CVS infective endocarditis. .pptx

Infective endocarditis power point

1. INFECTIVE ENDOCARDITIS

2. CONTENTS Introduction Etiology Pathogenesis Clinical manifestations and complications Diagnosis Treatment Prognosis

3. INTRODUCTION The prototypic lesion of infective endocarditis, the vegetation, is a mass of platelets, fibrin, microcolonies of microorganisms and scant inflammatory cells Infection most commonly involves heart valves but may also occur on low-pressure side of ventricular septal defect , on mural endocardium damaged by aberrant jets of blood or foreign devices, or on intracardiac devices themselves

4. In 1674, Lazaire Riviere first described the gross autopsy findings of IE in his monumental work Opera medica universa . In 1885, William Osler presented the first comprehensive description of endocarditis in English. Lerner and Weinstein published about “ Infective Endocarditis in the Antibiotic Era ,” in the New England Journal of Medicine.

5. EPIDEMIOLOGY In developed countries, the incidence of endocarditis ranges from 4 to 7 cases per 100,000 population every year, with a 1- year mortality approaching 40%. The incidence (11.6/100,000) increases in certain areas where IVDAss are common. But such estimates from India are not available. The median age of patients has gradually increased from the fourth decade in early antibiotic era to sixth and seventh decade recently. In the Indian scenario; still it is common in younger age groups.

6. RISK FACTORS Valvular heart disease – MR with degenerative MVP m/c, 2 nd m/c is AR. Congenital heart disease – M/c is VSD. Prosthetic valves CIED ( Cardiovascular implantable electronic devices) IV drug use Chronic IV access H/O invasive dental procedures. Diabetes, malignancy, renal failure on hemodialysis.

7. CLASSIFICATION According to temporal evolution of disease, Acute Subacute According to location of infection Native valve endocarditis Prosthetic valve endocarditis Device related endocarditis Right sided endocarditis

8. Acute Endocarditis – De v el o ps over a peri o d o f days , rapid l y dam ages ca r diac structures and seeds extracardiac sites. Presents as high grade fever, fatigue and tachycardia. Usually caused by S. aureus, Beta hemolytic streptococci and Pneumococci . Subacute Endocarditis – Develops over week to months. Indolent course Damages cardiac structures slowly. Rarely metastasizes. Presents with vague constitutional symptoms. Usually caused by Viridans streptococci, Enterococci, CoNS and the HACEK group.

9. Native valve endocarditis (NVE) – Acute NVE frequently involves normal valves. Virulent such as S aureus and group B streptococci, are typically the causative agents of this type of endocarditis. Subacute NVE typically affects only abnormal valves. Alpha- hemolytic streptococci or enterococci are usual causative agents Health care associated NVE usually caused by S. aureus , CONS and Enterococci , may have either nosocomial onset(55%) or a community onset (45%); community onset cases develop in patients who have had extensive contact with the health care system over preceding 90 days.

10. Prosthetic Valve Endocarditis (PVE) – B e tween 1 6 t o 3 % o f a l l cas e s o f endoca r di t i s occu r in prosthetic valves. Risk o f infection h i ghes t i n fi r s t 6 t o 12 mont h s o f valve replacement. PVE arising within 2 months of valve surgery is generally nosocomial, the result of intraoperative contamination of prosthesis or a bacteremic postoperative complication. This nosocomial origin is reflected in the primary microbial causes; S. aureus, CoNS , facultative gram-negative bacilli, diptheriods and fungi. Infection between 2-12 months is mostly due to CoNS represents delayed onset nosocomial infection The portal of entry and organisms causing cases beginning after 12 months after surgery are similar to those in community-acquired NVE .

11. Device – related Endocarditis I E r e la t ed t o Ca r di o vasc u lar Implan t able E lect r onic De v ices involves the device or the endothelium point of device contact. One-third of cases of CIED endocarditis present within 3 months after implantation or manipulation, one-third present 4-12 months and one third present after 1 year Mostly caused by S. aureus and CoNS. Risk fa c to r s a r e Renal failu r e , D M , he m a toma at t h e s ite of implantation.

