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infectious diseases

Endocarditis
Leigh Bragg, MD,*
Ana Alvarez, MD*

Author Disclosure
Drs Bragg and Alvarez

Educational Gaps
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)
2. Pediatricians should be aware of the recently revised American Heart Association
recommendations for antimicrobial prophylaxis of infective endocarditis in children. (2)

have disclosed no
financial relationships
relevant to this article.
This commentary does
not contain
a discussion of an
unapproved/
investigative use of

Objectives
1.
2.
3.
4.
5.

a commercial product/

After completing this article, readers should be able to:

List the risk factors for infective endocarditis (IE).


Recognize the signs, symptoms, and Duke criteria that aid in the diagnosis of IE.
Determine the appropriate laboratory tests and imaging necessary to aid in diagnosing IE.
Discuss the medical and surgical management used in the treatment of IE.
Identify the population and procedures in which prophylactic antibiotics are used to
prevent IE.

device.

Case 1
A previously healthy 3-year-old boy presents with 5 days of fever, chills, malaise, and vomiting. On examination, his temperature is 102.4F (39.1C). He is lethargic and has petechiae 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 replacement 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 operating room for valve replacement. Three blood cultures performed before the initiation
of antibiotic therapy yield Streptococcus mitis.

Epidemiology

Abbreviations
AACEK: Aggregatibacter parainuenzae, Aggregatibacter
actinomycetemcomitans, Cardiobacterium
hominis, Eikenella corrodens, and Kingella species
AHA: American Heart Association
CHD:
congenital heart disease
CVC:
central venous catheter
IE:
infective endocarditis
ECHO: echocardiography

Pediatric patients are rarely diagnosed as having infective endocarditis (IE); however, IE is a signicant cause of morbidity and mortality in children. Most often IE is a complication
of CHD, but it can occur in children who do not have a cardiac abnormality. The epidemiology of endocarditis has
changed throughout the years as the prevalence of rheumatic heart disease has decreased and the survival of patients
with CHD and the use of indwelling central venous catheters (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.

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infectious diseases

Traditionally, data from several pediatric studies indicate that most pediatric patients with IE had CHD; however, one study found that 56% of pediatric IE patients
did not have preexisting heart conditions. (3) The increase of IE in children without cardiac abnormalities
in this study was thought to be secondary to the use of
indwelling CVCs and the diverse population studied,
which included children from numerous centers across
the United States. Even though patient characteristics
with IE have evolved, the pathogens associated with IE
in pediatric patients have not changed.

Etiology
The most common organisms responsible for IE in pediatric patients with or without CHD are viridans streptococci and Staphylococcus aureus. Viridans streptococci are
a large heterogeneous group of gram-positive cocci that
are part of the oral microora, and they are commonly
associated with transient bacteremia occurring with dental procedures and even with daily oral hygiene. There are
more than 15 different species in the group (eg, Streptococcus sanguis, S mitis, Streptococcus oralis, and Streptococcus anginosis), and they have been associated with
infection of abnormal valves (CHD or previous acute
rheumatic fever) and with late postoperative endocarditis,
which occurs more than 6 months after cardiac valve surgery. S aureus can cause IE in structurally normal and
abnormal hearts. Although gram-positive bacteria are
the most common pathogens implicated in IE, gramnegative bacteria, better known as AACEK (Aggregatibacter
parainuenzae, Aggregatibacter actinomycetemcomitans,
Cardiobacterium hominis, Eikenella corrodens, and Kingella species) organisms, can cause IE in children. Fungi, most
commonly Candida and Aspergillus, can also be responsible for IE, especially in hospitalized patients who have
prosthetic valves or indwelling CVCs. Culture-negative IE
has been described and occurs in approximately 5% to 10%
of children, less than that seen in adults. (4)

Pathogenesis
Transient bacteremia is thought to originate from a disruption in host mucosal surfaces (oropharynx, gastrointestinal tract, and genitourinary tract) heavily colonized
with microora. Dental procedures and daily activities,
such as chewing foods and brushing teeth, have been implicated as sources of transient bacteremia.
When bacteremia is present, IE can result from the complex interaction among microorganisms, platelets, and brin at the site of damaged cardiac endothelium. The
endothelium can be damaged from turbulent blood ow

endocarditis

secondary to CHD or from indwelling CVCs. Once the endothelium is damaged, platelets and brin are deposited on
its surface, forming a nonbacterial thrombotic endocarditis.
The thrombus is then colonized by microorganisms invading the bloodstream, creating an infected vegetation.
Bacterial pathogens (streptococci and staphylococci
spp) have unique surface components that facilitate attachment to the surface of damaged endothelium. Once
attached to the vegetation, the bacteria are further covered with brin and platelets, thus evading host defense
mechanisms and allowing rapid multiplication. Foreign
valves, pacemaker wires, and CVCs can also develop biolms on the surface where pathogens can adhere and
replicate.

