CASE PRESENTATION

1. CASE PRESENTATION DR. T. BURNS ZAK BAYAT PGY-2

2. CASE OF MR. M.C. 45 year old Recent onset of diabetes

3. Early May, �05: Fever, malaise, left thigh infection Had I&D left leg abscess Hypotensive --- ICU admission Dx: Urosepsis (grew E. Coli) Rx: IV fluids and antibiotics Improved; home on May 13th on Ceftin PO

4. May 25, 2005: Malaise at home and fever Acute onset red-purple purpuric leg rash ER -- Admitted SDU with Dx of sepsis or ? DIC O/E: - morbid obesity - chest clear - heart sounds normal, no murmurs - abdomen clear

5. �continued O/E: swollen legs with large purple-blue purpuric lesions with ? suggestion of bullae formation LABS: Hb 105 WBC 21 Plt 105 INR 1.31 CXR: Cavitating lung lesion Blood cultures: Group B Strep.

6. �continued Rx: IV penicillin --- better Leg lesions improving; surgical consult CT Chest: Cavitating lesion ? Wegner�s Granulomatosis ANCA: pending Discharged June 4 on Insulin and Pen V

7. June 16, 2005: Readmitted with SOB, no sweats or fevers reported O/E: - leg lesion as previous - heart sounds normal, no murmurs - resp: crackles, no wheeze CXR: right pleural effusion Thoracentesis: exudative; culture and cytology both negative

8. �continued: p-ANCA and c-ANCA both negative Blood cultures: negative T.T. Echo: severe tricuspid regurgitation with vegetation T.E.E @ LHSC: confirmed abscess Rx: IV gentamicin and IV penicillin Discharged home July 15 with PICC line

9. July 21, 2005: Continued SOB CXR: Hydro/Pneumothorax Thoracotomy and decortication for empyema Continued on gentamicin and penicilllin Cultures on thoracotomy specimen negative Discharged home August 4th.

10. August 19th, 2005: In Office: c/o dizziness Peak gentamicin mild elevation; trough normal Antibiotic therapy d/c after 7 weeks Referral to Dr. Pfleugfelder regarding tricuspid valve replacement

11. September 5th, 2005: c/o of swelling right chest and neck CT: small right hydropneumothorax pneumomediastinum Dx: S/C emphysema Rx: S/C chest tube inserted -- Heimlich valve

12. INFECTIVE ENDOCARDITIS

13. Infective Endocarditis Essential characteristics General definitions and epidemiology NVE I.V. drug abuse PVE Pathogenesis Pathophysiology Clinical features Treatment

14. Infective Endocarditis Febrile illness Persistent bacteremia Characteristic lesion of microbial infection of the endothelial surface of the heart Variable in size Amorphous mass of fibrin & platelets Abundant organisms Few inflammatory cells

16. Infective Endocarditis Typically involves the valves May involve all structures of the heart Chordae tendinae Sites of shunting Mural lesions Infection of vascular shunts, by strict definition, is endarteritis, but lesion is the same Majority of cases caused by streptococcus, staphylococcus, enterococcus, or fastidious gram negative cocco-bacillary forms

17. Infective Endocarditis Gram negative organisms P. aeruginosa most common HACEK - slow growing, fastidious organisms that may need 3 weeks to grow out of culture Haemophilus sp. Actinobacillus Cardiobacterium Eikenella Kingella

18. Table 1. Microbiologic Features of Native-Valve and Prosthetic-Valve Endocarditis.Table 1. Microbiologic Features of Native-Valve and Prosthetic-Valve Endocarditis.

