Infective Endocarditis

1. Infective Endocarditis Dr Ahmed Qamruddin Consultant Microbiologist

2. Definition • Infective Endocarditis (IE): an infection of the heart’s endocardial surface • Main Classification: • Native Valve IE • Prosthetic Valve IE • Additional Consideration • Intravenous drug abuse (IVDA) IE • Nosocomial IE

3. Acute Affects normal heart valves Rapidly destructive Metastatic foci Commonly Staph. If not treated, usually fatal within 6 weeks Caused by virulent organisms Subacute Often affects damaged heart valves Indolent nature If not treated, usually fatal by one year Caused by less virulent organisms Further Classification

4. Infected vs Normal Valve

5. Epidemiology • Incidence difficult to ascertain and varies according to location • Much more common in males than in females • May occur in persons of any age and increasingly common in elderly & IVDU • Mortality ranges from 20-30%

6. Pathophysiology • Turbulent blood flow within the heart - most often (but not always) – patient has risk factors for this • Turbulent blood flow disrupts valve surface (endocardium) to produce suitable (sticky) site for bacterial attachment • Platelet deposition + fibrin may lead to non-bacterial thrombus or vegetation • Bacteraemia – delivers organisms to the damaged (sticky) endocardial surface resulting in adherence & colonisation • Eventual invasion of valve leaflets results in infected vegetation (sheath of fibrin & platelets, ideal conditions for further bacterial multiplications, protection from polymorphs)

7. Pathophysiology

8. Turbulent Blood Flow • Rheumatic fever history • Old age – calcified valves • Mitral valve prolapse with regurgitation • Prosthetic heart valves • Congenital defects / any structural defect • Cardiac surgery • Central lines • Pacemakers • Intravenous drug abuse Varying predisposing conditions exist, but in over 50% of cases, no identified valvular lesion can be found.

9. Summary-Risk Factors

10. Causes of Bacteraemia • Brushing teeth • Eating/chewing • Dental work • IV lines (colonised/infected) • IV drug use • Infected site/abscess alpha-haemolytic streptococci from oral flora Staphylococcus aureus from skin/nose Strep. pneumoniae, S.aureus

11. Causes of Bacteraemia

12. Infecting Organisms • Common bacteria • Alpha haem streptococci (viridans – S. mitis, S. sanguis) SUBACUTE • Enterococci (E. faecalis) SUBACUTE • Coagulase Negative Staphylococci – PROSTHETIC VALVES, SUBACUTE • Less common bacteria • S. aureus ACUTE • B-Haemolytic streptococci ACUTE • Streptococcus pneumonia • Not so common bacteria • Fungi • Pseudomonas / Coliforms • HACEK group organisms

13. Infecting Organisms • Streptococci 60-80% • Alpha-haemolytic Streptococci (viridans – S. mitis, S. oralis) 30-40% (subacute) • Enterococci (E. faecalis) 5-18% (subacute) • Beta-haemolytic streptococci (e.g. Gp A Strep) – rare (acute) • Staphylococci 20-35% • S. aureus 10-27% (acute) • Coagulase negative staphylococci (Staph epidermidis) 1-3 % (mainly prosthetic valve risk, subacute) • Fungi • Candida – IVDU at risk (usually indolent) • Aspergillus – rare • Gram-negative bacteria – rare • Culture-negative endocariditis HACEK, Q-fever – cases do occur, subacute

14. Infecting Organisms

15. Acute High grade fever and chills SOB Arthralgias/ myalgias Abdominal pain Pleuritic chest pain Back pain Subacute Low grade fever Anorexia Weight loss Fatigue Arthralgias/ myalgias Abdominal pain N/V Symptoms The onset of symptoms is usually ~2 weeks or less from the initiating bactaeremia

16. Signs • Fever • Heart murmur • Nonspecific signs – petechiae, subungal or “splinter” hemorrhages, clubbing, splenomegaly, neurologic changes • More specific signs - Osler’s Nodes, Janeway lesions, and Roth Spots

17. Petechiae • Nonspecific • Often located on extremities • or mucous membranes dermatology.about.com/.../ blpetechiaephoto.htm Harden Library for the Health Sciences www.lib.uiowa.edu/ hardin/ md/cdc/3184.html Photo credit, Josh Fierer, M.D. medicine.ucsd.edu/clinicalimg/ Eye-Petechiae.html

18. Splinter Hemorrhages • Nonspecific • Nonblanching • Linear reddish-brown lesions found under the nail bed • Usually do NOT extend the entire length of the nail

19. Osler’s Nodes American College of Rheumatology webrheum.bham.ac.uk/.../ default/pages/3b5.htm www.meddean.luc.edu/.../ Hand10/Hand10dx.html • More specific • Painful and erythematous nodules • Located on pulp of fingers and toes • More common in subacute IE

20. Janeway Lesions • More specific • Erythematous, blanching macules • Nonpainful • Located on palms and soles

21. Blood Cultures • Blood Cultures • Minimum of three blood cultures (ideally spread over 24 hrs) • Three separate venipuncture sites ideally • Obtain correct volume of blood for culture bottles • Positive Result • 1 set gives 90% sensitivity, remaining 2 sets add 8% • Multiple same cultures are important in confirming significance, especially for less typical organisms • Negative Result • Prior antibiotic therapy • ‘Culture negative endocarditis’ – fastidous orgs / non-culturable • May support a non-endocarditis patient diagnosis

