1. MEDICAL MANAGEMENT OF INFECTIVE ENDOCARDITIS IN CHILDREN
Ndubueze Ezemba
Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town
Hannes Meyer Symposium 13 April 2008

2. OUTLINE
Introduction Epidemiology Classification Aetiopathogenesis Management Investigation Treatment Outcome Conclusion

3. INTRODUCTION
DEFINITION Infective endocarditis may be defined as conditions in which structures of the heart, most frequently the valves, harbour an infective process that leads to valvar dysfunction, localized or generalized sepsis, or sites for embolism (1). It includes acute, subacute, and chronic processes; infection of bacterial, viral, rickettsial, or fungal aetiology. It may be native valve endocarditis (NVE) or prosthetic endocarditis. It is the most feared complications of structural heart lesions.

4. EPIDEMIOLOGY
The incidence of infective endocarditis(IE) is difficult to estimate because true population characteristics, including both cases and total population at risk, are difficult to obtain. There is an increasing incidence of IE in children. One paediatric cardiology unit puts the incidence as high as 32/1000 hospital admissions in children < 16 years of age (2).

5. CLASSIFICATION
MODE OF PRESENTATION Acute Subacute Chronic MICROBIOLOGICAL ORGANISM Bacterial Viral Rickettsial Fungal Culture negative

6. CLASSIFICATION
STATUS OF THE HEART Native Endocarditis Replacement Device Endocarditis i. valve prostheses ii. Patch iii. Shunts iv. Homografts v. pacemaker

7. AETIOPATHOGENESIS: Aetiology
Microbiology of Infective Endocarditis
Gram – Positive Cocci
a. Streptococci
Viridans streptococci remain the major cause of endocarditis in children.
b. Staphylococci
Streptococci and staphylococci account for – 90% of culture positive IE (3,4).

8. AETIOPATHOGENESIS
Staphylococci cause at least 30 – 40% of cases of IE, and 80 – 90% of these are due to coagulase-positive S. aureus. This species is the causative agent in most cases of acute IE. The organism may attack normal heart valves in approximately one-third of the patients. The course is frequently fulminant when it involves the mitral or aortic valve, with widespread metastatic infection, and result in death in approximately 25 – 30 % of the patients.

9. AETIOPATHOGENESIS
Myocardial abscesses (with conduction disturbances), purulent pericarditis, and peripheral foci of suppuration are more common in staphylococcus IE than in other forms of infective endocarditis. The rare entity of neonatal endocarditis is also often caused by S. aureus; survival is unusual. THUS STAPHYLOCOCCUS AUREUS ENDOCARDITIS FROM THE START MAY BE CONSIDERED A SURGICAL DISEASE.

10. AETIOPATHOGENESIS Gram-Negative Bacilli
i. Enterobacteriaceae, Salmonella species are important cause of IE. These organisms have an affinity for abnormal cardiac valves, usually left sided heart valves.
ii. Pseudomonas endocarditis is rare in children being commoner in replacement device endocarditis.
HACEK and other unusual Gram-Negative Bacteria
The HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) bacteria are fastidious and originally required 2 to 3 weks for primary isolation.
They produce large large friable vegetations, frequent emboli, and the development of CCF.

11. AETIOPATHOGENESIS
D. Gram-Positive Bacilli i. Corynebacteria(diphtheroids) ii. Listeria monocytogenes E. Anaerobic Bacteria i. Bacteroides fragilis These are all rare causes of infective endocarditis in children as in adults.

12. AETIOPATHOGENESIS
F. Fungal Most patients who have fungal endocarditis have undergone reconstructive cardiovascular surgery, or may have received prolonged intravenous antibiotic therapy. The overall cure rate for fungal IE is poor(14.5%) in part due to; a. poor penetration of antifungal agents into the vegetation b. low toxic-therapeutic ratio of the available antifungal agents c. the usual lack of fungicidal activity with these agents A cure is usually impossible without surgical intervention. G. Very Unusual Microorganisms i. Coxiella burnetii (Q fever) ii. Chlamydia

13. AETIOPATHOGENESIS “CULTURE –NEGATIVE” ENDOCARDITIS
The prevalence of “culture negative” endocarditis in a recent study in Western Cape is put at >50% 5.
Factors responsible for this include;
i. prior administration of antibiotics
ii. cultures taken towards the end of a chronic course
iii. mural endocarditis as in VSDs
iv. Slow growth of fastidious organisms such as anaerobes
v. fungal endocarditis
vi. endocarditis due to obligate intracellular parasites, eg rickettsia
When strict diagnostic criteria are applied blood cultures are negative in only about 5% of patients with IE (6).

14. PATHOGENESIS
Predisposing Factors to IE Rheumatic heart disease Congenital heart diseases Previous cardiac interventional procedures With a few exceptions, the endothelial lining of the heart and valves is generally resistant to infection. Development of endocarditis involves a complex interaction between; i. The host immune system ii. The haemostatic mechanism iii. Cardiac anatomic chambers iv. Surface properties of the microorganism v. Enzymes and toxins produced by microorganism vi. Peripheral events that have caused the bacteraemia

15. PATHOGENESIS
Endothelial damage is the inciting event Platelet – fibrin deposition provides a milieu for bacterial colonization Bacteria must be present to colonize the vegetation Adherence of the microoganism to the vegetation or the intact valve endothelium mediated by adhesion molecules(MSCRAMMS) Multiplication and internalization within the host cells Invasion of the endothelium causing cell death and disruption of the endothelial surface further promotes platelet – fibrin deposits.

