>IUDs </li></ul></ul></ul><ul><ul><li>Circumcision </li></ul></ul>
    89. 89. Antibiotic Prophylaxis
    90. 90. Antibiotic Prophylaxis
    91. 91. Infective Endocarditis Questions?
    92. 92. “ The practice of medicine is an art, not a trade; a calling, not a business; a calling in which your heart will be exercised equally with your head. Often the best part of your work will have nothing to do with potions and powders, but with the exercise of an influence of the strong upon the weak, of the righteous upon the wicked, of the wise upon the foolish.” William Osler
    93. 97. Use of Echo in Diagnosis of IE Bayer AS, et al. Circ 98:25, 2936-48. 22/29 Dec 98
    94. 99. Management of IE
    95. 100. The Sanford Guide to Antimicrobial Therapy Gilbert DN, Moellering RC, Sande MA, eds. 28th ed. 1998. Antimicrobial Therapy for IE
    96. 101. Sanford, et al.
    97. 102. Sanford, et al.
    98. 103. Sanford, et al. + gent x 14 d
    99. 104. Surgery for PVE
    100. 105. IE Prophylaxis in MVP
    101. 106. Antibiotic Prophylaxis
    102. 107. Antibiotic Prophylaxis
    103. 108. IE: More than a nostalgic disease. <ul><li>“ One of the most serious of all infections.”* </li></ul><ul><ul><li>Is uniformly fatal if untreated. </li></ul></ul><ul><ul><li>Continues to have a high case fatality rate even in antibiotic era. </li></ul></ul><ul><ul><ul><li>4th leading cause of life-threatening ID. </li></ul></ul></ul><ul><li>Incidence is increasing. </li></ul>* Pathologic Basis of Disease. Cotran, Kumar, Robbins. 4th Ed.
    104. 109. IV Drug Users <ul><li>Accounts for 25% of cases of IE in US. </li></ul><ul><li>5:1 male:female </li></ul><ul><li>Pre-existing valvular diseases uncommon. </li></ul><ul><li>Variable microbiology. </li></ul><ul><li>Mortality<10%. </li></ul>
    105. 110. Prosthetic Valve IE <ul><li>Affects 3% of prosthesis patients. </li></ul><ul><ul><li>Highest risk in first 6 months post op. </li></ul></ul><ul><li>Accounts for 10-20% of all IE cases. </li></ul><ul><li>Increased risk in… </li></ul><ul><ul><li>Males </li></ul></ul><ul><ul><li>Blacks </li></ul></ul><ul><ul><li>Prolonged pump time </li></ul></ul><ul><ul><li>Multiple valve replacement </li></ul></ul>
    106. 111. Prosthetic Valve IE <ul><li>“ Early” (<2 months)-Staph epi </li></ul><ul><li>“ late” (after 2 months)- mimics NVE </li></ul>