murtazaieppt-190820183045 (1).presentation

Infective endocarditis

1. INFECTIVE ENDOCARDITIS IN CHILDREN MURTAZA KAMAL 5 TH JAN, 2019

2. Definition Epidemiology Pathogenesis/ Pathology/ Microbiology Clinical features Diagnosis & Diagnostic criteria Treatment Preventive methods Scope of the talk…

3. Microbial infection of endocardial (endothelial) surface of heart Native/ prosthetic valves: Most frequently involved Can involve septal defects, mural endocardium, intravascular foreign devices, intracardiac patches, surgically constructed shunts, IV catheters Disease classification on basis of etiologic agent involved: Low virulence organisms (Alpha hemolytic streptococcai , enterococci, CONS): Prolonged subacute form of illness Virulent organisms (Staph aureus, strept pneumoniae, beta hemolytic streptococci): Acute clinical course Definition Gewitz M, Taubert KA. IE and prevention. In: Heart disease in infant, children andadolescents . 9 th ed. Philadelphia: Wolter Kluwer; 2016: 1441-1453

4. Less often in children than in adults 1: 1280 (0.78/1000) paediatric admissions/ year Overall frequency among children and a shift towards those with previous cardiac surgery: Increased  Improved survival among children who are at risk of IE, such as those with CHD (with/ without surgery) and hospitalised neonates CHD: Predominant underlying condition in developed world (MC: VSD, TOF, aortic valve abnormalities) Post operative IE: Long term risk after correction of complex CHD, esp those with residual defects/ surgical shunts/ prosthetic materials Epidemiology Van Hare GF, Ben- Shachar G, Liebman J, Boxerbaum B, Riemenschneider TA. Infective endocarditis in infants and children during the past 10 years: a decade of change. Am Heart J . 1984;107:1235–1240. Pasquali SK, He X, Mohamad Z, McCrindle BW, Newburger JW, Li JS, Shah SS. Trends in endocarditis hospitalizations at US children’s hospitals: impact of the 2007 American Heart Association antibiotic prophylaxisguidelines . Am Heart J 2012;143:894–899.

5. RHD: Before 1970s, 30-50% children with IE  Decreased now as prevalence of RHD decreased in developed countries 8-10% of pediatric cases: IE develops without structural heart disease: Central indwelling venous catheters  Mostly aortic or mitral valves are involved by staph aureus Neonates: 7.3% cases: Right sided heart structures involved Factors associated with IE in adults like IV drug abuse and degenerative heart diseases: Not common predisposing factor Epidemiology Cont … Baltimore RS. Infective endocarditis. In: Jenson HB, Baltimore RS,eds . Pediatric Infectious Diseases: Principles and Practice . 2nd ed. Philadelphia, PA: Saunders; 2002. Stull TL, LiPuma JJ. Endocarditis in children. In: Kaye D, ed. InfectiveEndocarditis . 2nd ed. New York, NY: Raven Press; 1992:313–327 Stockheim JA, Chadwick EG, Kessler S, Amer M, Abdel- Haq N, Dajani AS, Shulman ST. Are the Duke criteria superior to the Beth Israel criteria for the diagnosis of infective endocarditis in children? Clin Infect Dis . 1998;27:1451–1456.

6. 2 important factors: Damaged area of endothelium and Bacteremia (even transient) Structural abnormalities of heart/ great arteries+ significant pressure gradient/ turbulence  E ndothelial damage  T hrombus formation with deposition of sterile clumps of platelet and fibrin  Nonbacterial thrombus  Nidus for bacteria to adhere and form infected vegetation Bacteremia from dental procedures Bacteremia with activities such as chewing/ brushing teeth Chewing with diseased teeth or gums frequent cause of bacteremia Good dental hygiene very important in prevention Pathogenesis

7. Vegetation: Usually on low-pressure side of defect Either around defect or on opposite surface of defect where endothelial damage is established by jet effect of defect Vegetations found in PA in PDA or systemic-to-PA shunts On atrial surface of mitral valve in MR On ventricular surface of aortic valve and mitral chordae in AR On superior surface of aortic valve or at site of a jet lesion in aorta in AS Pathology