12. Right – sided Endocarditis Mostly associated with IV drug use. S. aureus is the most common causative organism. In addition to usual causes of endocarditis, these cases can be due to Pseudomonas aeruginosa and candida species, and sporadiac cases can be caused by unusual organisms such as bacillus, lactobacillus, and corynebacterium species Tricuspid valve is most commonly affected. Pulmonary valve may also be involved.

13. ORGANISMS causing IE Streptococcus viridans – Cause native valve infection in RHD pts Beta Hemolytic Streptococci – Acute presentation. Frequent complications. Streptococcus gallolyticus - <10% cases of IE S. aureus – Both NVE and PVE. Acute presentation Coagulase negative staphylococci – Mostly in prosthetic valve. Subacute presentation Enterococcus – A/w CV catheter use. Multi drug resistance. HACEK group – Subacute presentation. Large vegetation. Aerobic gram –ve bacilli – E. coli, Klebsiella, Enterobacter, Pseudomonas Fungi – Candida m/c organism. a/w IV drug use and in prosthetic valve. Surgery needed. Atypical organisms – Coxiella, Bartonella, Brucella, T.whipelli, Legionella -indolent coarse

14. PATHOGENESIS The endothelium, unless damaged, is resistant to infection by most bacteria and to thrombus formation. Endothelial injury ( e.g., at the site of impact of high-velocity blood jets or on the low-pressure side of a cardiac structural lesion) allow either direct infection by virulent organisms or development of an uninfected platelet-fibrin thrombus- a condition called nonbacterial thrombotic endocarditis (NBTE). The thrombus subsequently serves as a site of bacterial attachment during transient bacteremia. The cardiac condition most commonly resulting in NBTE are mitral regurgitation, aortic stenosis, aortic regurgitation, ventricular septal defects and complex congenital heart disease NBTE also arises as result of hypercoagulable state; this phenomenon give rise to the clinical entity of marantic endocarditis(uninfected vegetations seen in patients with malignancy and chronic disease)

15. Organisms enter bloodstream from skin, mucosal surfaces or focal sites of infection. Except for more virulent bacteria (e.g., S.aureus ) that can adhere directly to intact endothelium or exposed subendothelial tissue, microorganism in blood adhere at sites of NBTE O r ganisms exp r es s su r face a dhesins ( MSCRAMMS ) that mediate adherence to NBTE or damaged endothelium. Adherence is facilitated by – Fibronectin binding proteins present on many gram positive organisms; by clumping factor ( a fibrinogen and fibrin binding surface protein) on S. aureus, Fibrinogen binding surface proteins (Fss2), Collagen binding protein (Ace) and Ebp pili in Enterococcus faecalis and, by Glucans or FimA on streptococci.

16. Fibronectin-binding surface proteins are required for S.aureus invasion of intact endothelium; thus these surface protein may facilitate infection of previous normal valves. If resistant to the bactericidal activity of serum and microbicidal peptides released by local platelets, adherent organism profilerate to form dense microcolonies . Organisms deep in vegetations are metabolically inactive (non growing) and relatively resistant to killing by antimicrobial agents. Proliferating surface organisms are shed into the bloodstream continuously.

17. MORPHOLOGY Vegetations on heart valves are classic hallmarks of IE; these are friable, bulky, potentially destructive lesions containing fibrin, inflammatory cells and bacterial or other organisms. The aortic and mitral valves are the most common site of infection, although the valves of the right heart may also involved, particularly in intravenous drug abusers. The vegetations of sub acute endocarditis are associated with less valvular destruction than those of acute endocarditis although the distinction can be subtle. Microscopically the vegetations of subacute of IE typically exhibit granulations tissue at their bases indicative of healing. With time, fibrosis, calcification, and a chronic inflammatory infiltrate can develop.

