INFECTIVE ENDOCARDITISDr.Anup John ThomasAssistant ProfessorDepartment of Pediatrics,MGMC&RI

History• 1885 – well defined by William Osler• 1944 – penicillin discovered• 1960 – surgery in IE• 1973 – ECHO for identifying vegetation• 1981 – Von Reyn criteria• 1994 – Dukes criteria

Definition• Infectious Endocarditis (IE): an infection of the heart’s

endocardial surface

Background• Relatively rare in children• Pre-antibiotic era: mortality was nearly 100%• Mortality approaches 15-25%

Classification• 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

Pathophysiology

1. Turbulent blood flow disrupts the endocardium making it “sticky”

2. Bacteremia delivers the organisms to the endocardial surface

3. Adherence of the organisms to the endocardial surface

4. Eventual invasion of the valvular leaflets

Epidemiology• Incidence difficult to ascertain and varies according to

location• Much more common in males than in females• Increasing incidence beginning in the ‘80s

• Increasing number of surgical patients• Increasing number of complex congenital heart disease• Increased use of prosthetic materials• NICUs and PICUs

Difficult to eradicate: why?

• Less awareness of risks & preventive measures• Delay in diagnosis• Special risk groups

Risk Factors• The vast majority (75-90%) of cases after the neonatal

period are associated with an underlying congenital abnormality

• Aortic valve• VSD• Tetralogy of Fallot

• Risk of post-op infection in children with IE is 50%• Artificial heart valves and pacemakers • Acquired heart defects

• Calcific aortic stenosis• Mitral valve prolapse with regurgitation

• Intravascular catheters• Intravenous drug abuse

Microbiology• S. Viridans

• Most common causative organism• Gram negative bacilli

• Neonates and immunocompromised patients• Prosthetic valves

• Within first year of surgery: Coag-negative staph• Staph.epidermidis • After first year: similar to native valve endocarditis

• HACEK organisms• Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella• Frequently affect damaged valves and can cause emboli

• Candida • 6 -10 % culture negative.

Symptoms• Acute

• High grade fever and chills• Breathlessness• Arthralgia/ myalgia• Abdominal pain• Pleuritic chest pain• Back pain

• Subacute• Low grade fever• Anorexia• Weight loss• Fatigue• Arthralgia/ myalgia• Abdominal pain

The onset of symptoms is usually ~2 weeks or less from the initiating bacteremia

Signs• Fever • Heart murmur• Nonspecific signs – petechiae, subungual or “splinter”

hemorrhages, clubbing, splenomegaly, neurologic changes

• More specific signs - Osler’s Nodes, Janeway lesions, and Roth Spots

Petechiae

Subconjunctival Hemorrhage

1.Nonspecific2.Often located on extremities

or mucous membranes

Splinter Hemorrhages

1. Nonspecific2. Nonblanching3. Linear reddish-brown lesions found under the nail bed4. Usually do NOT extend the entire length of the nail

Osler’s Nodes

1. More specific2. Painful and erythematous nodules3. More common in subacute IE

Janeway Lesions

1. More specific2. Erythematous, blanching macules 3. Nonpainful

Roth’s Spots

Diagnosis• Traditionally based upon “positive blood cultures in the

presence of a new or changing heart murmur”, or persistent fever in the presence of heart disease.

• Shortcomings include culture-negative endocarditis, lack of typical echocardiographic findings, etc.

The Essential Blood Test• Blood Cultures

• Minimum of three blood cultures• Three separate venipuncture sites• 0.5-5mL in children

• 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

Additional Labs• CBC:normochromic normocytic anemia and/or

leukocytosis• ESR and CRP elevated• Complement levels ↓ (C3, C4, CH50)• RF• Urinalysis: Microscopic hematuria• Baseline chemistries and coagulation profile

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

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

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”

Duke Criteria• Based on pathological and clinical criteria.• Utilizes microbiological data, evidence of endocardial involvement, and other phenomenon associated with infective endocarditis to estimate the probability of infective endocarditis in a given patient.

• Has been shown to be valid and reproducible in children

Modified Duke Criteria• Definite IE

• Pathological• Microorganism (via culture or

histology) in a valvular vegetation, embolized vegetation, or intracardiac abscess

• Histologic evidence of vegetation or intracardiac abscess

• Clinical• 2 major• 1 major and 3 minor• 5 minor

• Possible IE

• At least 1 major and 1 minor,• 3 minor

• Rejected IE• Firm alternative diagnosis, or• Resolution of manifestations of

endocarditis with antibiotic therapy of 4 days or less, or

• No pathological evidence of endocarditis at surgery or autopsy with antibiotic therapy of 4 days or less

