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Endocarditis
Leigh Bragg, MD,*
Educational Gaps
Ana Alvarez, MD*
1. Because of its associated mortality rate (20%-25%), clinicians must recognize that
infective endocarditis can affect children without a history of cardiac abnormality. (1)
Author Disclosure 2. Pediatricians should be aware of the recently revised American Heart Association
Drs Bragg and Alvarez recommendations for antimicrobial prophylaxis of infective endocarditis in children. (2)
have disclosed no
financial relationships
Objectives After completing this article, readers should be able to:
relevant to this article.
This commentary does 1. List the risk factors for infective endocarditis (IE).
not contain 2. Recognize the signs, symptoms, and Duke criteria that aid in the diagnosis of IE.
a discussion of an 3. Determine the appropriate laboratory tests and imaging necessary to aid in diagnosing IE.
unapproved/ 4. Discuss the medical and surgical management used in the treatment of IE.
investigative use of 5. Identify the population and procedures in which prophylactic antibiotics are used to
a commercial product/ prevent IE.
device.
Case 1
A previously healthy 3-year-old boy presents with 5 days of fever, chills, malaise, and vomit-
ing. On examination, his temperature is 102.4F (39.1C). He is lethargic and has pete-
chiae on the buccal mucosa and extremities. He is admitted to the hospital for evaluation
and treatment of sepsis of unknown origin. Three blood cultures that were performed on
separate occasions reveal gram-positive cocci on Gram stain. Echocardiography (ECHO) is
performed because of concern for endocarditis.
Case 2
A 14-year-old girl with congenital heart disease (CHD) underwent an aortic valve replace-
ment with a bioprosthetic valve 3 years previously. She presents today at the emergency
department with shortness of breath and peripheral edema. On examination, she is afebrile
but has a new harsh diastolic murmur and hepatomegaly. ECHO reveals a 1.5-cm vegetation
on the aortic valve. She is admitted to the intensive care unit and given broad-spectrum
antibiotics. After 24 hours, she continues to clinically deteriorate and is taken to the op-
erating room for valve replacement. Three blood cultures performed before the initiation
of antibiotic therapy yield Streptococcus mitis.
Epidemiology
Abbreviations Pediatric patients are rarely diagnosed as having infective en-
AACEK: Aggregatibacter parainuenzae, Aggregatibacter docarditis (IE); however, IE is a signicant cause of morbid-
actinomycetemcomitans, Cardiobacterium ity and mortality in children. Most often IE is a complication
hominis, Eikenella corrodens, and Kingella species of CHD, but it can occur in children who do not have a car-
AHA: American Heart Association diac abnormality. The epidemiology of endocarditis has
CHD: congenital heart disease changed throughout the years as the prevalence of rheu-
CVC: central venous catheter matic heart disease has decreased and the survival of patients
IE: infective endocarditis with CHD and the use of indwelling central venous cathe-
ECHO: echocardiography ters (CVCs) have increased. Because of these changes, the
actual incidence of IE is hard to determine.
*Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Florida College of Medicine Jacksonville,
Jacksonville, FL.
Traditionally, data from several pediatric studies indi- secondary to CHD or from indwelling CVCs. Once the en-
cate that most pediatric patients with IE had CHD; how- dothelium is damaged, platelets and brin are deposited on
ever, one study found that 56% of pediatric IE patients its surface, forming a nonbacterial thrombotic endocarditis.
did not have preexisting heart conditions. (3) The in- The thrombus is then colonized by microorganisms invad-
crease of IE in children without cardiac abnormalities ing the bloodstream, creating an infected vegetation.
in this study was thought to be secondary to the use of Bacterial pathogens (streptococci and staphylococci
indwelling CVCs and the diverse population studied, spp) have unique surface components that facilitate at-
which included children from numerous centers across tachment to the surface of damaged endothelium. Once
the United States. Even though patient characteristics attached to the vegetation, the bacteria are further cov-
with IE have evolved, the pathogens associated with IE ered with brin and platelets, thus evading host defense
in pediatric patients have not changed. mechanisms and allowing rapid multiplication. Foreign
valves, pacemaker wires, and CVCs can also develop bio-
lms on the surface where pathogens can adhere and
Etiology replicate.