18. Comparison of the four major forms of vegetative endocarditis The rheumatic fever phase of rheumatic heart disease (RHD) is marked by small, warty vegetations along the lines of closure of the valve leaflets. Infective endocarditis is characterized by large, irregular masses on the valve cusps that can extend onto chordae Nonbaceterial thrombotic endocarditis (NBTE) typically exhibits small,bland vegetation along the line of closure of the leaflets and are loosely attached to the underlying valve Libman -sacks endocarditis has small or medium sized vegetations on either or both side of the valve leaflets

19. PATHOGENESIS OF INFECTIVE ENDOCARDITIS Underlying valvular or non valvular structural abnormality Blood flow turbulence and endothelial damage Fibrin deposition and thrombus formation (NBTE) Bacterial growth in thrombus and formation of dense microcolonies Microorganisms induce further platelet deposition by eliciting tissue factor Fibrin deposition, platelet aggregation and microorganism proliferation together form infected vegetation

20. CLINICAL MANIFESTATIONS The clinical manifestations of endocarditis-other than constitutional symptoms, which probably result from cytokine production arise from damage to intracardiac structures; embolization of vegetation fragments, leading to infection or infraction of remote tissues; and tissue injury due to deposition of circulating immune complexes or immune response to deposited bacterial antigens Fever – m/c symptom but maybe absent in upto 20% cases. Constitutional symptoms like chills, night sweats, headache, malaise, nausea, myalgia, arthralgia. Dyspnea if present is indicative of a severe hemodynamic lesion probably a left sided valvular regurgitation. Orthopnea/ PND indicate onset of heart failure. Pleuritic chest pain may occur due to septic embolization and infarction complicating tricuspid valve IE.

21. CARDIAC MANIFESTATION Although heart murmurs are usually indicative of the predisposing cardiac pathology rather than of endocarditis, valvular damage and ruptured chordae may result in new regurgitant murmurs. In acute endocarditis involving a normal valve, murmurs may be absent initially but ultimately detected in 85% of cases. Congestive heart failure(CHF) develops in 30-40% of patients as a consequence of valvular dysfunction. Heart failure due to aortic dysfunction progress more rapidly than does due to the mitral valve dysfunction. Extension of infection beyond valve leaflets into adjacent annular or myocardial tissue results in perivalvular abscess, which in turn may cause intracardiac fistulae with new murmurs. Abscesses may burrow from aortic valve annulus through epicardium, causing pericarditis or into the upper ventricular septum, where they may interrupt the conduction system, leading to varying degree of heart block.

22. Non cardiac manifestions The classic nonsuppuratice pheripheral manifestations of subacute endocarditis (e.g., janeway lesions) are related to prolonged infection. In contrast, septic embolization mimicking some of those lesions (subungual hemorrhage, osler’s nodes) is common in patients with acute S.aureus endocarditis. Hematogenously seeded focal infection occurs most often in the skin,spleen , kidneys, skeletal system and meninges. Endocarditis caused by S.aureus , vegetations >10mm in diameter, and infection involving the mitral valve, especially anterior leaflet, are independently associated with risk of embolization. Arterial emboli, one half of which precede the diagnosis are clinically apparent in upto 50% of patients Cerebrovascular emboli presenting as a stroke or occasionally as encephalopathy complicate 10-35% of cases of endocarditis. Again one-half of these events precede the diagnosis of endocarditis

23. Other neurological complications include aspectic or purulent meningitis, intracranial hemorrhage due to hemmorhagic infract or ruptured mycotic aneurysms and seizures. ( mycotic aneurysms are focal dilations of arteries occurring at points in the arterty wall that have been weakened by infection in the vasa vasorum or where septic emboli have lodged). Microabscesses in the brain and meninges occur commonly in S.aureus endocarditis Immune complex deposition on the the glomerular basement membrane cause diffuse hypocomplementemic glomerulonephritis and renal dysfunction, which typically improve with effective antimicrobial therapy. Embolic renal infracts cause flank pain and hematuria but rarely cause renal dysfunction.

24. Manifestations of specific predisposing conditions Endocarditis associated with injection drug use is limited to tricuspid valve and presents with fever but with faint or no murmur and no peripheral manifestations. Septic pulmonary emboli, which are common with tricuspid endocarditis, cause cough, pleuritic chest pain, nodular pulmonary infiltrates or occasional pyopneumothorax . Infection of aortic or mitral valves presents with typical clinical features of endocarditis, including peripheral manifestations. CIED endocarditis may be associated with obvious or cryptic generator pocket infection and results in fever, minimal murmur and pulmonary symptoms due to septic emboli. In cases arising within 60days of valve surgery(early onset) typical Late onset PVE presents with typical clinical symptoms may be obscured by comorbidity associated with recent surgery. Late onset PVE presents with typical clinical features

25. S I G NS Murmurs – Occur in less than half of the patients. New or worsened regurgitant murmur occurs. Splenomegaly Clubbing may be seen Peripheral manifestations like Osler ’s node, subungal hemorrhages, Janeway lesions, Roth’s spot.