Duke criteria: Major criteria• Positive blood culture

• Typical microorganism consistent with IE, from two separate blood cultures• S. viridans, S. bovis, HACEK• community-acquired S. aureus or enterococci (no primary focus)

• Persistently positive cultures• at least two positive cultures, drawn 12 hours apart• all of three, or a majority of four or more cultures (with first and last

sample drawn at least one hour apart• Evidence of endocardial involvement

• Positive echocardiogram• oscillating intracardiac mass on valve or supporting structures, or• myocardial abscess, or• new partial dehiscence of prosthetic valve

• New valvular regurgitation

The echocardiogram in IE

Duke criteria: Minor criteria• Predisposition

• Predisposing heart condition or IV drug abuser

• Fever• > 38.0º C

• Vascular phenomena• arterial emboli, septic pulmonary

infarct, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, Janeway’s lesion

• Immunologic phenomena• glomerulonephritis, Osler’s nodes,

Roth’s spots, rheumatoid factors • Microbiologic evidence

• positive blood culture but does not meet major criteria as noted

• Echocardiographic evidence• consistent with IE but does not meet

major criteria as noted

Treatment• Parenteral antibiotics

• High serum concentrations to penetrate vegetation• Prolonged treatment to kill dormant bacteria clustered in vegetation

• Surgery• Intracardiac complications

• Surveillance blood cultures

Treatment• Parenteral antibiotics• strep Viridans : 4wks

• penicillin 20Lakh u/kg/d• ceftriaxone 100mg/kg/d• vancomycin 30/mg/kg/d • prosthetic valve; 6wks

• Staph aureus: • cloxacillin+ gentamicin [6wks]• vancomycin [clox resistant ]• prosthetic valve: add rifampicin & GM > 6wks

Treatment• Parenteral antibiotics• Enterococcus: ampicillin + GM /streptomycin• vancomycin / linezolid• HACEK: ceftriaxone / ampicillin+GM / ciprofloxacin• Candida : amphotericin+ 5 flurocytosine• Recombinant tissue plasminogen activation

Surgical Treatment of Intra-Cardiac Complications

• NYHA Class III/IV CHF due to valve dysfunction

• Unstable prosthetic valve• Uncontrolled infection

Sequelae• Neurologic manifestations, 20%

• Cerebral emboli, mycotic aneurysms, cerebritis, brain abscess, hemorrhage, etc.

• Peripheral embolization• Ischemia, infarction, mycotic aneurysms, etc.

• Pulmonary infarction• Renal insufficiency• Congestive heart failure

Embolic Complications• Occur in up to 40% of patients with IE• Predictors of embolization

• Size of vegetation• Left-sided vegetation• Fungal pathogens, S. aureus, and Strep. Bovis

• Incidence decreases significantly after initiation of effective antibiotics

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)

Poor Prognostic Factors• Female• S. aureus• Vegetation size• Aortic valve • Prosthetic valve• Older age

• Low serum albumin • Heart failure• Paravalvular abscess• Embolic events

Prevention

• Prophylactic regimen targeted against likely organism• Strep. viridans – oral, respiratory, esophageal • Enterococcus – genitourinary, gastrointestinal• S. aureus – infected skin, mucosal surfaces

Endocarditis prophylaxis recommended

• High-risk• Prosthetic cardiac valves• Previous bacterial endocarditis• Complex cyanotic heart disease• Surgically constructed systemic-pulmonary shunts or conduits

• Moderate-risk• Most other congenital heart disease• Acquired valvar dysfunction• Hypertrophic cardiomyopathy• Mitral valve prolapse WITH regurgitation and/or thickened leaflets

Dental procedures and IE prophylaxis: Recommended• Dental extractions• Periodontal procedures• Dental implants and reimplantation of avulsed teeth• Endodontic procedures• Subgingival placement of antibiotic fibers and strips• Initial placement of orthodontic bands (not brackets)• intraligamentary local anesthetic injections• Prophylactic cleaning

Other procedures and IE prophylaxis: Recommended• Respiratory

• T&A• Surgical procedures involving respiratory mucosa• Rigid bronchoscopy

• Gastrointestinal• Sclerotherapy• Esophageal stricture dilation• ERCP with biliary obstruction• Surgery involving biliary tract or intestinal mucosa

• Genitourinary tract• Prostatic surgery, cystoscopy• Urethral dilation

Prophylaxis

• Dental & oral & URT procedures; oral amox 50mg/kg 1hr beforeIM/IV ampicillin 50mg/kg 30mt beforeoral cephalexin / azithromycinIV cefazolin

GIT / GUT surgery

• Moderate risk: Oral amox / IV ampicillin

• High risk:IV ampicillin+ GM 30mt before & oral amox 6h

laterVancomycin + GM 30 mt before

Thank You