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INFECTIVE ENDOCARDITIS
Contents of Lecture
 Endocarditis
– Definitions
– Epidemiology
– classification
– Pathogenesis
– Clinical Presentations
– Diagnosis
– Complications
– treatment
– prophylaxis
DEFINITION
 Infective Endocarditis (IE) is a microbial
infection of the endocardial (endothelial)
surface of the heart.
 The vegetation is a variably sized amorphous
mass of platelets and fibrin in which abundant
micro-organisms and scant inflammatory cells
are enmeshed.
Braunwald – Heart Disease
ENDOCARDITIS
Characteristic pathological lesion: vegetation,
composed of platelets, fibrin, microorganisms
and inflammatory cells.
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%
Classification
 Acute
– Affects normal heart
valves
– Rapidly destructive
– Metastatic foci
– Commonly Staph.
– If not treated, usually
fatal within 6 weeks
 Subacute
– Often affects damaged
heart valves
– Indolent nature
– If not treated, usually
fatal by one year
Pathogenesis
 ALTERED VALVE SURFACE
– Animal experiments suggest that IE is almost impossible to
establish unless the valve surface is damaged
 DEPOSITION OF PLATELETS AND FIBRIN –
nonbacterial thrombotic vegetation (NBTE)
 BACTERAEMIA – attaches to platelet-fibrin deposits
– Covered by more fibrin
– Protected from neutrophils
– Division of bacteria
– Mature vegetation
Pathogenesis
 Haemodynamic Factors
– Bacterial colonisation more likely to occur
around lesions with high degrees of tubulence
» eg. small VSD, valvular stenosis
– Large surface areas, low flow and low
turbulence are less likely to cause IE
» eg large VSD,
Pathogenesis
 Bacteraemia
– Transient bacteraemia occurs when a heavily colonised
mucosal surface is traumatised
» Dental extraction
» Periodontal surgery
» Tooth brushing
» Tonsillectomy
» Operations involving the respiratory, GI or GU tract mucosa
» Oesophageal dilatation
» Biliary tract surgery
Site of Infection
 Aortic valve more common than mitral
 Aortic:
– Vegetation usually on ventricular aspect, all 3
cusps usually affected
– Perforation or dysfunction of valve
– Root abscess
 Mitral:
– Dysfunction by rupture of chordae tendinae
Nonbacterial thrombotic
endocarditis
Bacteraemia
Turbulent blood flow
traumatises endothelium
Further deposition of
fibrin and platelets
Clinical Manifestations
 Fever, most common symptom, sign
 Anorexia, weight-loss, malaise, night sweats
 Heart murmur
 Petechiae on the skin, conjunctivae, oral
mucosa
 Splenomegaly
 Right-sided endocarditis is not associated with
peripheral emboli/phenomena but pulmonary
findings predominate
CLINICAL MANIFESTATION
SYMPTOMS PERCENT SIGNS PERCENT
Fever
Chills
Sweats
Anorexia
Weight loss
Malaise
Dyspnea
Cough
Stroke
headache
Nausea/vomiting
myalgia/arthralgia
Chest pain
Abdominal pain
Back pain
confusion
80-95
42-75
25
25-55
25-35
25-40
20-40
25
13-20
15-40
15-20
15-30
8-35
5-15
7-10
10-20
Fever
Murmur
Changing/new
murmur
Neurological
abnormalities
Embolic event
Splenomegaly
Clubbing
Peripheral
manifestation
Osler’s nodes
Splinter hemorrhage
Petechiae
Janeway’s lesions
Retinal lesion
80-90
80-95
10-40
30-40
20-40
15-50
10-20
10-20
7-10
5-15
10-40
6-10
4-10
Petechiae—Nonspecific
Splinter Hemorrhages
Nonspecific
Osler’s Nodes--More specific
Painful and erythematous nodules
Janeway Lesions
More specific,Nonpainful
Making the Diagnosis
Diagnosis: Duke Criteria
 In 1994 a group at Duke University
standardised criteria for assessing patients
with suspected endocarditis
 Include
-Predisposing Factors
-Blood culture isolates or persistence of
bacteremia
-Echocardiogram findings with other clinical,
laboratory findings
Duke Criteria
Definite
: 2 major criteria
: 1 major and 3 minor criteria
: 5 minor criteria
: pathology/histology findings
Possible : 1 major and 1 minor criteria
: 3 minor criteria
 Rejected : firm alternate diagnosis
: resolution of manifestations of IE with
4 days antimicrobial therapy or less
Echocardiography
 Trans Thoracic Echocardiograpy (TTE)
– rapid, non-invasive – excellent specificity (98%) but
poor sensitivity
– obesity, chronic obstructive pulmonary disease and
chest wall deformities
 Transesophageal Echo (TOE)
– more invasive, sensitivity up to 95%, useful for
prosthetic valves and to evaluate myocardial
invasion
– Negative predictive valve of 92%
Microbiology is very important
since virulence of the infecting
organism is a significant factor in
determining the success rates of
both medical and surgical
treatment
Microbiology
sx’s<60 d post
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
children2
 Positive Result
– Typical organisms present in at least 2 separate samples
Complications
 Four etiologies
– Embolic
– Local spread of infection
– Metastatic spread of infection
– Formation of immune complexes –
glomerulonephritis and arthritis
Local Spread of Infection
Acute S. aureus IE with
perforation of the
aortic valve and aortic valve
vegetations.
