Infective Endocarditis

1. Infective Endocarditis Dr. Meral SÖNMEZOĞLU InfectousDiseasesDepartment YEDİTEPE UNIVERSITY HOSPITAL

2. LearningObjectives • Recognize the risk factors, signs, and symptoms of infectious endocarditis. • Understand the many approaches to diagnosing infectious endocarditis. • Appreciate the necessity of rapid treatment. • Anticipate possible complications. • Know the indications for prophylaxis of infective endocarditis

3. InfectiveEndocarditis • Infective endocarditis (IE) is a deadly disease. • Despite improvements in its management, IE remains associated with high mortalityand severe complications

4. Definition • IE should be suspected in a variety of very different clinical situations. • It may present as an acute, rapidly progressiveinfection, but also as a subacute or chronic disease with low-gradefever and non-specific symptoms that may mislead or confuse initialassessment.

5. Definition • Up to 90% of patients present with fever, often associated with systemic symptoms of chills, poor appetite and weight loss. • Heart murmurs are found in up to 85% of patients. • Up to 25% of patients haveembolic complications at the time of diagnosis. Therefore IE has to besuspected in any patient presenting with fever and embolic phenomena.

6. Definition • Infectious Endocarditis (IE): an infection of the heart’s endocardial surface • Classified into four groups: • Native Valve IE • Prosthetic Valve IE • Intravenous drug abuse (IVDA) IE • Nosocomial IE (HCA- IE) 1/3

7. Sites of lesions • Mitral Valve: 85% (Left atrium/ventricle) • Common site for Strep viridans group • Aortic valve: 55% (Left ventricle) • Emboli would effect systemic organs brain, kidneys, spleen • Tricuspid valve: 20% (Right atrium/ventricle) • Common site for IV drug users (Staph. spp) • Emboli to lung • Pulmonary valve: 1% (Right ventricle)

8. European Heart Journal (2015)

9. Classification • Nativevalveendocarditis (NVE), acuteandsubacute • Prostheticvalveendocarditis (PVE),earlyandlate • Intravenousdrugabuse (IVDA) endocarditis • Other terms commonly used to classify types of IE include pacemaker IE and nosocomial IE (NIE).

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

11. Acute Rapid progression of symptoms Less than 6 weeks duration Significant systemic signs/symptoms Fever Elevated systemic WBC/ left shift Subacute Slower, more chronic progression of symptoms Low grade fevers Vague clinical signs/symptoms weakness, anorexia, malaise,etc. Further Classification

12. Acute NVE • Frequently involves normal valves and usually has an aggressive course. • Rapidly progressive illness in persons who are healthy or debilitated • Virulentorganisms, S aureus and group B streptococciare typically the causative agents

13. Subacute NVE • Typically affects only abnormal valves. • Its course, even in untreated patients, is usually more indolent than that of the acute form and may extend over many months. • Alpha-hemolytic streptococci or enterococci, usually in the setting of underlying structural valve disease

14. PVE • Diagnosis is more difficult in PVE than in NVE. • Clinical presentationis frequently atypical, particularly in the early postoperative period,in which fever and inflammatory syndromes are common in the absence of IE. • Persistent fever should trigger the suspicionof PVE.

15. PVE • As in NVE, diagnosis of PVE is based mainly on the results ofechocardiography and blood cultures. However, both are more frequently negative in PVE. • Although TOE is mandatory in suspectedPVE, its diagnostic value is lower than in NVE.

16. PVE • A negativeechocardiogram is frequently observed in PVE and does not ruleout the diagnosis, but identification of a new periprosthetic leak isa major criterion • CT or nuclear imaging is useful • In PVE, staphylococcal and fungal infections are more frequentand streptococcal infection less frequent than in NVE.

17. PVE • Staphylococci, fungi and Gram-negative bacilli are the main causes of earlyPVE, • Staphylococci, oral streptococci, S. bovis and enterococcimost frequent organismsof latePVE (community-acquiredinfections). • Staphyloccoci and enteroccociare the most commonagents in prosthetic valve implantation endocarditis.

18. PVE • The Duke criteria arehelpful for the diagnosisof NVE (70–80%), but are less useful in PVE • Nucleartechniques, particularly 18F-FDG PET/CTuseful for the diagnosis of PVE • An algorithm for evaluation of patients with suspected PVE, including echocardiography and PET/CT has been suggested

19. Early PVE • Early PVE occurs within 60 days of valve implantation. • Traditionally, • coagulase-negative staphylococci, • gram-negative bacilli, and • Candida species have been the common infecting organisms.

