Infective Endocarditis

Zemene Tigabu
Assistant prof. of pediatrics and
child health
 Outline
– Definition

– Classification

– Epidemiology

– Pathogenesis

– Etiologic agent

– Clinical manifestations

– Diagnosis

– Treatment

– complications

– prevention
 Definition
• Infectious Endocarditis (IE): an infection of the
heart’s endocardial surface
• Classified into four groups:
– Native Valve IE
– Prosthetic Valve IE
– Intravenous drug abuse (IVDA) IE
– Nosocomial IE
 Further Classification
• Acute • Subacute
– Affects normal heart – Often affects damaged
valves heart valves
– Rapidly destructive – Indolent nature
– Metastatic foci – If not treated, usually
– Commonly Staph. fatal by one year
– If not treated, usually
fatal within 6 weeks
 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
IE often occurs when there is an underlying cardiac
abnormality that creates a high-low pressure gradient.
The resultant turbulent blood flow disrupts the endocardial
surface by peeling away the endothelium.
 Location of vegetations
• Vegetations tend to occur when blood travels from an area of
high pressure through a narrow orifice into an area of lower
pressure
• Vegetations in patients with preexisting valvular lesions are
usually located on the atrial surface of incompetent
atrioventricular valves, or the ventricular surfaces of
incompetent semilunar valves.
• Patients with ventricular septal defects tend to develop
vegetations on the orifice of the defect, on the right
ventricular side of the opening, and secondarily on the
tricuspid and pulmonic valves
•
Epidemiology
Incidence difficult to ascertain and varies according to location
• Much more common in males than in females
• May occur in persons of any age and increasingly common in elderly
• Mortality ranges from 20-30%
• There is an estimated 10-15,000 new cases of IE diagnosed in the U.S. each year,
although the exact incidence of IE is difficult to ascertain. IE is a relatively
uncommon disease, is not a reportable disease, and different case definitions have
existed throughout the years. Furthermore, the incidence varies greatly depending
on geographic regions.

• IE is more common among males. The male:female ratio varies from 2:1 to 9:1
depending on the source.

• In the past, IE was a disease of children and young adults. It predominantly

affected children with congenital heart disease and adults with rheumatic heart
disease. Today, IE commonly affects the elderly, with almost 50% of cases in the
U.S. occurring in patients over the age of 60. This may be due to the decreasing
incidence of rheumatic heart disease and the increasing proportion of elderly in
the U.S.

• Mortality from IE remains high, and ranges from 20-30% despite newer antibiotics
and surgical options.
 Risk Factors
• Intravenous drug abuse
• Artificial heart valves and pacemakers
• Acquired heart defects
– Rheumatic heart disease
– Calcific aortic stenosis
• Congenital heart defects
– VSD
– PDA
– Coarctation
– TOF
– Mitral valve prolapse with regurgitation
• Intravascular catheters
• The top three risk factors for IE include, IVDA,
prosthetic heart valves, and structural heart disease.
• IVDA – one large study of IVDAs found that the use
of cocaine was associated with a higher risk of IE
than other injectable drugs. The most significant risk
factor for right-sided IE is IVDA, although left sided
disease is quite common among IVDAs. The most
common infecting organism is clearly S. aureus,
particularly in right-sided infection.
• Prosthetic valve IE comprises a small proportion of
all cases of IE and occurs in only 1% of all patients
with artificial heart valves. The greatest risk is in the
first year following valve replacement.
 .
• Structural heart disease – approximately ¾ of all cases of IE
occur in patients with preexisting structural heart
abnormalities. The most common underlying heart
abnormalities include mitral valve prolapse with mitral
regurgitation and aortic stenosis.
• The most common congenital heart defects include
Tetralogy of Fallot, bicuspid aortic valves, coarctation of
the aorta, VSDs, and patent ductus arteriosus. In general,
the higher the gradient of the valvular insufficiency, the
higher the risk of IE.
• One of the greatest risk factors of all is a prior episode of
IE.Some studies have documented recurrence as high as
9%.
 Infecting Organisms
• Common bacteria
– Viridans group streptococci (S. mutans, S. sanguis, S. mitis)
– Staphylococcus aureus
– Group D streptococcus (enterococcus) (S. bovis, S. faecalis)
• Not so common bacteria
– Pseudomonas
– HACEK
• Fungi

