Ebright: Infective Endocarditis

Question 1

Infective Endocarditis

DEFINITION

Answer 1

Infection of the endocardial surface of the
heart

Implies the physical presence of
microorganisms in the lesion

Question 2

Organism location (6)

Answer 2

• Heart valves (most common)
• Septal defects
• Mural endocardium
• Arterio-venous shunts
• Arterio-arterial shunts (patent ductus arteriosus –
persistent communication between left pulmonary
artery and the descending aorta)
• Coarctation of aorta

Question 3

Epidemiology

Answer 3

• Approximately 1 case per 1000 hospital admissions
• More than 50% of cases are older than 50 years
• Males more commonly affected (ratio 1.7:1)

Question 4

Epidemiology - Valve Involved

Answer 4

Left
• mitral 28-45%
• aortic 5-36%

• mitral/aortic combined 0-35%
• tricuspid 0-6%
• pulmonic <1%

Question 5

Epidemiology - Association with Underlying
Valvular Disease

Rheumatic heart disease:
Congential heart disease:

IE essentially does not occur with:

Answer 5

Rheumatic heart disease (25%)
•mitral most common

Congential heart disease
•patent ductus arteriosus, ventricular septal defect,
coarctation of the aorta, tetralogy of Fallot
•congenitally bicuspid aortic valve (20% of cases >age 60 poor prognosis)

*IE essentially does not occur with secundum atrial
defects (low-pressure shunt; little turbulence)

Question 6

Epidemiology - Association with Underlying Valvular
Disease

“Degenerative” cardiac lesions

Other conditions

Answer 6

“Degenerative” cardiac lesions (30-40% cases without underlying valve disease)
• Ex: calcified mitral annulus, post myocardial infarction, thrombus

• syphilitic heart disease
• arterioatrial fistulas
• hemodialysis shunts/fistulas
• intracardiac pacemaker wires
• intracardiac prostheses
• intravenous drug abuse
• mitral valve prolapse with mitral regurgitation

Question 7

Pathogenesis
What results in deposition of platelets
and fibrin?

Answer 7

Turbulent flow results in deposition of platelets
and fibrin (nonbacterial thrombotic endocarditis).

Question 8

Pathogenesis
Non-bacterial thrombotic endocarditis (NBTE)

What is a prerequisite for bacterial colonization?
Found in:
What are pathogenic mechanisms?
Found most frequently on which side of cardiac valve?
Along what line?

Answer 8

• Alteration of valve surface is prerequisite for bacterial colonization
• Found in many conditions causing acute/chronic illness
• Hypercoagulability and/or endothelial damage are
pathogenic mechanisms
• Found most frequently on low-pressure side of cardiac valve
• Along the line of closure

Question 9

Pathogenesis

Hemodynamic factors

Answer 9

Lesions with high degrees of turbulence readily create conditions that lead to bacterial colonization

*low flow states (secundum atrial defects) rarely associated with IE

Question 10

Pathogenesis
Transient bacteremia:

Where does it occur?
How long does it usually take to clear the bloodstream?
What can the bacteria in the bloodstream then do?

Answer 10

• Occurs when mucosal surface heavily colonized with bacteria is traumatized
• Bloodstream is usually clear 15-30 minutes after the procedure
• Bacteria in bloodstream can then colonize NBTE lesions

Question 11

Pathogenesis
Microorganism - NBTE Interaction

How do organisms differ?
What do bacteria do once they bind?
What does vegetation create?

Answer 11

• Organisms differ in their propensity to cause (Infective Endocarditis) IE
• Once bacteria bind they proliferate, causing further platelet –fibrin deposition.
• Vegetation creates an environment of impaired host resistance (bacteria covered by platelets/fibrin)

Question 12

Pathogenesis

Immunopathologic Factors

Answer 12

• Stimulation of humoral and cellular immunity
• Rhematoid factor can be positive
• Antinuclear antibodies can be present
• Circulating immune complexes

Question 13

Pathologic Changes

Vegetation located:
Complications:

Answer 13

Vegetation located along line of closure of valve leaflet

Complications
– valve ring abscess
– perforation of valve leaflet
– myocardial abscesses (20%)
– rupture of chordae tendinae, interventricular
septum, papillary muscle
– valvular stenosis (large lesions)
– myocarditis
– pericarditis
– myocardial infarction (40-60% of autopsied
cases)

Question 14

Vegetations
Pathologic Changes
Kidney

Answer 14

• abscess
• infarction
• glomerulonephritis (focal or diffuse)
secondary to immune complex deposition

Question 15

Pathologic Changes
Mycotic aneurysm:

Usually develop during:
Tend to occur where?
Mechanism leads to:
direct bacterial invasion:
embolic occlusion of:
immune complex deposition:
Clinically silent until:

Answer 15

• Usually develop during active disease, but can occur
months to years later
• tend to occur at bifurcation points
• mechanism leading to aneurysm
• direct bacterial invasion of arterial wall with
abscess formation
• embolic occlusion of vasovasorum
• immune complex deposition with injury to
vessel wall
• Clinically silent until rupture occurs

