Infective endocarditis

Outcomes
By the end of the session, the students will be able to:
Ø Identify the bacterial causes of: subacute bacterial
endocarditis, acute bacterial endocarditis
Ø Explain the pathogenesis of infective endocarditis
Ø Explain the role of Streptococcus pyogenes in the development
of rheumatic fever
Ø Justify the underlying factors that predispose to the
development of infective endocarditis

Selected Reading sources

1. Jawetz, Melnick, & Adelberg's Medical Microbiology Lang Medical
Books/McGraw-Hill
2. David Greenwood, Rhchard Slack, John Peutherer, Mike barer. Medical
Microbiology. A guide to Microbial Infections: Pathogenesis, Immunity,
Laboratory Diagnosis and Control. 2007. 17th ed. Churchill Livingstone,
Elsivier.
3. Warren Livenson, Review of Medical microbiology & immunology.
 Infective Endocarditis
n Infective endocarditis (IE) is a
serious INFECTION due to invasion of:
- The heart valves OR
- Endothelium of an adjacent large
artery OR The mural endocardium
by a microorganism. myocardium
n This leads to the formation
of vegetation
_r composed of thrombotic
debris and organisms (associated with
destruction of the underlying cardiac
tissues). to bacteria
n The vegetation USUALLY develops on a
heart valve but occasionally appears on
the mural endocardium.
 Etiologic Agent in IE
Streptococci
old
Viridans Strept.
I Enterococci
Other Streptococci

Staphylococci
sphyi r Coagulase +ve
oreus Coagulase -ve Both
415 pm
Stephon
Gm -ve aerobic bacilliWE
Fungi other
not important
Culture Negative
 Classification of Endocarditis
1. Acute vs. Subacute I.E.
Q 1 Drug abusermostly
(A) Acute IE. norm tww
Synonym: acute bacterial endocarditis:
sub 0090 not
- Is a sudden severe INFECTION of
NORMAL cardiac valves caused by
highly virulent organisms.
The most common cause is:
STAPH. AUREUS
 (A) Acute IE:
- Acute IE FREQUENTLY causes
metastatic infection extracardiac in
distant viscera. sub acute non Mets
is
- The acute valvular infection is
difficult to cure with antibiotics and
usually requires surgery.

- Death occurs within days to a few

weeks in many patients with acute IE,
despite treatment.
(B) Subacute IE.
Synonym: subacute bacterial endocarditis. sudden
neg
Slow
n Subacute IE usually has a more indolent course
than acute.
n Subacute IE is often due to streptococci of
LOW VIRULENCE (Strept.viridans is the
most common cause).
n Has low propensity to hematogenous spread to
extracardiac sites. w
Non Mets
n It affects only ABNORMAL heart valves.
n Its course, even in untreated patients, may
extend over many months.
2A in
n Acute n Subacute
n Toxic presentation n Mild toxicity
n Affects normal n Often affects
heart valves damaged heart
valves
n Rapidly progressing
valve destruction n Indolent (slow)
n Commonly Staph. Aureus nature
n Metastatic foci n Commonly Strept.V.
extracardiac n Rarely leads to
metastatic infection
n If not treated,
usually fatal within n If not treated,
6 weeks usually fatal by one
year
 2. Native-valve vs. prosthetic-
valve endocarditis
n Infections also occur on heart valve prostheses, or
on patches (grafts)
n These infections are referred to ‘prosthetic
endocarditis’
(50% Staph. epidermidis & Staph. aureus).
coagulase re to both
n In contrast, the term ‘native-valve Notivepprosth
endocarditis refers to:
- acute or subacute forms of IE
- involving normal or previously damaged NATIVE
cardiac valves .
 3. Right sided vs. left sided
Most77
n Endocarditis can also be classified by the
side of the heart affected.
Ifree removing teeth
catheter prod a bus
n Intravenous drug abusers (IVDA) who inject
their drugs IV may introduce infection which may
travel to the right side of the heart, affecting
the tricuspid valve, and most often caused
by Staphylococcus aureus.