Acute S. aureus IE with mitral
valve ring
abscess extending into
myocardium.
Principles of Medical Management
Sterilization of Vegetations with antibiotics
- prolonged
Slowly metabolising bacteria
due to high density, hence 
sensitivity
- high dose
Bacteria deep inside
vegetations
-bactericidal
Therapy
 Streptococci/Enterococci
– Determine MIC of Penicillin
– Penicillin +/- aminoglycoside
– Ceftriaxone alone
– Vancomycin +/- aminoglycoside
– Cefotaxime/ceftriaxone
 HACEK group
Therapy
 Staphylococci
– Native valve
» Flucloxacillin +/- aminoglycoside
» Vancomycin +/- aminoglycoside/ rifampicin
– Prosthetic valve
» Flucloxacillin + aminoglycoside + rifampicin
» Vancomycin + aminoglycoside + rifampicin
Surgical Therapy
 Indications:
– Congestive cardiac failure
– perivalvular invasive disease
– uncontrolled infection despite maximal antimicrobial
therapy
– Presence of prosthetic valve endocarditis unless late
infection
– Large vegetation
– Major embolus
– Heart block
Surgical Therapy
 The hemodynamic status at the time
determines principally operative
mortality
PROPHYLAXIS
 The pathogenesis of infective endocarditis (IE) is presumed to involve the
following sequence of events
●Formation of a small thrombus on an abnormal endothelial surface
●Secondary infection of this nidus with bacteria that are transiently circulating in
the bloodstream
●Proliferation of bacteria resulting in the formation of vegetations on the
endothelial surface
 Since the occurrence of bacteremia is crucial to the initiation of an episode of IE,
in theory it is reasonable to conclude that preventing or promptly treating
transient bacteremia can prevent the above events.
 Evidence to support antimicrobial prophylaxis for
prevention of endocarditis is weak
 antimicrobial prophylaxis for patients with the highest risk
medical conditions undergoing procedures likely to result
in bacteremia with a microorganism that has the potential
ability to cause bacterial endocarditis
HIGHEST RISK CONDITIONS
 Prosthetic heart valves, including bioprosthetic and homograft valves
 A prior history of IE
 Unrepaired cyanotic congenital heart disease, including palliative shunts and
conduits
 Completely repaired congenital heart defects with prosthetic material or
device, whether placed by surgery or by catheter intervention, during the first
six months after the procedure
 Repaired congenital heart disease with residual defects at the site or adjacent
to the site of the prosthetic patch or prosthetic device
 Valve regurgitation due to a structurally abnormal valve in a transplanted
heart
HIGHEST RISK PROCEDURES
 Dental procedures that involve manipulation of either gingival tissue or
the periapical region of teeth or perforation of the oral mucosa; this
includes routine dental cleaning.
 Procedures of the respiratory tract that involve incision or biopsy of the
respiratory mucosa
 Gastrointestinal (GI) or genitourinary (GU) procedures in patients with
ongoing GI or GU tract infection
 Procedures on infected skin, skin structure, or musculoskeletal tissue
 Surgery to place prosthetic heart valves or prosthetic intravascular or
intracardiac materials
Antibiotic Regimens for Prophylaxis of Endocarditis in Adults with
High-Risk Cardiac Lesions
A. Standard oral regimen
 1. Amoxicillin: 2 g PO 1 h before procedure
B. Inability to take oral medication
 1. Ampicillin: 2 g IV or IM within 1 h before procedure
C. Penicillin allergy
 1. Clarithromycin or azithromycin: 500 mg PO 1 h before procedure
 2. Cephalexinc: 2 g PO 1 h before procedure
 3. Clindamycin: 600 mg PO 1 h before procedure
D. Penicillin allergy, inability to take oral medication
 1. Cefazolinc or ceftriaxonec: 1 g IV or IM 30 min before procedure
 2. Clindamycin: 600 mg IV or IM 1 h before procedure
key Clinical points
 Staphylococci and streptococci account for 80% of cases of infective endocarditis, with
staphylococci currently the most common pathogens.
 Cerebral complications are the most frequent and most severe extracardiac complications.
Vegetations that are large, mobile, or in the mitral position and infective endocarditis due to
Staphylococcus aureus are associated with an increased risk of symptomatic embolism.