Staphlococcal and Streptococcal organisms comprise over 80% of all

infecting organisms.
 Symptoms
• Acute • Subacute
– High grade fever and chills – Low grade fever
– SOB – Anorexia
– Arthralgias/ myalgias – Weight loss
– Abdominal pain – Fatigue
– Pleuritic chest pain – Arthralgias/ myalgias
– Back pain – Abdominal pain
– N/V

The onset of symptoms is usually ~2 weeks or less

from the initiating bacteremia.
 Signs
• Fever
• Heart murmur( new or changing murmur)
• Nonspecific signs – petechiae, subungal or
“splinter” hemorrhages, clubbing,
splenomegaly, neurologic changes
• More specific signs - Osler’s Nodes, Janeway
lesions, and Roth Spots
 Petechiae
1. Nonspecific
2. Often located on extremities
or mucous membranes
dermatology.about.com/.../
blpetechiaephoto.htm

Harden Library for the Health Sciences

Photo credit, Josh Fierer, M.D. www.lib.uiowa.edu/ hardin/
medicine.ucsd.edu/clinicalimg/ Eye-Petechiae.html md/cdc/3184.html
 Splinter Hemorrhages

1. Nonspecific
2. Nonblanching
3. Linear reddish-brown lesions found under the nail bed
4. Usually do NOT extend the entire length of the nail
Subungal hemorrhages that extend the entire length of the
nail or are primarily located at the proximal end of the nail
(near the cuticle) are like due to trauma.
 Janeway lesions
American College of Rheumatology
webrheum.bham.ac.uk/.../ default/pages/3b5.htm www.meddean.luc.edu/.../
Hand10/Hand10dx.html

1.Erythematous, blanching macules

2.Nonpainful
3.More specific
4.Located on palms and soles
 Osler’s Nodes

1. More specific
2. Painful and erythematous nodules
3. Located on pulp of fingers and toes
4. More common in subacute IE
 The Essential Blood Test
• Blood Cultures
– Minimum of three blood cultures1

– Three separate venipuncture sites

– Obtain 10-20mL in adults and 0.5-5mL in children2

• 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 more positive blood cultures in which the first and last
samples were collected at least one hour apart
• If you suspect the pt has subacute IE or is not critically ill,
then the three samples can be collected over 24-72 hours
and antibiotics can be held until all three samples have
been drawn.
• However, if the pt is acutely ill, critical, or unstable, the
three cultures should be obtained over a 1 hour time span
before beginning empiric therapy.
• There is no need to collect anaerobic blood cultures since
virtually all cases of IE are caused by aerobic organisms.
• There is little additional diagnostic yield to collecting more
than three blood cultures unless the pt was previously on
antibiotics. In one study of 206 cases of IE, the initial
blood culture was positive in 96% of streptococcal IE and
one of the first two cultures were positive 98% of the
time. For pt’s with IE cause by organisms other than
strep, one of the first two blood culture was positive in
100% of the cases.
• The estimated diagnostic yield of a blood
culture increases by about 3% per mL of blood
cultured. One study found that the detection
rate for bacteremia increased from 69% to
92% when at least 5mL of blood were used for
culture.
• The most common cause of negative cultures
in patients with IE is prior antibiotic use.
 Additional Labs

• CBC – Look for a normochromic normocytic anemia and/or a leukocytosis.

• ESR and CRP - Look for an elevated erythrocyte sedimentation rate and/or
an elevated C-reactive protein which are present 90-100% of the time.