The most common organisms responsible for IE in pedi-
atric patients with or without CHD are viridans strepto-
cocci and Staphylococcus aureus. Viridans streptococci are Clinical Manifestations
a large heterogeneous group of gram-positive cocci that The clinical presentation of pediatric IE can be classied as
are part of the oral microora, and they are commonly either a subacute or acute process. Subacute presentation
associated with transient bacteremia occurring with den- typically manifests as nonspecic symptoms for several
tal procedures and even with daily oral hygiene. There are weeks, whereas acute IE generally presents as a rapidly pro-
more than 15 different species in the group (eg, Strepto- gressive serious illness. Patients can have mixed features,
coccus sanguis, S mitis, Streptococcus oralis, and Streptococ- and the most common signs and symptoms are listed in
cus anginosis), and they have been associated with Table 1. Children rarely have the classic signs of IE that
infection of abnormal valves (CHD or previous acute develop late in disease, such as Roth spots (small retinal
rheumatic fever) and with late postoperative endocarditis, hemorrhages), Janeway lesions (small, painless, hemor-
which occurs more than 6 months after cardiac valve sur- rhagic lesions on the palms and soles), Osler nodes (small,
gery. S aureus can cause IE in structurally normal and tender, intradermal nodules on the ngers and toes), and
abnormal hearts. Although gram-positive bacteria are splinter hemorrhages (linear streaks beneath the nail beds).
the most common pathogens implicated in IE, gram- Pediatricians should be familiar with the manifestations of
negative bacteria, better known as AACEK (Aggregatibacter IE in children so that a prompt diagnosis can be attained.
parainuenzae, Aggregatibacter actinomycetemcomitans,
Cardiobacterium hominis, Eikenella corrodens, and King-
ella species) organisms, can cause IE in children. Fungi, most
commonly Candida and Aspergillus, can also be respon-
Common Manifestations of
Table 1.
sible for IE, especially in hospitalized patients who have Pediatric Infective Endocarditisa
prosthetic valves or indwelling CVCs. Culture-negative IE
Manifestation Frequency, %
has been described and occurs in approximately 5% to 10%
of children, less than that seen in adults. (4) Symptoms
Fever 75100
Malaise 5075
Pathogenesis Anorexia 2550
Transient bacteremia is thought to originate from a dis- Heart failure 2550
Arthralgia 1750
ruption in host mucosal surfaces (oropharynx, gastroin-
Signs
testinal tract, and genitourinary tract) heavily colonized Splenomegaly 5075
with microora. Dental procedures and daily activities, Embolic phenomenon 2550
such as chewing foods and brushing teeth, have been im- Murmur (new or changing) 2150
plicated as sources of transient bacteremia. Petechiae 2150
When bacteremia is present, IE can result from the com- a
Adapted from Levasseur S, Saiman L. Endocarditis and other
plex interaction among microorganisms, platelets, and - intravascular infections. In: Principles and Practice of Pediatric
Infectious Diseases, 4th ed, Long SS, Pickering LK, Prober CG, eds.,
brin at the site of damaged cardiac endothelium. The 256-265. Copyright Saunders Elsevier (2012).
endothelium can be damaged from turbulent blood ow
Diagnosis Imaging
IE is a complex syndrome that requires the presence of ECHO is the primary imaging modality used in the diag-
multiple ndings to establish the diagnosis. Identication nosis and treatment of IE. ECHO should be performed
when there is a high index of suspicion for IE, especially of offending agents which typically requires prolonged
in patients with CHD or indwelling CVCs who have per- courses of antibiotics.
sistent bacteremia. It allows visualization of the abnormal-
ities listed in the Duke criteria: vegetations, abscesses, or Antibiotic Therapy
prosthetic valve dehiscence (Figure). It also allows moni- To prevent further endocardial damage and complications,
toring of abnormalities and cardiac function. In contrast to it is imperative that antibiotic therapy be initiated promptly
adults, transthoracic ECHO is highly sensitive in pediatric in patients with suspected IE. Antibiotic regimens for IE
patients and is most commonly used. Transesophageal are based on the patients age, clinical presentation, cardiac
ECHO is more invasive but can be used to evaluate pa- status, and organisms most commonly isolated in infec-
tients with complex heart disease or when there is poor vi- tions. Intravenous bactericidal antibiotics are necessary
sualization with transthoracic ECHO. Although ECHO is for the treatment of IE, and high serum levels are required
a useful diagnostic tool for IE, vegetations are not always to eliminate bacterial growth at the site of infection.