19. Infective Endocarditis Acute Toxic presentation Progressive valve destruction & metastatic infection developing in days to weeks Most commonly caused by S. aureus Subacute Mild toxicity Presentation over weeks to months Rarely leads to metastatic infection Most commonly Strep. viridans or enterococcus

20. Infective Endocarditis Case rate may vary between 2-3 cases /100,000 to as high as 15-30/100,000 depending on incidence of i.v. drug abuse and age of the population 55-75% of patients with native valve endocarditis (NVE) have underlying valve abnormalities MVP Rheumatic Congenital AI or: i.v. drug abuse

21. Infective Endocarditis Case rates 7-25% of cases involve prosthetic valves 25-45% of cases predisposing condition can not be identified

22. Infective Endocarditis RISK FACTORS MVP � prominent predisposing factor High prevalence in population 2-4% 20% in young women Accounts for 7 � 30% NVE in cases not related to drug abuse or nosocomial infection Relative risk in MVP ~3.5 � 8.2, largely confined to patients with murmur, but also increased in men and patients >45 years old MVP with murmur � incidence IE 52/100/000 pt. years MVP w/o murmur � incidence IE 4.6/100,000 pt. years

23. Infective Endocarditis RISK FACTORS Rheumatic Heart Disease 20 � 25% of cases of IE in 1970�s & 80�s 7 � 18% of cases in recent reported series Mitral site more common in women Aortic site more common in men Congenital Heart Disease 10 � 20% of cases in young adults 8% of cases in older adults PDA, VSD, bicuspid aortic valve (esp. in men>60)

24. Infective Endocarditis Intravenous Drug Abuse Risk is 2 � 5% per pt./year Tendency to involve right-sided valves Distribution in clinical series 46 � 78% tricuspid 24 � 32% mitral 8 � 19% aortic Underlying valve normal in 75 � 93% S. aureus predominant organism (>50%, 60-70% of tricuspid cases)

25. Infective Endocarditis Intravenous Drug Abuse Increased frequency of gram negative infection such as P. aeruginosa & fungal infections High concordance of HIV positivity & IE (27-73%) HIV status does not in itself modify clinical picture Survival is decreased if CD4 count < 200/mm3

26. Infective Endocarditis Prosthetic Valve Endocarditis (PVE) 10 � 30% of all cases in developed nations Cumulative incidence 1.4 � 3.1% at 12 months 3.2 � 5.7% at 5 years Early PVE � within 60 days Nosocomial (s. epi predominates) Late PVE � after 60 days Community (same organisms as NVE)

27. Infective Endocarditis PATHOLOGY NVE infection is largely confined to leaflets PVE infection commonly extends beyond valve ring into annulus/periannular tissue Ring abscesses Septal abscesses Fistulae Prosthetic dehiscence Invasive infection more common in aortic position and if onset is early

28. Infective Endocarditis PATHOGENESIS

29. Infective Endocarditis Nonbacterial Thrombotic Endocarditis Endothelial injury Hypercoagulable state Lesions seen at coaptation points of valves Atrial surface mitral/tricuspid Ventricular surface aortic/pulmonic Modes of endothelial injury High velocity jet Flow from high pressure to low pressure chamber Flow across narrow orifice of high velocity Bacteria deposited on edges of low pressure sink or site of jet impaction

30. Venturi Effect

31. Conversion of NBTE to IE Frequency & magnitude of bacteremia Density of colonizing bacteria Oral > GU > GI Disease state of surface Infected surface > colonized surface Extent of trauma Resistance of organism to host defenses Most aerobic gram negatives susceptible to complement-mediated bactericidal effect of serum Tendency to adhere to endothelium Dextran producing strep Fibronectin receptors on staph, enterococcus, strep, Candida

32. Pathophysiology Clinical manifestations Direct Constitutional symptoms of infection (cytokine) Indirect Local destructive effects of infection Embolization � septic or bland Hematogenous seeding of infection N.B. may present as local infection or persistent fever, metastatic abscesses may be small, miliary Immune response Immune complex or complement-mediated

33. Pathophysiology Local destructive effects Valvular distortion/destruction Chordal rupture Perforation/fistula formation Paravalvular abscess Conduction abnormalities Purulent pericarditis Functional valve obstruction

34. Pathophysiology Embolization Clinically evident 11 � 43% of patients Pathologically present 45 � 65% High risk for embolization Large > 10 mm vegetation Hypermobile vegetation Mitral vegetations (esp. anterior leaflet) Pulmonary (septic) � 65 � 75% of i.v. drug abusers with tricuspid IE Left sided versus right sided lesions

35. Clinical Features Interval between index bacteremia & onset of sx�s usually < 2 weeks May be substantially longer in early PVE Fever most common sign May be absent in elderly/debilitated pt. Murmur present in 80 � 85% Generally indication of underlying lesion Frequently absent in tricuspid IE Changing murmur