20. Late PVE • Early PVE is defined as IE occurring within 1 year of surgery • LatePVE as IE occurring beyond 1 year, because of significant differences between the microbiological profiles

21. Pathophysiology • Turbulent blood flow disrupts the endocardium making it “sticky” • Bacteremia delivers the organisms to the endocardial surface • Adherence of the organisms to the endocardial surface • Eventual invasion of the valvular leaflets

22. Pathophysiology • Formation of Non-Bacterial Thrombotic Endocarditis(NBTE) on surface of cardiac valve or site ofendothelialdamage • Turbulent blood flow from certain congenital cardiac lesionstraumatizesendothelium • Traumatized endothelium predisposed to deposition ofplatelets and fibrin on endothelial surface resulting in NBTE • Bacteremia with potentially pathogenic organism • Adherence of bacteria in bloodstream to NBTE • Proliferation of bacteria within a vegetation

23. Pathophysiology

25. Infectious Endocarditis Affecting the Mitral Valve: Destruction of the Mitral Valve Fibrin Due to Haemophilus parainfluenzae Bacterial Infection

27. Pathogenesis • Multiple independent pathophysiological processes • “Trauma” of the heart surfaces • Platelet/fibrin deposition over traumatized tissue (non-bacterial thrombotic endocarditis) • “Bacteremia” subsequent infection of the platelet/fibrin deposition (Bacterial endocarditis) • Bacterial multiplication (10 9,10cfu/gram of tissue)

28. Causes of Bacteremia • Dental: • Procedures -Flossing/brushing • Diagnostic Procedures • Respiratory • Bronchoscopy • G.I. • Barium enema • Colonoscopy • Genitourinary • Prostatectomy

29. Epidemiology • Incidence difficult to ascertain and varies according to location • 3-9:100.000 in industrialcountries • Occurs in 1:1000 hospital admission • Much more common in males than in females (2:1) • May occur in persons of any age and increasingly common in elderly • Mortality ranges from 20-30%

30. Risk Factors • Intravenous drug abuse • Artificial heart valves and pacemakers • Acquired heart defects • Calcific aortic stenosis • Mitral valve prolapse with regurgitation • Congenital heart defects • Intravascular catheters

31. Risk Factors • Rheumatic heart disease • Currently accounts for 20-25% of cases • Prosthetic heart valves • 12-33% of cases: Staph common if IE occurs within 1 year of surgery; surgery required to replace infected material • IV drug use • Staph spp. most commonly isolated • Intravenous catherization/shunt procedures • Congenital heart defects • patent ductusarteriosus, intraventricular shunts, etc • Degenerative cardiac lesions

32. Infecting Organisms • Common bacteria • S. aureus • Streptococci • Enterococci • Not so common bacteria • Fungi • Pseudomonas • HACEK

33. Streptococci • Alpha-hemolyticMostcommon • Beta-hemolyticUncommon • EnterococciRare • PneumococciRare • Staphylococci • S. aureusSecondmostcommon • Coagulase negative Uncommon, but increasing • Gram-NegativesAllRare • Enterics, Pseudomonasspecies, Haemophilus, Actinobacillus,Cardiobacterium, Eikenella, Kingella, Neisseria sp • Fungi • CandidaspeciesUncommon • OthersRare

34. Infecting Organisms • Overall, S aureus infection is the most common cause of IE, including PVE, acute IE, and IVDA IE. • Approximately 35-60.5% of staphylococcal bacteremias are complicated by IE. • More than half the cases are not associated with underlying valvular disease.

35. IE: Infecting organisms • Bacterial(80-90% of all causes due to strep & staph species) • Streptococci: 55-60% • Viridans strep: Strep species normally found in mouth • Strep sanguis, oralis, salivarius, or mutans • Rarely caused by Group A, B, C, strep

36. IE: Infecting organisms • Staph. species: accounts for 20-35% of all bacterial causes • Staph aureus: (coagulase positive staph) Coagulase is an enzyme capable of causing serum proteins to clot. • A. Most common bacteria isolated from IV drug users • B. Most common staph species isolated from I.E. infections • C. Mortality is approximately 40% • D. Therapy duration based on presence/absence of prosthetic material and antibiotic sensitivity

37. IE: Infecting organisms • Staph epidermidis: (coagulase-negative) • A. Most common staph species in patients with prosthetic valves and in neonates • B. Often presents as subacute IE (SBE) • Gram Negative Bacteria • HACEK group: Hemophilus spp., Actinobacillusspp, Cardiobacteriumspp, Eikenellaspp, Kingella spp. • Miscellaneous Gram Negative Organisms: • Typical gram negative bacilli (E. coli, Klebsiella, etc) • A. Frequently part of polymicrobial infections • B. IV drug users or patients with prosthetic material • C. High mortality rate: >65%

38. 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 bacteremia

39. 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

40. 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

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

42. Splinter Hemorrhages

43. 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

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

46. Roth spot •“White-centered" hemorrhages, originally described in patients with bacterial endocarditis. •Non-specific for endocarditis, but discovering them in a patient who has other suggestive features of endocarditis constitutes strong support for the diagnosis

47. TheEssentialBlood Test • Blood Cultures • Minimum of three blood cultures1 • Three separate venipuncture sites • Obtain 10-20mL in adults and 0.5-5mL in children2 • Positive Result • Typical organisms present in at least 2 separate samples • Persistently positive blood culture (atypical organisms) • Two positive blood cultures obtained at least 12 hours apart • Three or a more positive blood cultures in which the first and last samples were collected at least one hour apart

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

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

50. 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 bacteremia