22. Blood Cultures • Always need to get full identification of bacteria from positive blood cultures in suspected endocarditis • Full sensitivity testing • Need full MIC (minimum inhibitory concentration) for Penicillin • Liaison with Lab/microbiologist in cases where endocarditis suspected/diagnosed

23. Additional Tests • CBC • ESR and CRP • Complement levels (C3, C4, CH50) • RF • Urinalysis • Baseline chemistries and coags

24. Imaging • Chest x-ray • Look for multiple focal infiltrates and calcification of heart valves • ECG • Rarely diagnostic • Look for evidence of ischemia, conduction delay, and arrhythmias • Echocardiography

25. Indications for Echocardiography • Transthoracic echocardiography (TTE) • First line if suspected IE • Native valves • Transesophageal echocardiography (TEE) • Prosthetic valves • Intracardiac complications • Inadequate TTE • Fungal or S. aureus or bacteraemia

26. Making the Diagnosis • Pelletier and Petersdorf criteria (1977) • Classification scheme of definite, probable, and possible IE • Reasonably specific but lacked sensitivity • Von Reyn criteria (1981) • Added “rejected” as a category • Added more clinical criteria • Improved specificity and clinical utility • Duke criteria (1994) • Included the role of echocardiography in diagnosis • Added IVDA as a “predisposing heart condition”

27. Duke Criteria

28. Modified Duke Criteria Clinical criteria diagnosis - 2 major criteria OR 1 major and 3 minor criteria OR 5 minor criteria

29. Modified Duke Criteria • Definite IE • Microorganism (via culture or histology) in a valvular vegetation, embolized vegetation, or intracardiac abscess • Histologic evidence of vegetation or intracardiac abscess • Possible IE • 2 major • 1 major and 3 minor • 5 minor • Rejected IE • Resolution of illness with four days or less of antibiotics

30. Treatment • Parenteral (IV) antibiotics • High serum concentrations to penetrate vegetations • Prolonged treatment to kill dormant bacteria clustered in vegetations • Surgery • Intracardiac complications/paravalve abscess • Surveillance blood cultures

31. Treatment – Empiric

32. Treatment - Specific • Modify empiric therapy once cultures/sensitivities known • Long duration 4-6 weeks Rx is required • Refer to Trust Guidelines / BSAC Working Party Guidelines (2004) • Liaise with Microbiologist • Liaise with Cardiac Surgeon if needed • Monitor response to treatment (clinical, CRP, ECHO) & look for complications

33. Viridans Streptococci (specific treatment)

34. Complications • Four etiologies • Embolic • Local spread of infection • Metastatic spread of infection • Formation of immune complexes – glomerulonephritis and arthritis

35. Complications

36. Embolic Complications • Occur in up to 40% of patients with IE • Predictors of embolization • Size of vegetation • Left-sided vegetations • Fungal pathogens, S. aureus, and Strep. Bovis • Incidence decreases significantly after initiation of effective antibiotics

37. Embolic Complications • Stroke • Myocardial Infarction • Fragments of valvular vegetation or vegetation-induced stenosis of coronary ostia • Ischemic limbs • Hypoxia from pulmonary emboli • Abdominal pain (splenic or renal infarction)

38. Septic Pulmonary Emboli http://www.emedicine.com/emerg/topic164.htm

39. Septic Retinal Embolus

40. Local Spread of Infection • Heart failure • Extensive valvular damage • Paravalvular abscess (30-40%) • Most common in aortic valve, IVDA, and S. aureus • May extend into adjacent conduction tissue causing arrythmias • Higher rates of embolization and mortality • Pericarditis • Fistulous intracardiac connections

41. Local Spread of Infection Acute S. aureus IE with perforation of the aortic valve and aortic valve vegetations. Acute S. aureus IE with mitral valve ring abscess extending into myocardium.

42. Metastatic Spread of Infection • Metastatic abscess • Kidneys, spleen, brain, soft tissues • Meningitis and/or encephalitis • Vertebral osteomyelitis • Septic arthritis

43. Pre-antibiotic era, infective endocarditis was invariably fatal (acute – within 2 weeks, or subacute – within a year) Post-antibiotic era, there is still significant mortality (20-40%), but can reduce by early diagnosis and optimal antibiotic/medical/surgical treatment Prognostic Factors

44. Female S. aureus Vegetation size Aortic valve Prosthetic valve Older age Diabetes mellitus Low serum albumen Apache II score Heart failure Paravalvular abscess Embolic events Poor Prognostic Factors

45. Prevention of Endocarditis NICE Guidance 2008 - prophylaxis generally NOT needed • There is no consistent association between having an interventional procedure, dental or nondental, and the development of IE. • Regular toothbrushing almost certainly presents a greater risk of IE than a single dental procedure because of repetitive exposure to bacteraemia with oral flora. • The clinical effectiveness of antibiotic prophylaxis is not proven. • Antibiotic prophylaxis against IE for dental procedures may lead to a greater number of deaths through fatal anaphylaxis than a strategy of no antibiotic prophylaxis • And is not cost effective.

46. Prevention of Endocarditis

47. Summary • IVDA and the elderly are at greatest risk of developing IE. • The signs and symptoms of IE are nonspecific and varied. • A thorough but timely evaluation (including blood cultures, adjunct labs, and an echo) is crucial to accurately diagnose and treat IE. • Beware of life-threatening complications.

48. Acknowledgments • This presentation has been adapted from an original presentation by Christine Criscuolo Higgins, MD CHRISTUS Santa Rosa FMRP, San Antonio, Texas, January 10th, 2006