8. Streptococcus viridans , E nterococci and Staphylococcus aureus: 50%- 60% Fungi+ HACEK organisms (Haemophilus, Actinobacillus , Cardiobacterium , Eikenella , and Kingella spp.) : 17% to 30% α-Hemolytic streptococci (S. viridans ): D ental procedures/ carious teeth/ periodontal disease Enterococci: After GU/ GI surgery/ instrumentation Staphyloccocci : Postoperative endocarditis S. aureus: IV drug abusers Fungal endocarditis (poor prognosis): Sick neonates/ long-term antibiotic or steroid therapy/ after open heart surgery Fungal endocarditis: Associated with very large friable vegetations; emboli from these vegetations frequently produce serious complications Microbes: The Agent

9. S. aureus/ CONS: Indwelling vascular catheters/ prosthetic material/ prosthetic valves S. aureus/ CONS/ Candida: MCC a mong newborn infants Culture-negative endocarditis: 5-7% Patient has clinical or echo evidence of endocarditis but persistently negative blood culture results MCC: Current or recent antibiotic therapy or infection caused by a fastidious organism that grows poorly in vitro Fungal endocarditis: A rare cause of culture-negative endocarditis Diagnosis can be made only by removal of vegetation (during surgery) sometimes Microbes: The Agent …

10. Most patients have history of underlying heart defect Some patients with bicuspid aortic valve may not have been diagnosed with defect before History of a recent dental procedure/ tonsillectomy / toothache (from dental or gingival disease) Endocarditis: Rare in infancy; at this age, usually follows open heart surgery Onset usually insidious with prolonged low-grade fever and somatic complaints, fatigue, weakness, loss of appetite, pallor, arthralgia, myalgias, weight loss, and diaphoresis Clinical Features: History

11. Heart murmur: Universal (100%) Appearance of new heart murmur/ Increase in intensity of an existing murmur Fever: 80%–90%; 101° and 103°F Splenomegaly: 70% Skin manifestations: 50%; Either secondary to microembolization or as an immunologic phenomenon: Petechiae on skin/ mucous membranes/ conjunctivae Osler’s nodes: Tender, pea-sized red nodes at ends of fingers/ toes Janeway’s lesions: Small, painless, hemorrhagic areas on palms/ soles Splinter hemorrhages: Linear hemorrhagic streaks beneath nails Clinical Features: Examination

12. Clinical Features: Examination Osler Nodes Janeway lesion From AAP. Red Book Online visual library, 2006

13. Clinical Features: Examination Embolic/ immunologic phenomena in other organs: 50% Pulmonary emboli: VSD, PDA or a systemic-to-PA shunt Seizures and hemiparesis: Embolization to CNS-20% Hematuria and renal failure Roth’s spots- 5%: Oval, retinal hemorrhages with pale centers located near optic disc From AAP. Red Book Online visual library, 2006

14. Clinical Features: Examination Clubbing of fingers in absence of cyanosis rarely in chronic cases Heart failure as a complication of infection Neonate: Nonspecific and may be indistinguishable from septicemia or CHF from other causes Embolic phenomena (osteomyelitis, meningitis) common Neurologic signs and symptoms (seizures, hemiparesis, apnea )

15. Positive blood cultures: 90% in absence of previous antimicrobial therapy 50-60% pretreatment with antibiotics CBC: Anemia: 80% Leukocytosis with a shift to the left Patients with polycythemia preceding onset of IE may have normal hemoglobin ESR: Increased unless there is polycythemia. Microscopic hematuria: 30% Lab Studies

16. Main modality for detection Site of infection, extent of valvular damage and cardiac function Baseline evaluation of ventricular function and cardiac chamber dimension important for comparison later Color Doppler: Sensitive modality for detection of valvular regurgitation Role of ECHOCARDIOGRAPHY Vegetations on the aortic valve 

17. Echocardiographic findings included as major criteria in modified Duke criteria: Oscillating intracardiac mass on valves or supporting structures, in path of regurgitation jets, or on implanted material Abscesses New partial dehiscence of prosthetic valve New valvular regurgitation Role of ECHOCARDIOGRAPHY

18. TEE superior to TTE: Vegetations on prosthetic valves Detecting complications of LV outflow tract endocarditis Detecting aortic root abscess and involvement of sinus of Valsalva Absence of vegetations on echo: Does not rule out IE False-negative: Vegetations are small or have embolized and they may miss initial perivalvular abscess Repeat examinations indicated if suspicion exists without diagnosis of IE or worrisome clinical course during early treatment of IE Role of ECHOCARDIOGRAPHY

19. False-positive: An echogenic mass may represent a sterile thrombus, sterile prosthetic material, normal anatomic variation, an abnormal uninfected valve (previous scarring, severe myxomatous changes), or improper gain of echo machine Echocardiographic evidence of vegetation may persist for months or years after bacteriologic cure Role of ECHOCARDIOGRAPHY

20. Echocardiographic Features Suggesting Potential Need for Surgical Intervention Bayer et al.102 Copyright © 1998, American Heart Association, Inc.

