INFECTIVE ENDOCARDITIS

1. INFECTIVE ENDOCARDITIS   Dipin.S Junior Resident Internal medicine

2. Definition Infective endocarditis (IE) is a microbial infection of the endothelial surface of the heart or iatrogenic foreign bodies like prosthetic valves or other intracardiac devices Infective Endarteritis – AV shunts, Arterioarterial shunts, Coarctation of aorta

3.  The prototypic lesion The vegetation Variable in size Amorphous mass of fibrin & platelets Abundant organisms Few inflammatory cells

4. Pathogenesis

5. 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

6. Conversion of NBTE to BE Transient bacteremia Traumatization of mucosal surface colonized with bacteria (oral, GI) Low grade, cleared in 15-30 minutes Susceptibility to complement-mediated bacterial killing Leads to concept of prophylaxis

7. 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 Bracht Wachter bodies Bracht-Wachter bodies are a finding in infective endocarditis[1] consisting of yellow-white miliary spots in the myocardium. Histologically, these are collections of chronic inflammatory cells, mainly lymphocytes[2] and histiocytes Bracht-Wachter bodies are a finding in infective endocarditis[1] consisting of yellow-white miliary spots in the myocardium. Histologically, these are collections of chronic inflammatory cells, mainly lymphocytes[2] and histiocytes

8. Epidemiology 1.7 to 6.2 cases per 100,000 population per year in US The cumulative rate of prosthetic valve endocarditis is 1.5 to 3.0% at 1 year after valve replacement. 3 to 6% at 5 years; the risk is greatest during the first 6 months after valve replacement. Men predominate in most case series, with male-to-female ratios ranging from 2:1 to 9:1

9. Risk Factors Structural heart disease Rheumatic, congenital, aging Prosthetic heart valves Injected drug use Invasive procedures (Intracardiac pacemaker, ICD , AV Fistula) Indwelling vascular devices Other infection with bacteremia (e.g. pneumonia, meningitis) Immunocompromised states History of infective endocarditis

10. Viridans Streptococci 30-65% of native valve endocarditis Normal oral commensals A group, composed of several species: S. mitior, S. sanguis, S. mutans,etc. Alpha-hemolytic, non-typable Typical agents of classic “SBE”

11. Other Streptococci S. bovis Lancefield group D Gut flora: associated with GI pathology S. pneumonia 1-3% of cases of IE with predilection for AV Usually, in those with immune suppression DM and Alcoholism Group B Streptococci Elderly with chronic disease

12. Enterococcus Normal inhabitant of GI tract. Frequently encountered in UTIs. Up to 40% of cases without identified underlying predisposition to IE. Difficult to treat due to drug resistance.

13. Staphylococci Coagulase Positive (Staph. aureus) a major causative agent in all populations of IE typically produces “acute” IE fulminant, rapidly progressive with few immunologic signs. CNS complications in 30-50% Coagulase Negative (Staph. Epi) Major cause of PVE. 3-8% of NVE.

14. HACEK organisms Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella Gram negative inhabitants of the upper airways. Large vegetations, high likelihood of embolization. Slow growing: hold cultures for 3 weeks. Traditionally sensitive to beta lactams, now some produce beta lactamase.

15. Fungi Commonly encountered agents: Candida, Torulopsis, Aspergillus Predispositions Prosthetic valves IVDA Immunosupression Hyperalimentation Prolonged antibiotic treatment Large vegetations and frequent embolic events.

16. Other Organisms Pseudomonas Diphtheroids Listeria Bartonella Coxiella,Legionella,salmonella,brucella Chlamydia,Abiotropia Bartonella ,tropheryma, streptobacillus

17. BCNE Blood culture sterile in 31 % (western data) Sterile culture in India – 48 to 54 % Blood culture is positive only on 67.7% of the cases in recently published data from India Causes Antibiotic therapy before blood culture Fastidius or atypical organisms do not grow in routine culture media Fungal or viral Endocarditis

18. IV Drug Users Accounts for 25% of cases of IE in US. 5:1 male:female Pre-existing valvular diseases uncommon. Variable microbiology. Mortality<10%.