Clinical Manifestations
The clinical presentation of pediatric IE can be classied as
either a subacute or acute process. Subacute presentation
typically manifests as nonspecic symptoms for several
weeks, whereas acute IE generally presents as a rapidly progressive serious illness. Patients can have mixed features,
and the most common signs and symptoms are listed in
Table 1. Children rarely have the classic signs of IE that
develop late in disease, such as Roth spots (small retinal
hemorrhages), Janeway lesions (small, painless, hemorrhagic lesions on the palms and soles), Osler nodes (small,
tender, intradermal nodules on the ngers and toes), and
splinter hemorrhages (linear streaks beneath the nail beds).
Pediatricians should be familiar with the manifestations of
IE in children so that a prompt diagnosis can be attained.

Common Manifestations of
Pediatric Infective Endocarditisa

Table 1.

Manifestation

Frequency, %

Symptoms
Fever
Malaise
Anorexia
Heart failure
Arthralgia
Signs
Splenomegaly
Embolic phenomenon
Murmur (new or changing)
Petechiae

75100
5075
2550
2550
1750
5075
2550
2150
2150

Adapted from Levasseur S, Saiman L. Endocarditis and other


intravascular infections. In: Principles and Practice of Pediatric
Infectious Diseases, 4th ed, Long SS, Pickering LK, Prober CG, eds.,
256-265. Copyright Saunders Elsevier (2012).

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infectious diseases

Table 2.

endocarditis

Modified Duke Criteria for the Diagnosis

of IE

Definite IE
Pathologic Criteria
1. Microorganisms demonstrated by culture or histologic testing in a vegetation,
embolized vegetation, or intracardiac abscess; or
2. Pathologic lesions (vegetation or intracardiac abscess) with active endocarditis
confirmed by histologic testing
Clinical Criteria: 2 major criteria, 1 major and 3 minor criteria, or 5 minor criteria
Major Criteria
1. Positive blood culture result for IE
a. Typical microorganism consistent with IE from 2 separate blood cultures:
i. Viridans streptococci
ii. Streptococcus bovis
iii. AAECK group
iv. Staphylococcus aureus
v. Community-acquired enterococci (without a primary focus)
b. Microorganism consistent with IE from blood cultures with persistently positive
results if:
i. At least 2 positive results of blood cultures sampled more than 12 hours apart
ii. All 3 or a majority of more than 4 blood cultures
c. Single positive blood culture for Coxiella burnetii or IgG antibody titer >1:800
2. Evidence of endocardial involvement by echocardiogram result positive for IE,
defined as:
a. Oscillating intracardiac mass on valve or supporting structures in the path of
regurgitant jets or on implanted material
b. Abscess
c. New partial dehiscence of prosthetic valve
d. New valvular regurgitation (worsening or changing of preexisting murmur not
sufficient)
Minor Criteria
1. Predisposing heart condition or intravenous drug abuse
2. Fever: temperature 100.4oF (38oC)
3. Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic
aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions
4. Immunologic phenomena: glomerulonephritis, Osler nodes, Roth spots,
rheumatoid factor
5. Microbiologic evidence: positive blood culture result but does not meet major
criteria or serologic evidence of active infection with organism consistent with IE
Possible IE
1. 1 Major criterion and 1 minor criterion
2. 3 Minor criteria
Rejected
1. Firm alternative diagnosis for manifestations of endocarditis
2. Resolution of endocarditis manifestations with antibiotic therapy 4 days
3. No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for 4 days
4. Does not fulfill criteria above
AAECKAggregatibacter parainuenzae, Aggregatibacter actinomycetemcomitans, Cardiobacterium
hominis, Eikenella corrodens, and Kingella species; IEinfective endocarditis.
a
Modied from Li JS, Sexton DJ, Mick N, et al. Proposed modications to the Duke criteria for the diagnosis
of infective endocarditis. Clin Infect Dis. 2000;30(4):633-638. By permission of Oxford University Press.

of IE is frequently based on a high


index of suspicion because the clinical presentation is often nonspecic.
The Duke criteria serve as a clinical
guide to aid in the diagnosis of IE
and have been validated and modied to increase sensitivity. As indicated in Table 2, the Duke criteria
consist of pathologic, clinical, laboratory, and ECHO criteria used to
establish the likelihood of IE. Collaboration among pediatricians, cardiologists, and infectious disease
specialists is critical in the diagnosis
and treatment of IE because of the
diverse clinical presentation, need for
prolonged therapy, and potentially
fatal outcomes.