21. Definite IE : Pathological evidence of IE: Demonstration of microorganism by culture Histology in a vegetation or from an embolic sites or an intracardiac abscess or histologic evidence of active endocarditis demonstrated in vegetation or intracardiac abscess Fulfillment of clinical criteria: 2 major criteria 1 major+ 3 minor criteria 5 minor criteria DIAGNOSIS: Modified Dukes Criteria

22. Possible IE : W hen one of the following is present: 1 major+ 1 minor criterion 3 minor criteria Rejected IE: An alternative diagnosis is established Clinical manifestations of IE have resolved within 4 days of antibiotic therapy No pathological evidence is found on direct examination of vegetation obtained from surgery or autopsy after antibiotic therapy for < 4 days Criteria for possible IE are not met DIAGNOSIS: Modified Dukes Criteria

23. 1. Blood culture positive for IE: Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans streptococci, Streptococcus bovis , HACEK group, Staphylococcus aureus ; or community-acquired enterococci in absence of a primary focus or Microorganisms consistent with IE from persistently positive blood cultures defined as: at least 2 positive cultures of blood samples drawn >12 h apart or all of 3 or a majority of 4 or more separate cultures of blood (with first and last sample drawn at least 1 h apart) Single positive blood culture for Coxiella burnetii or anti–phase 1 IgG antibody titer >1:800 Modified Dukes: Major Criteria

24. 2. Evidence of endocardial involvement Echocardiogram positive for IE (TEE recommended for patients with prosthetic valves, rated at least “possible IE” by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients) defined as follows: Oscillating intracardiac mass on valve or supporting structures, in path of regurgitant jets, or on implanted material in absence of an alternative anatomic explanation Abscess New partial dehiscence of prosthetic valve New valvular regurgitation (worsening or changing or preexisting murmur not sufficient) Modified Dukes: Major Criteria

25. Predisposition, predisposing heart condition, or IDU Fever, temperature >38°C Vascular phenomena: Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages and Janeway’s lesions Immunologic phenomena: Glomerulonephritis, Osler’s nodes, Roth’s spots and rheumatoid factor Microbiologic evidence: Positive blood culture but does not meet a major criterion or serologic evidence of active infection with organism consistent with IE Modified Dukes: Minor Criteria

26. Blood cultures: Indicated for all patients with fever of unexplained origin and a pathologic heart murmur, a history of heart disease or previous endocarditis Usually 3 blood cultures are drawn by separate venipunctures over 24 hours unless patient is very ill 90% of cases, causative agent is recovered from 1 st 2 cultures If no growth by 2 nd day of incubation, 2 more may be obtained No value in obtaining >5 blood cultures over 2 days unless patient received prior antibiotic therapy Not necessary to obtain cultures at any particular phase of fever cycle Adequate volume: 1-3 mL infants; 5-7 mL older children Aerobic incubation alone sufficient Management

27. Recommended that consultation from local infectious disease specialist be obtained when IE suspected/confirmed: Antibiotics of choice continually changing, and there may be special situation pertaining to local area Initial empirical therapy : Usual initial regimen: Antistaphylococcal semisynthetic penicillin ( nafcillin,oxacillin or methicillin)+ aminoglycoside (gentamicin) Covers against S. viridans , S. aureus, and gram-negative organisms Vancomycin: Methicillin-resistant S. aureus suspected Penicillin-allergic patients Management

28. Depends on organism isolated+ results of antibiotic sensitivity tes t Streptococcal IE: Native cardiac valve IE caused by highly sensitive S. viridans : IV penicillin (or ceftriaxone OD) X 4 weeks Alternatively penicillin, ampicillin or ceftriaxone+ gentamicin for 2 weeks IE caused by penicillin-resistant streptococci: 4 weeks of penicillin, ampicillin or ceftriaxone+ gentamicin for 2 weeks Final antibiotic selection