19. Prosthetic Valve IE Affects 3% of prosthesis patients. Highest risk in first 6 months post op. Accounts for 10-20% of all IE cases. Increased risk in… Males Blacks Multiple valve replacement

20. Prosthetic Valve IE “Early” (<2 months)-Staph epi “Late” (after 2 months)- mimics NVE

21. Clinical features High index of clinical suspicion is the cornerstone of early diagnosis Symptoms Fever, sweats, chills Anorexia, malaise, weight loss Signs Anemia (normochromic, normocytic) Splenomegaly Microscopic hematuria, proteinuria New or changing heart murmur, CHF Embolic or immunologic dermatologic signs Hypergammaglobulinemia, elevated ESR, CRP, RF

22. CLINICAL MANIFESTATIONS

23. Fever is the most common symptom and sign in patients with IE. Fever may be absent or minimal in elderly in those with CHF, severe debility, chronic renal failure NVE caused by coagulase-negative staphylococci

24. Cardiac murmur New changing regurgitant murmur is the hallmark of IE Murmurs are commonly not audible in Tricuspid valve IE Acute NVE due to S. aureus. Murmurs are heard in only 30 to 45 percent of patients on initial evaluation but are ultimately noted in 75 to 85 percent.

25. Embolic phenomina include systemic,cerebral and pumonary emboli are common in >50 % cases.

27. Cardiac Pathologic Changes Vegetations on valve closure lines Destruction and perforation of valve leaflet Rupture of chordae tendinae, intraventricular septum, papillary muscles Valve ring abscess Myocardial abscess Conduction abnormalities

30. Pathologic Changes Kidney Immune complex glomerulonephritis Emboli with infarction, abscess Aortic mycotic aneurysms

31. Pathologic Changes Splenic enlargement, infarction Septic or bland pulmonary embolism Skin Petechiae Osler nodes: diffuse infiltrate of neutrophils, and monocytes in the dermal vessels with immune complex deposition. Tender and erythematous Janeway lesions: septic emboli with bacteria, neutrophils and S/C hemorrhage and necrosis. Blanching and non-tender. Palms and soles

32. MUSCULOSKELETAL Vertebral osteomyelitis - rare. Osteomyelitis -S. aureus endocarditis . Acute septic arthritis

34. Splinter Hemorrhages Subungal hemorrhages that extend the entire length of the nail or are primarily located at the proximal end of the nail (near the cuticle) are like due to trauma.Subungal hemorrhages that extend the entire length of the nail or are primarily located at the proximal end of the nail (near the cuticle) are like due to trauma.

35. Osler’s Nodes

36. Janeway Lesions

37. Septic emboli with hemorrhage and infarction due to acute S. aureus endocarditis

38. Roth spots

39. Enlargement of the spleen is noted in 15 to 50 percent of patients and is more common in subacute IE of long duration.

41. Duke’s v/s modified dukes Duke’s sensitivity -76 % in western Major deficiency is inability to diagnose BCNE Major additions in modified dukes includes Q fever serology, staphylococcal bacteremia in the absence of other primary focus as major criteria, serological evidence of other organism consistent with endocarditis as minor criteria.

42. Modified Duke Criteria

44. Rejected IE If an alternative diagnosis is established, If symptoms resolve and do not recur with 4 days of antibiotic therapy, or If surgery or autopsy after 4 days of antimicrobial therapy yields no histologic evidence of endocarditis.

45. Possible IE Illnesses not classified as definite endocarditis or rejected When either one major and one minor criteria or three minor criteria are identified.