Laboratory Tests
Blood cultures are the most important
laboratory test for the diagnosis of IE
because identication of a pathogen is
critical in the selection of appropriate
antimicrobial therapy. Because IE can
be caused by organisms found on the
skin, it is important to obtain 3 or
more cultures on separate occasions
to reduce the likelihood of contamination. It is imperative to obtain adequate volumes of blood in aerobic
and anaerobic culture bottles to detect pathogens in patients who have
a low level of bacteremia. For small
children, 3 to 5 mL per bottle is recommended; for larger children, 10 mL
per bottle. (4)
Other nonspecic laboratory ndings can be present, including increased erythrocyte sedimentation
rate, anemia, positive rheumatoid factor, hematuria, and low complement.
Elevated b-natriuretic peptide and
troponin I levels can indicate cardiac
injury.

Diagnosis

Imaging

IE is a complex syndrome that requires the presence of


multiple ndings to establish the diagnosis. Identication

ECHO is the primary imaging modality used in the diagnosis and treatment of IE. ECHO should be performed

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infectious diseases

when there is a high index of suspicion for IE, especially


in patients with CHD or indwelling CVCs who have persistent bacteremia. It allows visualization of the abnormalities listed in the Duke criteria: vegetations, abscesses, or
prosthetic valve dehiscence (Figure). It also allows monitoring of abnormalities and cardiac function. In contrast to
adults, transthoracic ECHO is highly sensitive in pediatric
patients and is most commonly used. Transesophageal
ECHO is more invasive but can be used to evaluate patients with complex heart disease or when there is poor visualization with transthoracic ECHO. Although ECHO is
a useful diagnostic tool for IE, vegetations are not always
visualized early in the disease, and their absence does not
rule out IE. If there is a continued suspicion for IE,
ECHO should be performed again in 7 to 10 days.
In patients who have denite IE, ECHO is essential to
monitor heart function and the presence and size of vegetations during therapy and to determine the risk of embolization. Other imaging modalities have been introduced
but are not yet widely used for diagnosing IE in pediatrics.
These modalities include cardiac computed tomography
and magnetic resonance imaging.

Management
Treatment of IE in pediatric patients should be provided
through collaboration among infectious disease specialists,
cardiologists, and cardiac surgeons. Specic therapy is determined on a case by case basis and involves the use of
antimicrobial agents and, when necessary, surgical intervention. The goal of IE therapy involves the eradication

endocarditis

of offending agents which typically requires prolonged


courses of antibiotics.

Antibiotic Therapy
To prevent further endocardial damage and complications,
it is imperative that antibiotic therapy be initiated promptly
in patients with suspected IE. Antibiotic regimens for IE
are based on the patients age, clinical presentation, cardiac
status, and organisms most commonly isolated in infections. Intravenous bactericidal antibiotics are necessary
for the treatment of IE, and high serum levels are required
to eliminate bacterial growth at the site of infection.
Before identication of a pathogen and after appropriate volume blood cultures are obtained, empiric vancomycin and gentamicin therapy is recommended because
this regimen provides coverage against the most common
pathogens of IE, S aureus and viridans streptococci. If a
specic pathogen is identied in culture, the antibiotic
regimen can be tailored based on susceptibility proles.
Typically, 4 to 6 weeks of therapy is recommended in
uncomplicated cases of IE; however, longer courses are
required in patients who have prosthetic valves. Clinical
response to therapy should be monitored closely to determine whether antibiotic modication or surgical intervention is necessary.

Surgery
Surgical interventions to remove vegetations or replace
valves can be life-saving in the management of certain
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 decisions. (5)

Prophylaxis

Figure. Echocardiogram of a 21-month-old girl with Staphylococcus aureus bacteremia. A vegetation is present on the
anterior mitral valve.