n In other patients without a history of

intravenous exposure, infective
endocarditis is more frequently left-sided.
 Risk Factors
1– Medical procedures associated with
bacteremia (see later). ers
2– History of IV drug abuse (IVDA) ers
3- Prosthetic heart valves ers
5– History of rheumatic heart disease ers
6– Congenital heart disease or malformations cu
7– Acquired structural heart diseases (e.g.):
* Mitral valve prolapse with regurgitation (MVP)
* Valvular stenosis
 1-Medical procedures associated
with bacteremia
re listen
q PROCEDURE OR ACTIONS: AI GI
§ PERIPHERAL intravenous lines or CENTRAL
venous catheters.
§Dental
§ Upper airway - Dental extraction by oral
- Bronchoscopy flora (eg, strept virridans)
- Intubation - Periodontal surgery
- Chewing gum
§ Gastrointestinal -Tooth brushing
- Upper GI endosc.
§Urologic
- Sigmoidoscopy
-Urethral dilatation
- Barium Enema
-Urethral Catheter
- Liver Biopsy
-Cystoscopy
percutaneous
 Pathogenesis
n Valve surface altered through TRAUMA OR
BLOOD TURBULENCE damaging (eroding)
endothelial lining.
– Fibrin and platelets deposited at the damaged
site forming NON bacterial THROMBOTIC
vegetative lesion.

– Transient bacteremia seeds vegetative lesion.

– Bacteria enter exponential growth that is

protected from WBC within the vegetation.

– Bacteria can begin to damage valve and seed

bloodstream (bacteremia)
 The Vegetation
n Platelet fibrin complex provides a
protective environment.
n Phagocytes incapable of entering and
eliminating the seeding bacteria .

n Few inflammatory cells.

n Pathogenic bacteria often induce more

platelet aggregation.

n Colony counts in vegetations 10 9-10 11

bacteria/gm of tissue
 Symptoms
n Acute n Subacute
n High grade fever and n Low grade fever
chills n Anorexia
n Shortness of Breath n Weight loss
n Arthralgias/ myalgias n Fatigue &
n Abdominal pain weakness
n Pleuritic chest pain n Arthralgias/
n Back pain
myalgias
n Abdominal pain
 Signs
n Fever
n Heart murmur

n More specific signs:

- Osler’s Nodes, hand Prim foot
- Janeway lesions,
- Roth Spots avet in
n Nonspecific signs:
- petechiae,
- “splinter” hemorrhages,
rounder nail bed
- clubbing of fingers
- splenomegaly,
- neurologic changes.
1- Petechial hemorrhages, splinter hemorrhages, and
Janeway lesions are complications of endocarditis that are
relatively rare but can occur when vegetations (i.e., septic
emboli) in the heart dislodge from the surface of the heart and
lodge in small vessels, causing necrosis and hemorrhage in
the tissues.
2- Another uncommon extravascular complication, Osler
nodes, occurs when the host’s immune system reacts with
bacteria that cause the endocarditis, resulting in a localized
inflammation of the blood vessels of the fingers and toes.
3- Roth spots may be due to both reasons (1 & 2).
 Osler’s Nodes

www.meddean.luc.edu/.../
Hand10/Hand10dx.html

1. More specific
2. Painful and erythematous nodules
3. Located on palms, pulp of fingers and toes
4. More common in subacute IE
 Janeway Lesions

1. More specific
2. Erythematous, blanching
macules
1. Non painful
a
6181 A kid
2. Located on palms and soles
Roth’s Spots (Retina)
Flame-shaped hemorrhages with pale centers, can be
observed on funduscopic examination of the retina
 Petechiae
1. Nonspecific
2. Often located on extremities
or mucous membranes