29. Staphylococcal endocarditis: Drug of choice native valve IE by methicillin-susceptible staphylococci: Semisynthetic β-lactamase–resistant penicillins (nafcillin, oxacillin or methicillin) X minimum of 6 weeks (± gentamicin X 3–5 days) Methicillin-resistant native valve IE: Vancomycin X 6 weeks (± gentamicin X 3–5 days) Enterococcus: IV penicillin/ ampicillin+ gentamicin X 4 to 6 weeks Allergic to penicillin: Vancomycin +gentamicin x 6 weeks HACEK organisms: Ceftriaxone/ another 3 rd generation cephalosporin alone or ampicillin+ gentamicin x 4 weeks Final antibiotic selection

30. IE by other gram-negative bacteria ( E coli , Pseudomonas aeruginosa , or Serratia marcescens ): P iperacillin / ceftazidime together+ gentamicin X 6 weeks Amphotericin B: Most effective agent for most fungal infections Culture-negative endocarditis: Treatment directed against staphylococci, streptococci and HACEK organisms using ceftriaxone+ gentamicin When staphylococcal IE suspected, nafcillin should be added to the above therapy Final antibiotic selection

31. Should be treated for 6 weeks based on organism isolated and results of sensitivity test Operative intervention may be necessary before antibiotic therapy is completed if clinical situation warrants: Progressive CHF Significant malfunction of prosthetic valves Persistently positive blood cultures after 2 weeks of therapy Bacteriologic relapse after an appropriate course of therapy Prosthetic valve Endocarditis

32. Overall recovery rate: 80%- 85% 90% or better: S. viridans and enterococci 50%: Staphylococcus organisms Fungal endocarditis: Very poor outcome Prognosis

33. Prevention Emphasis should be on maintaining good oral hygiene and eradicating dental disease to decrease frequency of bacteremia from routine daily activities Recommended for tonsillectomy and adenoidectomy only in high-risk patients Prophylaxis no longer recommended: For routine bronchoscopy For GI or genitourinary procedures, such as diagnostic esophagogastroduodenoscopy or colonoscopy

34. Patients with prosthetic cardiac valve/ material used for cardiac valve repair Patients with previous IE Patients with CHD: Unrepaired cyanotic CHD, including palliative shunts/ conduits Completely repaired CHD with prosthetic material/ device, whether placed by surgery or catheter intervention, during 1 st 6 months after procedure Repaired CHD with residual defects at site or adjacent to site of a prosthetic patch/ device (which inhibits endothelialization ) Cardiac transplantation recipients with valve regurgitation caused by a structurally abnormal valve Cardiac conditions for which prophylaxis With dental procedures is recommended

35. Dental procedures: Involving manipulation of gingival tissue of periapical region or perforation of oral mucosa Respiratory tract procedures: Procedures that involve incision/ biopsy of respiratory mucosa Not recommended for bronchoscopy GI or GU procedures: No prophylaxis for diagnostic esophagogastroduodenoscopy/ colonoscopy Reasonable in patients with infected GI/GU tract Skin, skin structure or musculoskeletal tissue: Surgical procedures that involve infected skin, skin structure, or musculoskeletal tissue Procedures for which IE Prophylaxis is recommended

36. Prophylactic regimens for Dental procedures Park. Pediatric cardiology for practitioners; 6 th edition

37. Special Considerations Patients already receiving antibiotics: Rheumatic fever prophylaxis: Use other antibiotics, such as clindamycin, azithromycin or clarithromycin Delay a procedure until 10 days after completion of antibiotic Patients who undergo cardiac surgery: Careful preoperative dental evaluation so that required dental treatment may be completed whenever possible before surgery Prophylaxis at time of surgery: Primarily against staphylococci Prophylaxis should be initiated immediately before surgery, repeated during prolonged procedures to maintain serum concentrations intraoperatively, and continued for no more than 48 hours postoperatively

38. IE in children is not uncommon Common in children with CHD Neonates: Poor outcome Blood culture + ECHO has important role in diagnosis Treatment adherence necessary Prognosis not bad if treated properly Knowledge of conditions requiring prophylaxis and drugs for it necessary Take Home Message

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