In 2007, the AHA revised the recommendations for antimicrobial 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.
Antibiotic prophylaxis regimens in those circumstances
listed are recommended for procedures that have a high
potential to result in bacteremia with organisms associated
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infectious diseases

endocarditis

with IE. In general, when determining the necessity


for IE prophylaxis, the mucosal location of the procedure
(ie, oropharynx, respiratory, skin, and musculoskeletal),
the risk for resulting bacteremia, and the colonizing organisms must be taken into account. Antibiotic prophylaxis
is no longer recommended solely for IE prevention for
gastrointestinal or genitourinary tract procedures. For all
high-risk procedures, prophylactic antibiotics should be
given immediately before the procedure or up to 2 hours
after the procedure.
Pediatricians commonly encounter questions about IE
prophylaxis regarding dental procedures. Although previously recommended with routine teeth cleanings, the
new 2007 guidelines only recommend prophylaxis with
dental procedures that involve manipulation of gingival
tissues or perforation of the oral mucosa only for those
patients at high risk, listed in Table 3. For oral medications, amoxicillin (50 mg/kg) is the recommended antibiotic for these procedures because it covers the most
likely cause of IE found in the oral mucosa, viridans streptococci. A single dose is given 30 to 60 minutes before
the procedure is performed. In penicillin allergic children,

Conditions for Which


Prophylaxis for IE Is
Recommendeda
Table 3.

Prosthetic cardiac valve or prosthetic material used for


cardiac valve repair
Previous IE
CHDb
Unrepaired cyanotic CHD, including palliative shunts and
conduits
Completely repaired defect with prosthetic material or
device during the first 6 months after the procedure
Repaired CHD with residual defects at the site or
adjacent to the site of a prosthetic patch or prosthetic
device
Cardiac transplantation recipients who develop cardiac
valvulopathy
CHDcongenital heart disease; IEinfective endocarditis.
a
From Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective
endocarditis: guidelines from the American Heart Association:
a guideline from the American Heart Association Rheumatic Fever,
Endocarditis, and Kawasaki Disease Committee, Council on
Cardiovascular Disease in the Young, and the Council on Clinical
Cardiology, Council on Cardiovascular Surgery and Anesthesia, and
the Quality of Care and Outcomes Research Interdisciplinary Working
Group. Circulation. 2007;116:1736-1754.
b
Antibiotic prophylaxis is no longer recommended for any other form
of CHD, except those listed above.

clindamycin (20 mg/kg) or azithromycin (15 mg/kg)


can be used.

Prognosis
Despite advances in medicine, IE remains a signicant
cause of morbidity and mortality in children, and recovery from IE depends on the clinical state of the patient,
site of infection, and pathogenic organism. Of the most
common bacteria responsible for IE, S aureus has been
associated with poorer prognosis. A recent study reported
that with S aureus involvement, 31% of patients had signicant morbidity and almost 50% died. (6) Fungal IE,
which is more common in patients with prosthetic valves,
has the poorest prognosis of infecting organisms.
Complications of IE can cause serious morbidity, and
in pediatric patients, heart failure is most commonly seen.
Embolization to any organ can occur, resulting in damage and possible infections at the site. Left-sided (mitral
valve) lesions, large (>10 mm) vegetations, and infections with S aureus, Candida species, and AACEK are associated with a high risk of embolization. Additional
complications seen in IE include mycotic aneurysms, abscesses that cause complete heart block, meningitis, osteomyelitis, renal abscess, and seizures.

Case Discussions
Pediatricians must suspect IE in patients with prolonged
fever and evidence of vascular involvement in children
without CHD. The patient in case 1 had bacteremia
exhibited by 3 positive blood culture results for grampositive coccus that was later identied as S aureus. ECHO
assisted in establishing a diagnosis of IE because the patient was found to have a mitral valve vegetation. On the
basis of the positive blood culture results and the ECHO
results, the patient met Duke criteria for denite IE.
S aureus IE is associated with a high mortality and is
the most common cause of IE in patients without CHD.
Having a high index of suspicion and initiating antibiotic
therapy in a timely manner are crucial in the treatment of
these children.
In case 2, the high-risk CHD patient with a bioprosthetic valve had a new-onset diastolic murmur and signs
of heart failure that prompted suspicion for IE. Given her
CHD and bioprosthetic valve, she is at high risk for IE. The
vegetation seen on ECHO veried her diagnosis according
to the Duke criteria, and antibiotic therapy was initiated.
Because of her deteriorating status, she underwent surgical
valve replacement. Histopathologic test results from the
vegetation revealed neutrophils, macrophages, and grampositive cocci, later identied as S mitis. Viridans

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infectious diseases

streptococci are a common cause of late valve endocarditis, which occurs more than 6 months after surgery.