• RF - Occasionally there will be an elevated levels of Rheumetoid Factor,

particularly in patients who have been infected for six weeks or more.
(Minor Duke’s Criteria)

• UA - Urinalysis may reveal microscopic or gross hematuria, proteinuria,

and pyuria. These findings along with a low serum complement level
indicate a glomerulonephritis or “immunologic phenomena”. (Minor
Duke’s Criteria)
• Complement levels (C3, C4, CH50)
• Baseline chemistries and coagulation tests
 Imaging
• Chest x-ray
– Look for multiple focal infiltrates and calcification of heart valves
– A chest xray can contain multiple diagnostic clues such as calcification of
heart valves, which should raise suspicion in a febrile patient without an
obvious source. More commonly, the chest xray may reveal septic
pulmonary emboli in a patient with right-sided IE (Minor Duke’s Criteria).

• EKG
– Rarely diagnostic
– Look for evidence of ischemia, conduction delay, and arrhythmias
An EKG alone cannot diagnose IE but it may show evidence of some of the
disease’s complications. For example, EKG with ST changes may indicate
ischemia or infarction from septic emboli. Arrhythmias such as heart block may
indicated extension of the infection from the valves into the septum and
surrounding cardiac tissue.
-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
• TTE and TEE are complementary for evaluating cardiac hemodynamics and anatomy,
but TEE has superior sensitivity, especially in detecting native valve vegetations,
prosthetic valve vegetations, and local extension of infection. However, it is
significantly more expensive and invasive.

• If there is any suspicion of IE, get a TTE.

• if there is staph or fungal bacteremia, a TEE should probably be obtained.
• If there is a high clinical suspicion for IE and the TTE is negative, you should proceed to
a TEE.
• If there is a concern for intracardiac complications, a TEE is warranted.
• It’s important to remember that the negative predictive value of a TEE is between 96-
98%, meaning that a TEE cannot definitively rule out endocarditis. If the initial TEE is
negative in a patient with a high clinical suspicion for IE, a repeat examiniation should
be done if the pt does not improve.
 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”
• Pelletier and Petersdorf criteria – 3 case categories:
• Definite – histologic evidence of endocardial vegetations
on examination of tissue
• Probable - uniformly positive blood cultures with know
underlying heart disease or embolic phenomena OR
negative blood cultures in pts with fever, new regurgitant
valvular heart murmur, and embolic phenomena
• Possible - uniformly positive blood cultures with know
underlying heart disease or embolic phenomena OR
negative blood cultures with fever and known underlying
heart disease and embolic phenomena
• Von Reyn criteria – modified the above criteria to improve
specificity and clinical utility.
• Duke Criteria – relies upon major and minor clinical and
pathologic criteria to classify cases as definite, possible,
and rejected
 Modified Duke Criteria
• Definite IE
– Pathologic criteria
• Microorganism: (via culture or histology) in a valvular vegetation,
embolized vegetation, or intracardiac abscess
• Pathological lesions: vegetation or intracardiac abscess present,
confirmed by histology showing active endocarditis
– Clinical criteria
• Two major criteria, or
• One major and three minor criteria, or
• Five minor criteria

Multiple studies have validated the Duke criteria. When applied and
reapplied over the entire evaluation, these criteria are sensitive and
specific and very rarely erroneously reject a true endocarditis.
 Con’d
• Possible IE
 One major criterion and one minor criterion or three minor
criteria
• Rejected IE
 Firm alternative diagnosis for manifestations of endocarditis, or
 Sustained resolution of manifestations of endocarditis, with
antibiotic therapy for 4 days or less, or
 No pathological evidence of infective endocarditis at surgery or
autopsy, after antibiotic therapy for 4 days or less
 Con’d
• Major Criteria
 Positive blood culture
– Typical microorganism for infective endocarditis from two separate
blood cultures
– Persistently positive blood culture, defined as recovery of a
microorganism consistent with infective endocarditis from:
• Blood cultures (≥2) drawn more than 12 hr apart, or
• All of three or a majority of four or more separate blood
cultures, with first and last drawn at least 1 hr apart
– Single positive blood culture for Coxiella burnetii or antiphase I IgG
antibody titer >1:800
 Con’d
 Evidence of endocardial involvement
– Positive echocardiogram
• Oscillating intracardiac mass, on valve or supporting structures,
or in the path of regurgitant jets, or on implanted material, in
the absence of an alternative anatomical explanation, or
• Abscess, or
• New partial dehiscence of prosthetic valve, or
– New valvular regurgitation (increase or change in preexisting
murmur not sufficient)
 Con’d
 Minor Criteria
– Predisposition: predisposing heart condition or intravenous drug use