Question 16

Pathologic Changes

CNS
Spleen
Lung (Rt. Sided)

Answer 16

Central nervous system
• cerebral emboli (1/3 of cases)
•also mycotic aneurysms, cerebritis, abscesses

Spleen
•infarctions common (but usually clinically silent)
•abscesses

Lung (Rt. Sided)
•embolic
•pleural effusion/empyema

Question 17

Pathologic Changes

Skin
Eyes

Answer 17

Skin
•petechiae 20-40%
•Osler’s nodes (immune complex)
•Janeway lesions (septic emboli)

Eyes
•Roth spots

Question 18

Clinical Manifestations

“Incubation period”
Average: Symptom onset to diagnosis

Process contributing to the clinical picture (4)

Answer 18

Clinical Manifestations
“Incubation period” 2 weeks but time from symptom onset to diagnosis averages 5 weeks (and depends on causative organism)

Process contributing to the clinical picture
– infectious process on the valve
– bland/septic emboli to any organ system
– constant bacteremia (with metastatic foci)
– circulating immune complexes

Question 19

Clinical Manifestations

Fever:

Nonspecific Symptoms:

Heart Murmur:

Answer 19

Fever (95%)
• Usually remittent
• absent in: CHF, renal failure, older age,
terminal illness, prior antibiotic therapy

Nonspecific Symptoms
• anorexia, weight loss, fatigue, chills,
weakness, nausea, vomiting, night sweats
• often result in incorrect initial diagnosis

Heart murmur (85%)
(classically a new or changing murmur)

Question 20

Clinical Manifestations

Peripheral manifestations (3):

Answer 20

Peripheral manifestations (50%)
•clubbing 10-20%
•splinter hemorrhages
•petechiae

Question 21

Clinical Manifestations

Osler’s nodes:
Janeway lesions:
Roth spots:

Answer 21

Osler’s nodes: small painful nodular
lesions on the pads of fingers/toes or
thenar eminence 0-25%
(immune complex deposition)

Janeway lesions: hemorrhagic, macular,
painless plaques with predilection for the
palms/soles (emboli)

Roth spots: oval, pale, retinal lesions
surrounded by hemorrhage, usually near
the optic disk

Question 22

Clinical Manifestations
Splenomegaly
Musculoskeletal
Major embolic episode

Answer 22

• Splenomegaly 25-60%
• Musculoskeletal complaints
• Major embolic episode to any organ system

Question 23

Clinical Manifestations

Central Nervous System %?
Major cerebral emboli %?
Subarachnoid hemmorhage due to:
Other 3:

Answer 23

• Central Nervous System 20-40%
• Major cerebral emboli 10-31%
• subarachnoid hemorrhage due to
mycotic aneurysm

• seizures
• cranial nerve palsies
• toxic encephalopathy

Question 24

Clinical Manifestations

Renal failure %

Answer 24

Clinical Manifestations

• Renal failure 25-35%

Question 25

Clinical Manifestations in Injection Drug Users What is the most common valve affected? Often present with what?

Answer 25

``` • tricuspid valve most common • often present with prominent pulmonary findings (septic emboli to lungs) • often occurs on otherwise normal heart valves ```

Question 26

Lab Abnormalities | (4)

Answer 26

``` • Anemia common 70-90%*** • thrombocytopenia 5-15% • leukocytosis 20-30% • sedimentation rate (ESR) nearly always elevated 90-100% ```

Question 27

URINALYSIS Proteinuria:% Microscopic hematuria:% Red Cell Casts:% Others (4)

Answer 27

* proteinuria (50-65%) * microscopic hematuria (30-60%) * red cell casts (12%) * gross hematuria * pyuria * white cell casts * bactiuria

Question 28

Lab Abnormalities Blood culture What is the bacteremia? What occurs in >90% of the cases? Less likely to be positive if: Procedure for collecting blood cultures:

Answer 28

* most important lab test * bacteremia usually continuous * In >90% of cases the first 2 sets of blood cultures drawn will yield the organism responsible * less likely to be positive if patient has received antibiotics in the prior 2 weeks * procedure for collecting blood cultures – 3 sets within 24 hours (3 separate venipunctures)

Question 29

What is the most important lab test?

Answer 29

Blood culture

Question 30

2D Echocardiogram

Answer 30

Can visualize vegetations greater than 2 mm in size

Question 31

Transesophageal echocardiogram (TEE) What does the negative study not include? What are rare? Dependent upon: Valuable to assess: Better than: Are patients with vegetation at increased risk of embolization?

Answer 31

* Negative study does not exclude IE * False-positive results are rare * Dependent upon experience of technician/reader •Valuable to assess local complications of IE (valve ring abscess) * Better for visualizing aortic valve than 2D Echo •Patients with vegetations are not at increased risk of embolization.