Subconjunctival Hemorrhages
Pharyngeal petechiae
 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
 Modified Duke’s Criteria
Major Criteria Minor Criteria
1. Bactaremia by typical 1. Predisposition abnormal
organism
2. Positive echo
III valve or IVDU
2. Fever
Tl
3. Vascular phenomenon
norm 4. Immune phenomena
An
sound 5. Bactaremia from
atypical organism
Ant other
bacteria
Definite Diagnosis = 2 major
1 major+ 3 minor
5 monors
 Laboratory diagnosis of IE
The Essential Blood Test
JE
n Blood Culture: 3
I
ji
Minimum of THREE blood cultures.
n
É
n Three separate venipuncture sites
n Obtain 10-20mL in adults and 0.5-5mL in
children.

n Positive Results:
n Typical organisms present in at least 2
separate samples.

n Persistently positive blood culture.

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be 14
41111 Ab 6 51
 Prevention
n People with heart defects need prophylactic
antibiotics during invasive procedures
n People with known heart defects should be given
prophylactic antibiotics to protect them during dental
surgery and any other invasive procedure that is
likely to cause a transient bacteraemia.
n Prophylactic regimen targeting the
commonly involved organism:
Strep. Viridans
Enterococcus
S. aureus
 Treatment

n A combination antibiotic therapy is

always used in the treatment of
endocarditis and must be given for 4–6
weeks, even if symptoms disappear
prior to that time.

I
 Rheumatic Fever

n Acute rheumatic fever is an autoimmune reaction

with the heart, joints, central nervous system, skin,
and subcutaneous tissues following untreated
pharyngitis caused by Streptococcus pyogenes.
of
complication of
n Acute rheumatic fever is a systemic disease of
childhood,often recurrent that follows group A beta
hemolytic streptococcal (GAS) infection
 Epidemiology
n Ages 5-15 yrs are most susceptible
n Common in 3rd world countries
n Environmental factors-- over crowding,
poor sanitation
n Incidence more during fall ,winter &
early spring
Characteristic Features & cultural
characters of Streptococci
1. Gram-positive cocci,
arranged in chains or
pairs.
2. Facultative anaerobes.
3. Catalase negative (D.D.
staphylococci, positive)

1. Growth requires
enriched media containing
blood or serum & enhanced
by 5%CO2 .
 Lancefield group antigens
re listen
• Cell wall
Carbohydrate
antigens,
A – W (except I & J
= 21 groups)

• Specific Antibodies
are used for
identification of
different species.
 Virulence factors
Streptococci have many virulence
factors; one of them is:
M protein:
• Cell surface protein.
• MOST important virulence factor:
• Allows bacteria to colonize skin.
• Inhibits phagocytosis.
• Immunogenic: 80 M serotypes.

• M protein have an important role in the

pathogenesis of rheumatic fever.
• Strains that produces rheumatic fever - M types l,
3, 5, 6,18 & 24
Streptolysins
Two pore-forming toxins → lyse host cell membranes.

n Streptolysin O (SLO) n Streptolysin S (SLS)

n oxygen labile. n oxygen stable.
n non-immunogenic.
n highly immunogenic.
n induces specific antibodies
(its detection is the basis for
ASO test).

β-haemolysis on blood agar, under aerobic

condition, is due to SLS.
 Pathogenesis

Acute Rheumatic Fever is

caused by:
Immune response against
Strept.pyogenes M antigens that is
similar to heart muscle antigens
(autoimmune mechanism) and the
damage is caused by type II
hypersensitivity.
 Diagnosis of ARF

No single test is pathognomonic.

Diagnosis is based on modified Jones

criteria:
a)Evidence of recent S .pyogenes
infection.
b)Two of the five major criteria ,OR
one major & two minor criteria .
vThe evidence of recent
streptococcal infection
a-History of acute tonsillitis .
B- Positive throat culture ( in 20% of
cases)
C-Elevation of ASO titre (above 200 units).
Test Procedure:
-Toxin + Patient
serum (antitoxin
à 1/2hr à RBCs
suspension à
1/2hr

-Result:
-No hemolysis: +ve
-Hemolysis à -ve

Positive titre:
> 200 IU/mL
 1 I got

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