– Fever ≥38.0°C (100.4°F)

– Vascular phenomena: major arterial emboli, septic pulmonary
infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival
hemorrhages, Janeway lesions
– Immunological phenomena: glomerulonephritis, Osler nodes, Roth
spots, rheumatoid factor
– Microbiological evidence: positive blood culture but not meeting
major criterion as noted previously[*] or serologic evidence of active
infection with organism consistent with infective endocarditis
 Con’d
• The following minor criteria are added to those already listed:
– the presence of newly diagnosed clubbing
– splenomegaly
– splinter hemorrhages, and petechiae
– a high erythrocyte sedimentation rate
– a high C-reactive protein level
– the presence of central nonfeeding lines
– peripheral lines
– microscopic hematuria
 Treatment
• Parenteral antibiotics
– High serum concentrations to penetrate vegetations
– Prolonged treatment to kill dormant bacteria clustered in vegetations
• Surgery
– Intracardiac complications
– intractable heart failure
– failure to sterilize the blood despite adequate antibiotic levels
– increasing size of vegetations while receiving therapy
• Surveillance blood cultures
 PREVENTION

• Antimicrobial prophylaxis before various procedures and

other forms of dental manipulation may reduce the
incidence of infective endocarditis in susceptible patients
 Complications
• Four etiologies
– Embolic
– Local spread of infection
– Metastatic spread of infection
– Formation of immune complexes – glomerulonephritis and
arthritis
 Embolic Complications
• Occur in up to 40% of patients with IE
• Predictors of embolization
– Size of vegetation
– Left-sided vegetations
– Fungal pathogens, S. aureus, and Strep. Bovis
• Incidence decreases significantly after initiation
of effective antibiotics
• Systemic emboli are among the most common
complications of IE, occurring in up to 40% of
patients. Subclinical emboli are often found on
autopsy.
 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)
Septic Pulmonary Emboli

http://www.emedicine.com/emerg/topic164.htm
Septic Retinal Embolus
 Local Spread of Infection
• Heart failure
– Extensive valvular damage
• Paravalvular abscess (30-40%)
– Most common in aortic valve, IVDA, and S. aureus
– May extend into adjacent conduction tissue causing
arrythmias
– Higher rates of embolization and mortality
• Pericarditis
• Fistulous intracardiac connections
 Local Spread of Infection

Acute S. aureus IE with perforation of the Acute S. aureus IE with mitral valve ring
aortic valve and aortic valve vegetations. abscess extending into myocardium.
 Metastatic Spread of Infection
• Metastatic abscess
– Kidneys, spleen, brain, soft tissues
• Meningitis and/or encephalitis
• Vertebral osteomyelitis
• Septic arthritis
 Poor Prognostic Factors
• Female • Diabetes mellitus
• S. aureus • Low serum albumen
• Candida infection • Heart failure
• Vegetation size • Paravalvular abscess
• Aortic valve • Embolic events
• Prosthetic valve
 IE Mortality Rates
• 100% fatal if not treated
• With antibiotic treatment, fatality rate:
– NVE (native valve)
• Streptococcus <10%
• Staphylococcus 25-40%
• Gram negatives 75-83%
• Fungi 50-60%
– Late PVE (prosthetic valve) 30-53%