Infective Endocarditis

Tan Hong-Yong
Department of Diagnosis
Jining Medical College
 Goals for Today
 Recognize the risk factors, signs, and
symptoms of infectious endocarditis.
 Understand the many approaches to
diagnosing infectious endocarditis.
 Anticipate possible complications.
 Appreciate the necessity of rapid
treatment.
 Anatomy of the Heart

 The heart has four valves. In counterclockwise order, they are: the aortic
valve, the tricuspid valve, the pulmonary valve, and the mitral valve.

 The arrows indicate blood flow. Red arrows indicate the flow of oxygen-rich
blood and blue oxygen-poor.

 Unable to facilitate the one-way flow of blood, damaged heart valves hinder
the pumping of blood efficiently throughout the body, leading to congestive
heart failure. This is one reason the mortality rate of IE remains high even
today.
 Infective Endocarditis
 General definitions  Clinical
and epidemiology manifestation

 Pathogenesis  Complication

 Pathophysiology  Diagnosis

 Treatment
What is Infective Endocarditis (IE)?
 IE is a microbial infection of the inner lining of the
heart, the endocardium.

 A vegetation commonly found on the valvular leaflets

is the characteristic lesion of IE.

 The incidence of IE in the United States is between

10,000 and 20,000 cases per year.

 While incidence has remained steady over the past five

decades, the disease has evolved drastically.

 The mortality rate of IE is 25%.

What are the causative agents?
 Principle causative agents include:
 Streptococci
 Represent approximately 50% of cases of IE – down
from 80% in the preantibiotic era
 Viridans streptococci (30-40% of Streptococcal IE)
 S. bovis account for 40%-50% of Native valve
Endocarditis
 Enterococci
 Cause 5-15% of cases of IE
 Staphylococci
 Responsible for about 20% of cases of IE
 Coagualse-negative staphylococci (e.g. S. aureus) cause
60% of prosthetic-valve IE
 Mortality rates in prosthetic valve endocarditis have
been decreasing, although the mortality rates of IE due to
S. aureus remain ominously high.
 S. bovis
 Streptococcus bovis is a catalase- and
oxidase-negative, non-motile,
Gram-positive lactic acid bacterium that
grows as pairs or chains of cocci.It is
commonly found in the alimentary tract of
cows, sheep, and other ruminants
 S. aureus
 S. aureus is a facultative anaerobic Gram-
positive coccus. Under the microscope they
usually appear as grape-like clusters. They
can be found in the air, dust, water and
human faeces. S. aureus can cause a range
of illnesses from minor skin infections, such
as pimples, abscesses, to life-threatening
diseases such as pneumonia, endocarditis,
Toxic shock syndrome (TSS), and septicemia
. Its incidence is from skin, soft tissue,
respiratory, bone, joint, endovascular to
wound infections.
 Less prevalent causative agents
include:
 Other bacteria
 The HACEK Group
 Usual bacterial causes
 Clostridium, tuberculosis, etc.
 Fungi
 Candida and Aspergillis species

(A number of organisms on this list are

responsible for culture-negative IE)
 HACEK
 A HACEK organism is one of a set of
slow-growing Gram negative bacteria
that form a normal part of the human
flora.
 They are a frequent cause of
endocarditis in children.
Who is susceptible to IE?
Infective Endocarditis requires bacteremia and quite often
requires an underlying heart defect to be exploited by the
blood-borne pathogens.

With this in mind, the following groups of people are

more susceptible to IE:

 People with congenital heart defects

 People who have had rheumatic fever
 The elderly
 Intravenous drug users
 People with compromised immune systems
 AIDS patients
 Cancer patients
 Pathogenesis
 At a previously-damaged cardiac valve, a jet
stream of blood with an abnormally high velocity
damages the endothelium

 This damaged surface becomes a starting point

for the deposition of platelets and the formation of
a platelet-fibrin clot, causing nonbacterial
thrombotic endocarditis (NBTE).

 IE develops after bacteria enter the bloodstream

and colonize the clot.
Not every incidence of bacteremia leads to IE. Not only must
the blood-borne pathogen be present in significant enough
numbers to establish infection, it must possess the capacity
(determinants of virulence) necessary to adhere to and colonize
the damaged endothelium.
 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.
 Pathogenesis
 Platelets and fibrin accumulate over the
bacteria, increasing the size of the
vegetation.
 Leukocytes are unable to penetrate the
vegetation as additional layers of fibrin
are added. Treatment with antibiotics
can also be problematic because the
bacteria within the vegetation often
become less metabolically active, and
many antibiotics require active bacterial
growth to be effective.
 The Venturi Principle
 Explains the distribution of lesions on different valves
 For example, when infected blood flows from a high-pressure
area (e.g. the left ventricle) through an orifice (the improperly-
sealed mitral valve) and into a low-pressure sink (the atrium), a
Venturi effect is created. Pathogens may become engrafted on
the atrial side of the mitral valve.

 A regurgitant (surging) bloodstream damages the endocardium.