16. Fig:1 steps in the development of endocarditis lesion

17. Fig. 2 Sites of high-velocity jets where endocarditis vegetations occur The areas of vegetation formation are similar to those where blood flow injury is likely to occur These are; a. atrial side of AV valves b. ventricular side of semilunar valves c. jet lesions(McCallum patches)

18. PATHOPHYSIOLOGY
Endocarditis vegetation on native valve interferes with valve motion resulting in regurgitation Vegetation growth results in leaflet perforation and may cause chordal rupture Infection extension into surrounding structures such as sinotubular juction, annulus, myocardium, conduction tissue

19. PATHOPHYSIOLOGY
Cavitation in the aortic wall leads to periaortic abscess Abscess may occasionally erode into pericardium or another cardiac chamber. Large vegetations on prosthetic valves can lead to both regurgitation and obstruction. Vegetations on patches leads to dehiscence Vegetation may embolize

20. Complications of IE Congestive heart failure 50–60%
Embolization 20–25%
CVA 15%
Other emboli
Limb 2–3%
Mesenteric 2%
Splenic 2–3%

21. Complications of IE Glomerulonephritis 15–25% Anular abscess 10–15%
Myocotic aneurysm –15%
Conduction system involvement –10%
CNS abscess –4%
Other less common complications 1–2%
Pericarditis
Myocarditis
Myocardial infarction
Intracardiac fistula
Metastatic abscess

22. MANAGEMENT DIAGNOSTIC MEASURES Clinical features
Blood culture, FBC, CUE, LFT
- blood culture results provide much useful information that has immediate importance for management decisions.
Provides the identity of the presumed organism
May point to the source of bacteraemia which is useful in preventive measures
Provides initial guidance with regard to antibiotic therapy
It gives important prognostic information about the likelihood of surgical intervention.

23. DIAGNOSTIC MEASURES
Optimal procedures must be used in obtaining samples for blood culture (6):
a. Optimal antiseptic skin preparation
b. Optimal timing of blood culture
c. Optimal number of blood cultures
d. The volume must be optimal;
i. 1-2ml/culture for neonates
2-3ml/culture for infants aged 1 month to 2 years
3-5ml for older children
10-20ml for adolescents
e. Length of incubation must be adequate

24. DIAGNOSTIC MEASURES Vegetation Abscess Aneurysm Fistulae
Echo: Characteristics of IE
Vegetation
Abscess
Aneurysm
Fistulae
Leaflet perforation
Valvular dehiscence

25. ECHO

26. Fistula formation during IE: infected sinus of Valsalva aneurysm that has ruptured into RVOT and RA

27. DIAGNOSTIC MEASURES
ECG CXR OTHERS CT SEROLOGY

28. MAKING A DIAGNOSIS: THE MODIFIED DUKE’S CRITERIA
The modified Duke criteria* 1. Major criteria a. Microbiologic Typical microorganisms isolated from two separate blood cultures, or microorganism isolated from persistently positive blood cultures, or single positive blood culture for Coxiella burnetii (or phase I IgG antibody titer to C. burnetii 1:800) b. Evidence of endocardial involvement New valvular regurgitation or positive echocardiogram (intracardiac mass, or periannular abscess, or new dehiscence of prosthetic valve)

29. MODIFIED DUKE’S CRITERIA
2. Minor criteria
a. Predisposition to infective endocarditis
i. Previous infective endocarditis
ii. Injection drug use
iii. Prosthetic heart valve
iv. Mitral valve prolapse
v. Cyanotic congential heart disease
vi. Other cardiac lesions creating turbulent flow within the intracardiac chambers
b. Fever
c. Vascular phenomena (eg, embolic event)
d. Immunologic phenomena (eg, presence of serologic markers, glomerulonephritis,
Osler’s nodes, or Roth spots)
e. Microbiologic findings not meeting major criteria
*Definite endocarditis requires 2 major criteria or 1 major and 3 minor criteria or 5 minor.
Possible endocarditis requires 1 major and 1 minor or 3 minor criteria

30. TREATMENT Principles for medical treatment of IE (7)
A. Bactericidal therapy must be used
ideally culture-directed
Adequate dosing of the appropriate antibiotic (monitor the MIC).
Prolonged course of therapy.
Other adjuctive measures
diurectics
ACE inhibitors
inotropes
ventilatory support.
E. Evaluation of clinical response and early surgical consultation

31. TREATMENT OUTCOME/PREDICTORS OF MORTALITY (8) Vegetation size ≥20mm
Age<1 year
Presence of heart failure
S. aureus as causative organism

32. CONCLUSION
Infective endocarditis remains a common disease in children. Streptococci and Staphylococci account for over 80% of cases. Staphylococci infective endocarditis is usually a fulminant disease. Best medical treatment hinges on culture directed antimicrobial with early surgical consultation.

33. References
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34. References
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