26. Roth Spot

27. JANEWAY LESIONS

28. DI A GNOSIS

29. MODIFIED DUKE CRITERIA A highly sensitive and specific diagnostic criteria known as the Modified Duke Criteria is based on clinical, laboratory and echocardioagraphic findings commonly encountered in patients of IE. Definite Endocarditis – 2 major criterion or 1 major + 3 minor criterion or 5 minor criterion Possible IE – 1 major + 1 minor 3 minor criteria Diagnosis of IE rejected if, Alternative diagnosis established If symptoms resolve with <4 days of antimicrobial therapy If surgery or autopsy reveals no histologic evidence of IE after <4days of antimicrobial therapy

30. MAJOR CRITERIA Blood culture positive a. Typical organism (Betα hemolytic streptococcus, Streptococcus bovis , HACEK organisms, or community acquired Staphylococcus aureus or enterococcus without a primary focus) from 2 separate blood cultures Or b. Persistent positive blood culture, defined as recovery of microorganism consistent with infective endocarditis from (two positive cultures >12 hr apart or three positive cultures or a majority of ≥4 separate blood cultures , with first and last drawn at least 1hr apart Or c. S ingle positive blood culture for Coxiella burnetii or antiphase 1 IgG antibody titer >1 : 800 Evidence of endocardial involvement a. Echocardiographic findings: mobile mass attached to valve or supporting strucutres , or in path of regurgitant jets or in implanated material, in the absence of an alternative anatomic explanation Or abscess, or new partial dehiscence of prosthetic valve Or b. New valvular regurgitation

31. MINOR CRITERIA Predisposing condition: IV drug use or predisposing cardiac condition Fever ≥38° C Vascular phenomena: arterial embolism, septic pulmonary emboli, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor Microbiologic evidence: positive blood cultures not meeting major criteria or serologic evidence of active infection with an organism consistent with endocarditis

32. ECHOCARDIOGRAPHY ECHO confirms and measures vegetation, detects intracardiac complication and assesses cardiac function. TRANSTHORACIC ECHOCARDIOGRAPHY (TTE) Non invasive and specific can not detect vegetation <2mm in diameter Inadequate in emphysema and obese. Not optimal for evaluating prosthetic valve or detecting intracardiac complications.

33. TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE) Safe and detects vegetation in >90% with definite IE. Negative TEE does not exclude IE but requires repetition in 7 – 10 days. Optimal for diagnosis of PVE and intracardiac complications like myocardial abscess, valve perforation or intracardiac fistulae, and detection of vegetations in patients with CIED.

34. BLOOD CULTURE Three 2-bottle blood culture sets , separated from one an other by at least 2 h should be obtained from different venipuncture sites over 24 h. If culture remain negative two or three additional blood culture sets should be obtained. Empirical antimicrobial therapy should be with held in suspects of subacute endocarditis till cultures are obtained.

35. NON BLOOD CULTURE TESTS Serologic tests for Brucella, Bartonella, Legionella, C.burnetti, C.psittaci. PCR tests. CBC – Anemia, Leukocytosis Microscopic hematuria Elevated ESR and CRP Circulating Immune complexes Decreased complement

36. TREATMENT

37. STAPHYLOCOCCI MSSA infecting native valves – C e fazoline 2 g I V TI D for 4 – 6 wk s Or Vancomycin 15mg/kg IV BD for 4 – 6 wks Or Nafcillin , oxacillin or Flucloxacillin 2 g IV 4hrly for 4 – 6 wks MRSA infecting native valves – Vancomycin 15mg/kg IV BD or TID for 4 – 6 wks MSSA infecting prosthetic valves – Nafcillin , oxacillin or Flucloxacillin 2 g IV 4hrly for 6 – 8 wks plus plus Gentamycin 1mg/kg IM or IV TID for 2 wks Rifampicin 300mg PO TID for 6 – 8 wks MRSA infecting prosthetic valves – Vancomycin 15mg/kg IV BD for 6 – 8 wks plus Gentamyc i n 1mg/kg I M or I V TI D for 2 wk s plus Rifampicin 300mg PO TID for 6 – 8 wks