 But that’s not all…
 The mechanisms just described pertain to
subacute IE

 50-60% of cases of acute IE do not require

underlying heart damage.

Being highly virulent, the organisms most

responsible for acute IE (e.g. S. aureus) are able
to colonize normal heart valves.

 The incidence of acute IE has been steadily

rising and now exceeds the number of subacute
IE cases.
 Pathophysiology
 Turbulent blood flow disrupts the
endocardium making it “sticky”
 Bacteremia delivers the organisms to
the endocardial surface
§ Adherence of the organisms to the
endocardial surface
§ Eventual invasion of the valvular
leaflets
 Pathophysiology
 Local destructive effects
 Valvular destruction
 Chordal rupture
 Perforation/fistula formation
 Paravalvular abscess
 Conduction abnormalities
 Purulent pericarditis
 Functional valve obstruction
 Clinical profile
 Classification
 Duke Criteria
 The Essential Blood Test
 Imaging
 Symptoms and signs
 Complications
 Classification:
 Acute vs. subacute
 Discouraged…

 Causative agent

 Native valve vs. prosthetic valve

 Early prosthetic valve endocarditis vs. Late
PVE
 Right-sided vs. left-sided

 Culture-positive vs. culture-negative

 Modified Duke Criteria
 Definite IE
 Microorganism (via culture or histology) in a valvular
vegetation, embolized vegetation, or intracardiac abscess
 Histologic evidence of vegetation or intracardiac abscess

 Possible IE
 2 major
 1 major and 3 minor
 5 minor

 Rejected IE
 Resolution of illness with four days or less of antibiotics
The Duke Criteria
 The Essential Blood Test
 Blood Cultures
 Minimum of three blood cultures
 Three separate venipuncture sites
 Obtain 10-20mL in adults and 0.5-5mL in children
 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 a more positive blood cultures in which the first
and last samples were collected at least one hour apart
 Additional Labs
 CBC: increase of WBC count
 ESR and CRP: elevated levels
 RF: (+)
 Urinalysis: hematuria or proteinuria
 Imaging
 Chest x-ray
 Look for multiple focal infiltrates and
calcification of heart valves
 EKG
 Rarely diagnostic
 Look for evidence of ischemia, conduction
delay, and arrhythmias
 Echocardiography
 Echocardiography

 Types include:
 Transthoracic echocardiogram (TTE)
 Transesophageal echocardiogram
(TEE)
 The “gold standard”
The figure on the left is of a mitral valve vegetation shown
by echocardiogram.

The figure to the right shows one portion (called a leaflet)

of the mitral valve.
 Imaging
 Cardiac catheterization: Discouraged…

 Coronary Angiography
for those over 55ys or high risk for
coronary artery disease based on their
coronary factors.
Clinical manifestation
 Presenting symptoms and clinical features
include:
 Fever
 Malaise
 Fatigue
 Anorexia: no appetite
 Weight loss
 Splenomegaly
 Cardiac murmur
 Petechiae
 Roth spots
 Janeway lesions
 Osler nodes
Some of the more diagnostic symptoms (the latter half of the above list)
are occurring less frequently in patients with subacute IE, making
diagnosis a greater challenge.
 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
 Petechiae
1. Nonspecific
2. Often located on extremities
or mucous membranes
 Splinter Hemorrhages

• Nonspecific
• Nonblanching
• Linear reddish-brown lesions found under the nail bed
• Usually do NOT extend the entire length of the nail
 Janeway Lesions

1. More specific
2. Erythematous, blanching macules
3. Nonpainful
4. Located on palms and soles
Subconjunctival Hemorrhages
Roth Spots

retinal
hemorrhages
with white or
pale centers
composed of
coagulated
fibrin.
 Complications
 Systemic emboli
 Incidence decreases with effective anti-microbial Rx
 Neurological sequelae
 Embolic stroke 15 – 20% of patients
 Mycotic aneurysm
 Cerebritis
 CHF
 Due to mechanical disruption
 High mortality without surgical intervention
 Renal insufficiency
 Immune complex mediated
 Impaired hemodynamics/drug toxicity
 Complications
 Congestive heart failure is only one aspect of IE that
explains the high mortality rate.

 When the vegetations grow as the infection proceeds, small

pieces may break off, travel through the blood, and become
lodged in other locations throughout the body. These
locations include:
 The intestines
 The lungs
 The kidneys
 The liver
 The brain

 Systemic embolization is found in 22-50% of cases of IE.

How is IE diagnosed?
 Modified Duke Criteria
 Definite IE
 Microorganism (via culture or histology) in a valvular
vegetation, embolized vegetation, or intracardiac abscess
 Histologic evidence of vegetation or intracardiac abscess

 Possible IE
 2 major
 1 major and 3 minor
 5 minor

 Rejected IE
 Resolution of illness with four days or less of antibiotics
The Duke Criteria
How is IE treated?
 Antimicrobial Therapy
 Antibiotics are usually administered intravenously for 2-6
weeks. Duration depends on the virulence of the pathogen.