visualized early in the disease, and their absence does not Before identication of a pathogen and after appropri-
rule out IE. If there is a continued suspicion for IE, ate volume blood cultures are obtained, empiric vanco-
ECHO should be performed again in 7 to 10 days. mycin and gentamicin therapy is recommended because
In patients who have denite IE, ECHO is essential to this regimen provides coverage against the most common
monitor heart function and the presence and size of veg- pathogens of IE, S aureus and viridans streptococci. If a
etations during therapy and to determine the risk of em- specic pathogen is identied in culture, the antibiotic
bolization. Other imaging modalities have been introduced regimen can be tailored based on susceptibility proles.
but are not yet widely used for diagnosing IE in pediatrics. Typically, 4 to 6 weeks of therapy is recommended in
These modalities include cardiac computed tomography uncomplicated cases of IE; however, longer courses are
and magnetic resonance imaging. required in patients who have prosthetic valves. Clinical
response to therapy should be monitored closely to deter-
Management mine whether antibiotic modication or surgical inter-
Treatment of IE in pediatric patients should be provided vention is necessary.
through collaboration among infectious disease specialists,
cardiologists, and cardiac surgeons. Specic therapy is de- Surgery
termined on a case by case basis and involves the use of Surgical interventions to remove vegetations or replace
antimicrobial agents and, when necessary, surgical inter- valves can be life-saving in the management of certain
vention. The goal of IE therapy involves the eradication cases of IE. Surgery should be considered in patients with
intractable heart failure, prosthetic valve endocarditis,
and uncontrolled infection (persistent fever and positive
blood culture results for more than 5-7 days) and for
those at high risk of embolic events. The America Heart
Association (AHA) has published extensive guidelines for
the antimicrobial and surgical management of IE, which
are the ultimate resource for denitive management de-
cisions. (5)
Prophylaxis
In 2007, the AHA revised the recommendations for anti-
microbial prophylaxis before dental and surgical procedures
for the prevention of IE because current evidence does not
support the widespread use of antimicrobial prophylaxis.
(2) These recommendations advise prophylaxis only to
those patients with the greatest risk of an adverse outcome
from IE, as listed in Table 3.
Figure. Echocardiogram of a 21-month-old girl with Staphy- Antibiotic prophylaxis regimens in those circumstances
lococcus aureus bacteremia. A vegetation is present on the listed are recommended for procedures that have a high
anterior mitral valve. potential to result in bacteremia with organisms associated
with IE. In general, when determining the necessity clindamycin (20 mg/kg) or azithromycin (15 mg/kg)
for IE prophylaxis, the mucosal location of the procedure can be used.
(ie, oropharynx, respiratory, skin, and musculoskeletal),
the risk for resulting bacteremia, and the colonizing organ-
isms must be taken into account. Antibiotic prophylaxis
Prognosis
Despite advances in medicine, IE remains a signicant
is no longer recommended solely for IE prevention for
cause of morbidity and mortality in children, and recov-
gastrointestinal or genitourinary tract procedures. For all
ery from IE depends on the clinical state of the patient,
high-risk procedures, prophylactic antibiotics should be
site of infection, and pathogenic organism. Of the most
given immediately before the procedure or up to 2 hours
common bacteria responsible for IE, S aureus has been
after the procedure.
associated with poorer prognosis. A recent study reported
Pediatricians commonly encounter questions about IE
that with S aureus involvement, 31% of patients had sig-
prophylaxis regarding dental procedures. Although previ-
nicant morbidity and almost 50% died. (6) Fungal IE,
ously recommended with routine teeth cleanings, the
which is more common in patients with prosthetic valves,
new 2007 guidelines only recommend prophylaxis with
has the poorest prognosis of infecting organisms.
dental procedures that involve manipulation of gingival
Complications of IE can cause serious morbidity, and
tissues or perforation of the oral mucosa only for those
in pediatric patients, heart failure is most commonly seen.