38. STREPTOCOCCI Penicillin susceptible Streptococci, S. gallolyticus Penicillin G 2 – 3 MU IV 4hrly for 4 wks or C e f t r ia x one 2 g /day as a singl e dose for 4 wk s or p l us Vancomycin 15 mg/kg BD for 4 wks Plus Gentamycin 3mg/kg IV OD as a single dose for 2 wks Relatively Penicilllin resistant Penicillin G 4 MU IV 4hrly for 4 wks or C e f t r ia x one 2 g /day as a singl e dose for 4 wk s p l us Gentamycin 3mg/kg IV OD as a single dose for 2 wks Moderately Penicillin resistant Vancomycin 15 mg/kg BD for 4 wks Gentamycin 3mg/kg IV OD as a single dose for 6 wks Penicillin G 2 – 3 MU IV 4hrly for 6 wks or Ceftriaxone 2 g/day as a single dose for 6 wks

39. ENTEROCOCCI Penicillin G 4 – 5 MU IV 4hrly + Gentamycin 1mg/kg IV TID both for 4 – 6 wks Ampicillin 2 g IV 4 hrly + Gentamycin 1mg/kg IV TID both for 4 – 6 wks Vancomycin 15 mg/kg BD + Gentamycin 1mg/kg IV TID both for 4 – 6 wks Ampicillin 2 g IV 4 hrly + Ceftriaxone 2 g IV BD both for 6 wks HACEK organisms Ceftriaxone 2 g/day IV as a single dose for 4 wks Ampicillin/ sulbactam 3 g IV 6hrly for 4 wks

40. S U R GERY Definite Indications for cardiac surgical interventions in patients with Endocarditis Moderate to severe CHF due to valve dysfunction Partially dehisced unstable prosthetic valve Persistent bacteremia despite optimal antimicrobial therapy Lack of effective microbicidal therapy S. aureus prosthetic valve endocarditis with intracardiac complication Relapse of prosthetic valve endocarditis

41. Surgery considered for improved outcome Perivalvular extension Poor responsive S.aureus endocarditis involving aortic or mitral valve Large (>10mm) hypermobile vegetation with high risk of embolism Persistent fever in culture –ve NVE Poor responsive endocarditis due to high antibiotic resistant Enterococci or gram –ve

42. OUTCOME Older age, severe comorbid conditions and diabetes, delayed diagnosis, involvement of prosthetic valves or the aortic valve, an invasive or antibiotic resistant( e.g., pseudomonas aeruginosa) pathogen, intracardiac and neurological complication and an association with health care associated with adversely affect outcome. Overall survival rates for patients with NVE caused by viridians streptococci, HACEK organisms or enterococci are 85-90%. For S.aureus NVE in patients who donot inject drugs, survival rates are 55-70%, whereas 85-90% of injection drug users survive this infection. PVE beginning within 2 months of valve replacement results in mortality rates of 40-50% where as rates are only 10-20% in later onset cases.

43. Prophylaxis Antibiotic regimens for prophylaxis of endocarditis in adults with High-Risk cardiac lesions Standard oral regimen - Amoxicillin 2g PO 1hr before procedure B. Inability to take oral medication - Ampicillin 2g IV or IM within 1hr before procedure C. Pencillin allergy - Clarithromycin or Azithromycin 500mg PO 1ht before procedure - Cephalexin 2g PO 1hr before procedure - Clindamycin 600mg PO 1hr before procedure D. Pencillin allergy, inability to take oral medication - Cefazolin or Ceftriaxone 1g IV or IM 30min before procedure - Clindamycin 600mgIV or IM 1hr before procedure

44. High-Risk Cardiac lesions for which Endocarditis Prophylaxis Is Adviced Before Dental Procedure Prosthetic heart valves Prior endocarditis Unpaired cyanotic congenital heart disease, palliative shunts or conduits Completely repaired congenital heart defects during 6 months after repair Incompletely repaired congenital heart disease with residual defects adjacent to prosthetic material Valvulopathy developing after cardiac transplantation