 The drug of choice for most cases of viridians streptococcal

endocarditis is penicillin.
 The cure rate for viridans streptococcal endocarditis is above 90%.
 Without treatment, VSE is typically fatal within six months.

 Antifungals alone are not enough to cure fungal IE, although

Amphotericin B is often administered in conjunction with
surgery.
Antimicrobial Therapy
Antimicrobial Therapy
Antimicrobial Therapy
Antimicrobial Therapy
 Surgical Treatment
 15-25% of patients with IE are treated surgically

 When removal of an infected valve is necessary:

 Antibiotic therapy fails (first reported case: 1965)
 Persistent vegetation after systemic embolization
 Increase in vegetation size after antimicrobial therapy
 Valvular dysfunction
 Fungal endocarditis

 “The surgeon wields a double-edged scalpel”

 Surgery can introduce organisms and initiate an infection

 50% of some valvular infections do not respond to

antimicrobial therapy or surgery
 Today’s highly virulent causative agents have led to an
increase in dangerous complications
Can IE be prevented?
 Prevention
 Prophylaxis
 Antibiotics may kill blood-borne bacteria or
interfere with their metabolism, hindering their
ability to adhere to a damaged heart valve
 Controversial
 Antibiotic resistance is increasing
 Only administered prior to “high risk” surgeries
 Include dental procedures, surgery on the
gastrointestinal or urinary tract, surgery on infected
tissues

 Talk to your doctor

 Practice good oral hygiene

 Chemoprophylaxis
Adult Prophylaxis: Dental, Oral, Respiratory, Esophageal
Standard Regimen

Amoxicillin 2g PO 1h before procedure or

Ampicillin 2g IM/IV 30m before procedure
Penicillin Allergic
Clindamycin
600 mg PO 1h before procedure or
600 mg IV 30m before
Cephalexin OR Cefadroxil 2g PO 1 hour before
Cefazolin 1.0g IM/IV 30 min before procedure
Azithromycin or Clarithromycin 500mg PO 1h before
Adult Genitourinary or Gastrointestinal Procedures
High Risk Patients
Standard Regimen
Before procedure (30 minutes):
Ampicillin 2g IV/IM AND
Gentamicin 1.5 mg/kg (MAX 120 mg) IM/IV
After procedure (6 hours later)
Ampicillin 1g IM/IV OR
Amoxicillin 1g PO
Penicillin Allergic
Complete infusion 30 minutes before procedure
Vancomycin 1g IV over 1-2h AND
Gentamicin 1.5 mg/kg IV/IM (MAX 120 mg)

Moderate Risk Patients

Standard Regimen
Amoxicillin 2g PO 1h before OR
Ampicillin 2g IM/IV 30m before
Penicillin Allergic
Vancomycin 1g IV over 1-2h, complete 30m before
 Poor Prognostic Factors
 Female  Diabetes mellitus
 S. aureus  Low serum albumen
 Vegetation size  Apache II score
 Aortic valve  Heart failure
 Prosthetic valve  Paravalvular
 Older age abscess
 Embolic events
 Case: History
 2 wks of high fever, cough, green
sputum, and dyspnea on exertion.
 2 wks of nausea and vomiting (5x/day),
diarrhea (20x/day), and diffuse
abdominal pain.
 Last IVDA 3 wks ago.
 Case : History
 Which symptoms does this Patient
have that suggest IE?

 Does this Patient have any symptoms

you can’t explain?
 Case : Exam
 Vitals: T 38.7, BP 100/50, HR 130, RR 48, 94%
on finger tip
 Pale, distressed
 Petechia to palate, dry mucus membranes
 2/6 SEM at 4th intercostal space with radiation
to axilla
 Diffuse wheezing and crackles
 Diffuse abdominal pain and right flank pain
without rebound or guarding
 Multiple track marks, otherwise neg. skin
exam
 Case : Exam
 Which signs does Patient C exhibit that
suggest IE?

 Does Patient C have any signs you

can’t explain?
 Case : Labs
 WBC 20, Platelets 66
 pH 7.45, pO2 54, pCO2 27
 Albumen 28
 UA: 2+ protein,3+ blood
 EKG: within normal limits except sinus
tachycardia
 CXR: enlarged right heart, bilateral infiltrates
with nodularity
 Chest CT: multiple pulmonary abscesses
 Case : Labs
 Can you explain these results?

 Are there other lab values you would

like to know?
 Case : Diagnosis
 Blood Cx: three out of three bottles grew MRSA.

 Initial TTE: tricuspid valve not well visualized but

severe regurg. with PA systolic pressure of 55
mmHg.

 Repeat TTE (~2 wks after coding!): oscillating mass

on at least two leaflets of tricuspid valve that
prolapse into R atrium during systole as well as
thickened pulmonary valve with possible vegetation.
 Case : Diagnosis
 What major Duke criteria does this
Patient meet?

 What minor Duke criteria does this

Patient meet?