patients at high risk, listed in Table 3. For oral medica-
Embolization to any organ can occur, resulting in dam-
tions, amoxicillin (50 mg/kg) is the recommended anti-
age and possible infections at the site. Left-sided (mitral
biotic for these procedures because it covers the most
valve) lesions, large (>10 mm) vegetations, and infec-
likely cause of IE found in the oral mucosa, viridans strep-
tions with S aureus, Candida species, and AACEK are as-
tococci. A single dose is given 30 to 60 minutes before
sociated with a high risk of embolization. Additional
the procedure is performed. In penicillin allergic children,
complications seen in IE include mycotic aneurysms, ab-
scesses that cause complete heart block, meningitis, oste-
omyelitis, renal abscess, and seizures.
streptococci are a common cause of late valve endocardi- Cardiology, Council on Cardiovascular Surgery and Anesthesia, and
tis, which occurs more than 6 months after surgery. the Quality of Care and Outcomes Research Interdisciplinary
Working Group. Circulation. 2007;116(15):17361754
3. Day MD, Gauvreau K, Shulman S, Newburger JW. Character-
istics of children hospitalized with infective endocarditis. Circula-
tion. 2009;119(6):865-870
Summary 4. Levasseur S, Saiman L. Endocarditis and other intravascular
infections. In: Long SS, Pickering LK, Prober CG, eds. Principles
On the basis of strong research evidence, 3 or more and Practice of Pediatric Infectious Diseases. 4th ed. Maryland
blood cultures, with adequate volumes, should be Heights, MO: WB Saunders; 2012:256265
obtained before starting antibiotic therapy to aid in 5. Baddour LM, Wilson WR, Bayer AS, et al; Committee on
the diagnosis of infective endocarditis (IE). (4) Rheumatic Fever, Endocarditis, and Kawasaki Disease; Council on
On the basis of strong research evidence from Cardiovascular Disease in the Young; Councils on Clinical Cardi-
observational studies, antimicrobials are the ology, Stroke, and Cardiovascular Surgery and Anesthesia; Amer-
foundation of IE therapy and should be administered ican Heart Association; Infectious Diseases Society of America.
as soon as possible in patients for whom IE is Infective endocarditis: diagnosis, antimicrobial therapy, and man-
suspected. (7) agement of complications: a statement for healthcare professionals
On the basis of some research evidence and consensus, from the Committee on Rheumatic Fever, Endocarditis, and
only those at high risk for IE (Table 3) should receive Kawasaki Disease, Council on Cardiovascular Disease in the Young,
antimicrobial prophylaxis before dental or surgical and the Councils on Clinical Cardiology, Stroke, and Cardiovas-
procedures. (2) cular Surgery and Anesthesia, American Heart Association: en-
dorsed by the Infectious Disease Society of America. Circulation.
2005;111(23):e394e434
6. Johnson JA, Boyce TG, Cetta F, Steckelberg JM, Johnson JN.
Infective endocarditis in the pediatric patient: a 60-year single-
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1. Which of the following patients is most likely to have infective endocarditis (IE)?
A. A toddler with a bicuspid aortic valve and a new murmur.
B. A 5-year-old with a bicuspid aortic valve, positive blood culture result, and a liver abscess.
C. A 10-year-old with repaired tetralogy of Fallot, fever, glomerulonephritis, and conjunctival hemorrhages.
D. A 2-month-old former 25-week premature infant with fever and 2 blood cultures yielding Streptococcus
viridans.
E. A 12-year-old with a mobile mass on his mitral valve.
3. A 9-year-old febrile child with chest pain and tachycardia had IE associated with a ventricular septal defect
patch when she was 5 years old. Which of the following laboratory tests is most likely to lead to the primary
diagnosis?
A. Transthoracic echocardiography.
B. Three separate blood cultures (5 mL each) performed during a fever spike.
C. Transesophageal echocardiography.
D. Electrocardiography, troponin measurement, and b-natriuretic peptide measurement.
E. Three blood cultures (5 mL each) performed at least 1 hour apart.
5. Which of the following sign or symptom is classic for IE that develops late in the disease?
A. Splenomegaly.
B. New murmur.
C. Small retinal hemorrhages.
D. Malaise.
E. Arthralgia.
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