Question 32

Diagnosis

Answer 32

Combination of clinical and diagnostic criteria used to classify as definite, possible, or not IE.

Question 33

Streptococcus viridans (Gram-positive cocci) ``` Typically: 80% have: A common cause of what? Comprised of what? Prognosis? Most common cause of endocarditis in pts with: ```

Answer 33

``` • typically subacute • 80% have underlying valve disease • a common cause of IE (dental procedures) • many species comprise the viridans group of Streptococci • good prognosis • most common cause of endocarditis in patients with mitral valve prolapse ```

Question 34

Enterococci (Gram-positive cocci) ``` How common? Easy to treat? Usually acute? Commonness of peripheral manifestations: Seen in what population? ```

Answer 34

• increasingly common cause of endocarditis • very difficult to treat • usually subacute • peripheral manifestations uncommon • seen in older men after genitourinary procedures and young women after obstetrical procedures

Question 35

Streptococcus pneumoniae (Gram-positive cocci) ``` How common? Usually: predilection for: Often in what population: Many have: Outcome: ```

Answer 35

* unusual cause * usually fulminant (suddenly or quickly) * predilection for aortic valve (70%) * often alcoholics * many have meningitis (70%) * poor outcome (50% mortality)

Question 36

Staphylococcus aureus (Gram-positive cocci in clusters) Coagulase +/-? Causes what % of staph endocarditis? Attacks what? Prognosis?

Answer 36

• coagulase-positive staphylococci (S. aureus) • causes 80-90% of cases of Staphylococcal endocarditis • commonly attacks “normal” heart valves (1/3 of cases) • prognosis poor (40% mortality)

Question 37

Staphylococcus aureus More commonly causes what? Metastatic infection to where is common? In what population?

Answer 37

• more commonly causes myocardial abscess, purulent pericarditis, and valve ring abscesses than other causes of IE • metastatic infection to lung, brain, spleen, kidney common • common causes of IE in injection drug users but in IDU has less fulminant course with less mortality

Question 38

Staphylococcus epidermidis (Gram-positive cocci in clusters) Coagulase +/-? Common cause of what? Can cause what in neonates? Prognosis:

Answer 38

• coagulase-negative • common cause of prosthetic valve endocarditis • can cause endocarditis in neonates • medical and/or surgical therapy usually successful

Question 39

Gram-negative bacilli ``` Common? Risks: What is common? Prognosis: Commonly require what? Where? Why? ```

Answer 39

• uncommon but increasing • risks: injection drug users, prosthetic valve recipients, cirrhosis • CHF common • prognosis poor (70-80% mortality) • commonly require early valve replacement, especially left-sided disease due to Pseudomonas spp.

Question 40

“HACEK” Group (“culture-negative endocarditis”) Requires how long to grow? HACEK stands for: Acute? Need to:

Answer 40

• Fastidious; require 2-3 weeks to grow ``` H Haemophilus aphrophilus A Actinobacilus actinomycetemcomitans C Cardiobacterium hominis E Eikenella corrodens K Kingella kingae (and other species) ``` * subacute course * need to alert microbiology lab to supplement media and hold cultures longer

Question 41

Fungi | Risks (4)

Answer 41

• injection drug users • patients after reconstructive cardiovascular surgery • patients after prolonged IV/antibiotic therapy • cure virtually impossible without surgery

Question 42

Therapy ``` Abx: Surgery if (5): ```

Answer 42

• Prolonged course of antibiotics (4-6 weeks) with bactericidal agents directed against the specific pathogen • Surgical intervention indication if: – congestive heart failure unresponsive to medical therapy – greater than 1 major systemic embolic complication – inability to clear organism from blood stream (time varies with organism and antimicrobial used) – prosthetic valve endocarditis, esp. early (usually) – certain hard to cure organisms e.g. fungi, Pseudomonas species

Question 43

DEFINITION

Answer 43

Infection of endocardial surface of the heart | the endothelium

Question 44

PATHOGENESIS

Answer 44

Direct infection of “normal” endothelium by highly virulent organisms (S. aureus) Secondary infection of damaged endothelium and platelet-fibrin thrombus during subsequent bacteremic periods

Question 45

INFECTING ORGANISMS Most common bacteria: Less common:

Answer 45

• Most common are bacteria, such as S. aureus, viridans streptococcus, and enterococcus species (high binding potential) • Less common are other organisms such as HACEK, gram negative bacilli (pseudomonas), pneumococcus, chlamydia, and fungi

Question 46

CLINICAL ILLNESS (3)

Answer 46

1. Local 2. Systemic (constitutional) – Bacteremia – Immunologic 3. Embolic

Question 47

MICROBIOLOGIC DIAGNOSIS

Answer 47

* Persistent, continuous bacteremia | * Blood cultures are “always” positive

Question 48

TREATMENT (3)

Answer 48

1. Deep in vegetation, organisms are metabolically inactive 2. Within the vegetation there is poor nutrient supply and poor blood supply 3. Antibiotics must be bactericidal, high dose, and prolonged