46. St Thomas modifications From the Division of Infection, United Medical and Dental School,St. Thomas’ Hospital, London, United KingdomLAMAS & EYKYN et al Inclusion of ESR , CRP, Presence of newly diagnosed clubbing, splenomegaly and microhematuria, as minor criteria Increases sensitivity by 10 % More appropriate in Indian patients

47. St Thomas modifications From the Division of Infection, United Medical and Dental School,St. Thomas’ Hospital, London, United Kingdom Pathologically proven yet culture negative Endocarditis 21 % were classified definite by Original Duke’s 32 % were definite by modified Duke’s 62 % were definite by St Thomas modification

48. Blood Cultures in IE 3 separate venepunctures during one hour period at least 10 ml blood before giving antibiotics. Adherence to above practice yields positive culture in 90 % But at least 30 % are prescribed antibiotics before taking culture. Sterile culture ---western =2.5 to 31% ---Indian = 48 to 54 %

49. Blood Cultures MULTIPLE BLOOD CULTURES BEFORE EMPIRIC THERAPY If not critically ill 3 blood cultures over 12-24 hour period ? Delay therapy until diagnosis confirmed If critically ill 3 blood cultures over one hour No more than 2 from same venepuncture Relatively constant bacteremia

50. “Culture Negative” IE Less common with improved blood culture methods Special media required Brucella, Mycoplasma, Chlamydia, Histoplasma, Legionella, Bartonella Longer incubation may be required HACEK Coxiella burnetii (Q Fever), Trophyrema whipplei will not grow in cell-free media

51. Use of Echo in Diagnosis of IE Native Valves-ACC Guidelines: Detection/characterization of valvular lesions Detection of vegetations and characterization of lesions in patients with CHD Detection of associated abnormalities Reevaluation studies in complex IE Evaluation of patients with high suspicion of culture-negative IE

52. Use of Echo in Diagnosis of IE Prosthetic Valves-ACC Guidelines: Detection/characterisation of valvular lesions Detection of associated abnormalities Reevaluation in complex IE Evaluation of suspected IE and negative cultures Evaluation of persistent fever without known source

53. Typical echo features Oscillating intracardiac mass on a valve or supporting structure or device or in the path of a regurgitant stream Abscess New partial dehiscence of prosthetic valve New valvular regurgitation

54. Echo is useful in predicting complications based on the size of the vegetation, mobility , extent,& consistency, either embolisation or destruction. Vegetations greater than 10 mm often embolise

55. TTE v/s TEE TTE – Initial echo. Sensitive in VSD and aortic valve repair. vegetation above AV or suture site TEE- - Can detect structure upto 1 mm Pulmonic and prosthetic valve lesion aare better visualised Sensitivity 81- 100% Specificity – 91 to 100%

56. Use of Echo in Diagnosis of IE TEE: Prosthetic valves Poor visualization on TTE and high suspicion Detection of associated complications Preoperative Reevaluation in complex IE

57. Other tests Electrocardiogram Conduction delays Ischemia or infarction Chest X-ray Septic emboli in right-sided IE Valve calcification CHF

58. Microbiological advances to increase culture yeild In patients with previous antibiotic therapy the yeild of blood culture can be enhanced by diluting the culture broth and adding sodium polyanetholsulfonate or a dedicated adsorbant resin. Atypical fastidious growing organisms are subcultured on Chocolate agar

59. Serology in IE Serology Coxiella burnetii – endocarditis presents only during chronic infection with coxiella Bartonella Brucella Legionella Chlamydophila

60. Molecular diagnostic techniques in IE PCR RT PCR Proteomics ( protein signatures of the organism used to identify the pathogens)

61. Molecular diagnostic techniques in IE PCR useful in Coxiella burnetii Tropheryma whipplei Bartonella henselae

62. Procalcitonin 116 amino acid peptide No known hormonal activity Under normal metabolic conditions, PCT is only present in the C cell of the thyroid gland In sepsis it is released to circulation Values exceeding 2.3 ng/ml in a suspected case of IE has a sensitivity of 81 %& specificity of 85 %. More valuable than CRP in Sepsis

63. Treatment of IE Native vs. Prosthetic Valve Bactericidal therapy is necessary Eradication of bacteria in the vegetation May be metabolically inactive (stationary phase) May need higher concentrations of antimicrobial agents

64. Antimicrobial Therapy Blood culture become sterile within 2 days Fever resolves in 4 to 7 days If fever persists despite 7 days of antibiotics evaluate for paravalvular or extracardiac abscess Combination therapy most important for Shorter course regimens Enterococcal endocarditis Prosthetic valve infections