36. Classical Peripheral Manifestations Less common today Not seen in tricuspid endocarditis Petechiae most common

37. Janeway Lesions

38. Splinter Hemorrhage

39. Osler�s Nodes

40. Subconjunctival Hemorrhages

41. Roth�s Spots

42. Clinical Features Systemic emboli Incidence decreases with effective anti-microbial Rx Neurological sequelae Embolic stroke 15 � 20% of patients Mycotic aneurysm Cerebritis CHF Due to mechanical disruption High mortality without surgical intervention Renal insufficiency Immune complex mediated Impaired hemodynamics/drug toxicity

43. Diagnosis Published criteria for diagnostic purposes in obscure cases High index of suspicion in patients with predisposing anatomy or behavior Blood cultures Echocardiography TTE � 60% sensitivity TEE � 80 � 95% sensitive

44. Table 3. Modified Duke Criteria for the Diagnosis of Infective Endocarditis.Table 3. Modified Duke Criteria for the Diagnosis of Infective Endocarditis.

45. Goals of Therapy Eradicate infection Definitively treat sequelae of destructive intra-cardiac and extra-cardiac lesions

46. Antibiotic Therapy Treatment tailored to etiologic agent Important to note MIC/MBC relationship for each causative organism and the antibiotic used High serum concentration necessary to penetrate avascular vegetation

47. Table 4. Usual Antimicrobial Therapy for Common Causes of Infective Endocarditis.Table 4. Usual Antimicrobial Therapy for Common Causes of Infective Endocarditis.

48. Antibiotic Therapy Treatment before blood cultures turn positive Suspected ABE Hemodynamic instability Neither appropriate nor necessary in patient with suspected SBE who is hemodynamically stable

49. Antibiotic Therapy Effective antimicrobial treatment should lead to defervescence within 7 � 10 days Persistent fever in: IE due to staph, pseudomonas, culture negative IE with microvascular complications/major emboli Intracardiac/extracardiac septic complications Drug reaction

50. Surgical Treatment of Intra-Cardiac Complications NYHA Class III/IV CHF due to valve dysfunction Surgical mortality � 20-40% Medical mortality � 50-90% Unstable prosthetic valve Surgical mortality � 15-55% Medical mortality � near 100% at 6 months Uncontrolled infection

51. Surgical Treatment of Intra-Cardiac Complications Unavailable effective antimicrobial therapy Fungal endocarditis Brucella S. aureus PVE with any intra-cardiac complication Relapse of PVE after optimal therapy

52. Surgical Treatment of Intra-Cardiac Complications Relative indications Perivalvular extension of infection Poorly responsive S. aureus NVE Relapse of NVE Culture negative NVE/PVE with persistent fever (> 10 days) Large (> 10mm) or hypermobile vegetation Endocarditis due to highly resistant enterococcus

53. Prevention Prophylactic regimen targeted against likely organism Strep. viridans � oral, respiratory, eosphogeal Enterococcus � genitourinary, gastrointestinal S. aureus � infected skin, mucosal surfaces

54. Prevention � the procedure Dental procedures known to produce bleeding Tonsillectomy Surgery involving GI, respiratory mucosa Esophageal dilation ERCP for obstruction Gallbladder surgery Cystoscopy, urethral dilation Urethral catheter if infection present Urinary tract surgery, including prostate I&D of infected tissue

55. Prevention � the underlying lesion High risk lesions Prosthetic valves Prior IE Cyanotic congenital heart disease PDA AR, AS, MR,MS with MR VSD Coarctation Surgical systemic-pulmonary shunts Intermediate risk MVP with murmur Pure MS Tricuspid disease Pulmonary stenosis ASH Bicuspid Ao valve with no hemodynamic significance

56. Prevention � the underlying lesion Low/no risk MVP without murmur Trivial valvular regurg. Isolated ASD Implanted device (pacer, ICD) CAD CABG

57. Chemoprophylaxis

58. SUMMARY Infective endocarditis is a serious systemic infection Most textbook descriptions of clinical features relate to left sided endocarditis, which are most common BEWARE of right sided endocarditis