Summary
On the basis of strong research evidence, 3 or more
blood cultures, with adequate volumes, should be
obtained before starting antibiotic therapy to aid in
the diagnosis of infective endocarditis (IE). (4)
On the basis of strong research evidence from
observational studies, antimicrobials are the
foundation of IE therapy and should be administered
as soon as possible in patients for whom IE is
suspected. (7)
On the basis of some research evidence and consensus,
only those at high risk for IE (Table 3) should receive
antimicrobial prophylaxis before dental or surgical
procedures. (2)

References
1. Bernstein D. Infective endocarditis. In: Kliegman RM, Stanton
BF, St. Geme SW, Schor NF, Behrman RE, eds. Nelson Textbook of
Pediatrics. 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:
16221626
2. Wilson W, Taubert KA, Gewitz M, et al; American Heart
Association Rheumatic Fever, Endocarditis, and Kawasaki Disease
Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on
Clinical Cardiology; American Heart Association Council on
Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group. Prevention of
infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic
Fever, Endocarditis, and Kawasaki Disease Committee, Council on
Cardiovascular Disease in the Young, and the Council on Clinical

endocarditis

Cardiology, Council on Cardiovascular Surgery and Anesthesia, and


the Quality of Care and Outcomes Research Interdisciplinary
Working Group. Circulation. 2007;116(15):17361754
3. Day MD, Gauvreau K, Shulman S, Newburger JW. Characteristics of children hospitalized with infective endocarditis. Circulation. 2009;119(6):865-870
4. Levasseur S, Saiman L. Endocarditis and other intravascular
infections. In: Long SS, Pickering LK, Prober CG, eds. Principles
and Practice of Pediatric Infectious Diseases. 4th ed. Maryland
Heights, MO: WB Saunders; 2012:256265
5. Baddour LM, Wilson WR, Bayer AS, et al; Committee on
Rheumatic Fever, Endocarditis, and Kawasaki Disease; Council on
Cardiovascular Disease in the Young; Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia; American Heart Association; Infectious Diseases Society of America.
Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals
from the Committee on Rheumatic Fever, Endocarditis, and
Kawasaki Disease, Council on Cardiovascular Disease in the Young,
and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed 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 singleinstitution review. Mayo Clin Proc. 2012;87(7):629-635

Suggested Reading
Hoen B, Duval X Clinical practice. infective endocarditis. N Engl J
Med. 2013;368(15):1425-1433
Li JS, Sexton DJ, Mick N, et al. Proposed modications to the
Duke criteria for the diagnosis of infective endocarditis. Clin
Infect Dis. 2000;30(4):633638
Penk JS, Webb CL, Shulman ST, Anderson EJ. Echocardiography
in pediatric infective endocarditis. Pediatr Infect Dis J. 2011;30
(12):1109-1111
Rosenthal LB, Feja KN, Levasseur SM, Alba LR, Gersony W,
Saiman L. The changing epidemiology of pediatric endocarditis
at a childrens hospital over seven decades. Pediatr Cardiol.
2010;31(6):813-820

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infectious diseases

endocarditis

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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.
2. In a patient with IE which of the following findings warrant a heart operation?
A.
B.
C.
D.
E.

Tricuspid valve vegetation and severe valve regurgitation.


Mitral valve vegetation, 2 days of positive blood culture results, and fever.
Aortic valve vegetation and osteomyelitis.
Moderate mitral regurgitation, severe exercise intolerance, and tachypnea.
Pulmonic valve vegetation, fever, and fatigue.

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.
C.
D.
E.

Three separate blood cultures (5 mL each) performed during a fever spike.


Transesophageal echocardiography.
Electrocardiography, troponin measurement, and b-natriuretic peptide measurement.
Three blood cultures (5 mL each) performed at least 1 hour apart.

4. Which of the following is most likely to be a presenting sign or symptom of IE?


A.
B.
C.
D.
E.

Vertigo.
Palpitations.
Pallor.
Heart failure.
Vomiting.

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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Endocarditis
Leigh Bragg and Ana Alvarez
Pediatrics in Review 2014;35;162
DOI: 10.1542/pir.35-4-162

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Endocarditis
Leigh Bragg and Ana Alvarez
Pediatrics in Review 2014;35;162
DOI: 10.1542/pir.35-4-162

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