65. Streptococci susceptible to pencillin

71. NVE Fungal Amphotericin Fluconazole Caspofungin, little data Surgery usually necessary 1-2 weeks into treatment

72. Prosthetic Valve IE Staphylococci most common Coagulase negative staphylococci Enterococcus Nutritonally variant streptococci Fungi

73. OTHER ORGANISMS Streptococcus pneumoniae Penicillin if sensitive- can be treated with intravenous penicillin ceftriaxone (2 g/d as a single dose), or cefotaxime (at a comparable dosage). Infection caused by penicillin resistant strains hould be treated with vancomycin.

74. P. aeruginosa endocarditis is treated with an antipseudomonal penicillin (ticarcillin or piperacillin) and high doses of tobramycin (8 mg/kg per day in three divided doses). Endocarditis caused by Enterobacteriaceae is treated with a potent beta-lactam antibiotic plus an aminoglycoside.

75. Corynebacterial endocarditis is treated with penicillin plus an aminoglycoside (if the organism is susceptible to the aminoglycoside) or with vancomycin Therapy for Candida endocarditis consists of amphotericin B plus flucytosine and early surgery; long-term suppression with fluconazole is also used.

76. Empirical Therapy Therapy without culture data (i.e., before culture results are known or when cultures are negative). For acute endocarditis in an injection drug user should cover methicillin-resistant S. aureus and gram-negative bacilli. The initiation of treatment with vancomycin plus gentamicin immediately after blood is obtained for cultures covers these as well as many other potential causes.

77. In culture-negative -marantic endocarditis must be excluded and fastidious organisms sought serologically. In the absence of prior antibiotic therapy, it is unlikely to be due to S. aureus, coagulase-negative staphylococcal, or enterococcal. Blood culture–negative subacute native valve endocarditis is treated with ceftriaxone plus gentamicin. These two antimicrobials plus vancomycin should be used if prosthetic valves are involved.

78. Serologic abnormalities (e.g., erythrocyte sedimentation rate, rheumatoid factor) resolve slowly and do not reflect response to treatment. Vegetations become smaller with effective therapy, but at 3 months after cure half are unchanged and 25% are slightly larger.

80. Prophylactic Therapy -- Current Scenario

81. 1997 American Heart Assoc. Guidelines: Endocarditis Prophylaxis Recommended:    High-risk category       Prosthetic cardiac valves, including bioprosthetic and homograft valves       Previous bacterial endocarditis       Complex cyanotic congenital heart disease (eg, single ventricle states, transposition of the great arteries, tetralogy of Fallot)       Surgically constructed systemic pulmonary shunts or conduits    Moderate-risk category       Most other congenital cardiac malformations (other than above and below)      Acquired valvar dysfunction (eg, rheumatic heart disease)       Hypertrophic cardiomyopathy       Mitral valve prolapse with valvar regurgitation and/or thickened leaflets Endocarditis Prophylaxis Not Recommended:   Negligible-risk category (no greater risk than the general population)      Isolated secundum atrial septal defect       Surgical repair of atrial septal defect, ventricular septal defect, or patent ductus arteriosus (without residua beyond 6 mo)       Previous coronary artery bypass graft surgery       Mitral valve prolapse without valvar regurgitation1       Physiologic, functional, or innocent heart murmurs1      Previous Kawasaki disease without valvar dysfunction      Previous rheumatic fever without valvar dysfunction      Cardiac pacemakers (intravascular and epicardial) and implanted defibrillators Memorize this table. Kidding.Memorize this table. Kidding.

