INFECTIVE ENDOCARDITIS IN CHILDREN

PRESIDENTIAL ACTION PLAN 2018
Ref:
INFECTIVE ENDOCARDITIS IN CHILDREN
MURTAZA KAMAL
5TH JAN, 2019

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

Ref:
 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. 9th ed. Philadelphia:
Wolter Kluwer; 2016: 1441-1453

Ref:
 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, RiemenschneiderTA. 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.

Ref:
 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, DajaniAS, 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.

Ref:
 2 important factors:
 Damaged area of endothelium and
 Bacteremia (even transient)
 Structural abnormalities of heart/ great arteries+ significant
pressure gradient/ turbulence Endothelial damage Thrombus
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

Ref:
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

Ref:
 Streptococcus viridans, Enterococci and Staphylococcus
aureus: 50%- 60%
 Fungi+ HACEK organisms (Haemophilus, Actinobacillus,
Cardiobacterium, Eikenella, and Kingella spp.): 17% to 30%
 α-Hemolytic streptococci (S. viridans): Dental 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

Ref:
 S. aureus/ CONS: Indwelling vascular catheters/ prosthetic material/
prosthetic valves
 S. aureus/ CONS/ Candida: MCC among 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…

Ref:
 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

Ref:
 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

CLINICAL FEATURES: EXAMINATION
Osler Nodes Janeway lesion
From AAP. Red Book Online visual library, 2006

Ref:
 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

Ref:
 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)

Ref:
 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

Ref:
 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

Ref:
 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

Ref:
 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

Ref:
 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

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

Ref:
 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

Ref:
 Possible IE: When 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

Ref:
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

Ref:
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

Ref:
 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

Ref:
 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 1st 2 cultures
 If no growth by 2nd 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

Ref:
 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

Ref:
 Depends on organism isolated+ results of antibiotic sensitivity test
 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

Ref:
 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 3rd generation cephalosporin alone or
ampicillin+ gentamicin x 4 weeks

Ref:
 IE by other gram-negative bacteria (E coli, Pseudomonas
aeruginosa, or Serratia marcescens):
 Piperacillin/ 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

Ref:
 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

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

Ref:
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

Ref:
 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 1st
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

Ref:
 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

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

Ref:
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

Ref:
 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

Ref:
THANK YOU

INFECTIVE ENDOCARDITIS IN CHILDREN

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