82. 1997 AHA Guidelines Assumptions: Bacteremia with organisms known to cause IE occurs in assoc. with invasive dental/GI/GU procedures Antibiotic prophylaxis was proven effective in animals Antibiotic prophylaxis thought to be effective in human

83. Reasons for 2007 Revision IE more likely due to frequent exposure to random bacteremias from daily activities than from bacteremia during dental/GI/GU procedure Prophylaxis may prevent only small number of cases of IE, even if 100% effective Risk of antibiotic-assoc. adverse events exceeds the benefit, if any, from prophylaxis To reduce the risk of bacteremia from dental procedure: maintaining good oral health and hygiene is more important than Antibiotic prophylaxis

84. Frequency of Transient Bacteremia Tooth extraction 10-100% Periodontal surgery 36-88% Teeth cleaning 40% Tooth brushing, 20-68% Using wooden toothpicks 20-40% Chewing food 7-51%

85. Risk of IE from dental procedures? No prospective, randomized, placebo-controlled studies exist on efficacy of Antibiotic prophylaxis in preventing IE after dental procedure 2 wks is reasonable time period2 wks is reasonable time period

86. 2007: Who gets prophylaxis? Only patients with the highest risk of adverse outcomes (heart failure, surgery, death) from endocarditis: 1. Prosthetic cardiac valve 2. Previous IE 3. Cardiac transplant recipients who develop cardiac valvulopathy 4. Congenital Heart Disease This is the “HIGH” risk category from 1997This is the “HIGH” risk category from 1997

87. Which categories of Congenital Heart Disease? Unrepaired cyanotic CHD Tetralogy of Fallot, Transposition of Great Arteries, including palliative shunts and conduits Completely repaired congenital heart defect with prosthetic material or device during 1st 6 months after surgery Repaired CHD with residual defects at or near a prosthetic patch/device (which inhibit endothelialisation)

88. What about “Moderate-Risk” Pts? 1997’s “Moderate Risk” Category NO LONGER gets prophylaxis: MVP with regurg and/or thickened leaflets Hypertrophic cardiomyopathy Acquired Valvular Dysfunction (eg rheumatic heart disease)

89. Dental Procedures “If it bleeds, give prophylaxis” High-risk pts undergoing all dental procedures that involve manipulation of gingival tissues OR periapical region of teeth OR perforation of oral mucosa i.e. biopsies, suture removal, placing orthodontic bands NO PROPHYLAXIS: Xray, anesthetic injections, fluoride treatments Shedding of deciduous teeth Placement/adjustment of removable prosthodontic or orthodontic appliances “quote” from Vance Fowler, IE expert at Duke, IDSA review course 9/08“quote” from Vance Fowler, IE expert at Duke, IDSA review course 9/08

90. Prophylaxis for Dental Procedures Goal: cover Strep Viridans Single dose, 30-60 min prior to procedure

91. What about resistant Strep Viridans? Quinolones or IV Vancomycin not recommended for prophylaxis due to concern of creating new drug resistance

92. Respiratory Tract Procedures No published data linking resp tract procedures and IE.... Consider prophylaxis for High-risk pts undergoing Invasive Procedure in resp tract with incision or biopsy of resp mucosa: Tonsillectomy Adenoidectomy Bronchoscopy WITH biopsy (not for BAL alone) Resp tract procedure to drain abscess or empyema

93. GI/GU Procedures No published data linking GI/GU procedures and IE.... NO prophylaxis for GI/GU procedures

94. Procedures on Infected Skin/Skin Structure, or Msk Tissue In patients who are HIGH-risk for IE: The antibiotic regimen given to treat the skin or musculoskeletal infection should contain an Anti-staphylococcal Pencillin or cephalosporin If unable to take PO or Pencillin-allergic: Clindamycin or Vancomycin

95. Summary: IE prophylaxis Need high-risk patient PLUS high-risk procedure High-risk pts: 1. Prosthetic cardiac valve 2. Previous IE 3. Cardiac transplants with valvulopathy 4. Congenital Heart Disease High-risk procedures: Dental: “If it bleeds, give prophylaxis” Respiratory: Consider if pt will be cut or biopsied GI/GU: never

96. No Prophylaxis Endotracheal intubation Cardiac cath/stent Pacer/ICD implantation OGD, Colonoscopy Barium Enema TEE Incision/Bx of surgically scrubbed skin Circumcision Vaginal delivery Hysterectomy