 Identifying the causative microorganism is central to diagnosis and appropriate treatment; two
or three blood cultures should routinely be drawn before antibiotic therapy is initiated.
 When infective endocarditis is suspected, echocardiography should be performed as soon as
possible.
 Indications for surgery include heart failure, uncontrolled infection, and prevention of
embolic events.
 Indications for antibiotic prophylaxis have been restricted to invasive dental procedures in
patients with a prosthetic valve, a history of infective endocarditis, or unrepaired cyanotic
congenital heart disease.
THANK U
-
PREDISPOSING
CONDITIONS
CHILDREN(%)
(neonates)
CHILDREN(%)
(2mths-15yr)
ADULTS(%)
(15-60yr)
ADULTS (%)
>60yr
RHD
CHD
MVP
DHD
Parenteral Drug
Abuse
Other
None
MICRBIOLOGY
Streptococci
Enterococci
S. aureus
Coagulase ve
Staphylococci
GNB
Fungi
Polymicrobial
28
72
15-20
50-50
10
10
10
4
2-1
75-90
15-95
2-5
40-50
4
25
5
5
1
25-30
10-20
10-30
RARE
15-35
10-15
25-45
45-65
5-8
30-40
3-5
4-8
1
1
8
2
10
30
10
10
25-40
30-45
15
25-30
5-8
5
RARE
RARE

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IE: CAUSES, SIGNS, DIAGNOSIS AND TREATMENT OF INFECTIVE ENDOCARDITIS

  • 2. Contents of Lecture  Endocarditis – Definitions – Epidemiology – classification – Pathogenesis – Clinical Presentations – Diagnosis – Complications – treatment – prophylaxis
  • 3. DEFINITION  Infective Endocarditis (IE) is a microbial infection of the endocardial (endothelial) surface of the heart.  The vegetation is a variably sized amorphous mass of platelets and fibrin in which abundant micro-organisms and scant inflammatory cells are enmeshed. Braunwald – Heart Disease
  • 4. ENDOCARDITIS Characteristic pathological lesion: vegetation, composed of platelets, fibrin, microorganisms and inflammatory cells.
  • 5. 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%
  • 6. Classification  Acute – Affects normal heart valves – Rapidly destructive – Metastatic foci – Commonly Staph. – If not treated, usually fatal within 6 weeks  Subacute – Often affects damaged heart valves – Indolent nature – If not treated, usually fatal by one year
  • 7. Pathogenesis  ALTERED VALVE SURFACE – Animal experiments suggest that IE is almost impossible to establish unless the valve surface is damaged  DEPOSITION OF PLATELETS AND FIBRIN – nonbacterial thrombotic vegetation (NBTE)  BACTERAEMIA – attaches to platelet-fibrin deposits – Covered by more fibrin – Protected from neutrophils – Division of bacteria – Mature vegetation
  • 8. Pathogenesis  Haemodynamic Factors – Bacterial colonisation more likely to occur around lesions with high degrees of tubulence » eg. small VSD, valvular stenosis – Large surface areas, low flow and low turbulence are less likely to cause IE » eg large VSD,
  • 9.
  • 10. Pathogenesis  Bacteraemia – Transient bacteraemia occurs when a heavily colonised mucosal surface is traumatised » Dental extraction » Periodontal surgery » Tooth brushing » Tonsillectomy » Operations involving the respiratory, GI or GU tract mucosa » Oesophageal dilatation » Biliary tract surgery
  • 11. Site of Infection  Aortic valve more common than mitral  Aortic: – Vegetation usually on ventricular aspect, all 3 cusps usually affected – Perforation or dysfunction of valve – Root abscess  Mitral: – Dysfunction by rupture of chordae tendinae
  • 12. Nonbacterial thrombotic endocarditis Bacteraemia Turbulent blood flow traumatises endothelium Further deposition of fibrin and platelets
  • 13. Clinical Manifestations  Fever, most common symptom, sign  Anorexia, weight-loss, malaise, night sweats  Heart murmur  Petechiae on the skin, conjunctivae, oral mucosa  Splenomegaly  Right-sided endocarditis is not associated with peripheral emboli/phenomena but pulmonary findings predominate
  • 14. CLINICAL MANIFESTATION SYMPTOMS PERCENT SIGNS PERCENT Fever Chills Sweats Anorexia Weight loss Malaise Dyspnea Cough Stroke headache Nausea/vomiting myalgia/arthralgia Chest pain Abdominal pain Back pain confusion 80-95 42-75 25 25-55 25-35 25-40 20-40 25 13-20 15-40 15-20 15-30 8-35 5-15 7-10 10-20 Fever Murmur Changing/new murmur Neurological abnormalities Embolic event Splenomegaly Clubbing Peripheral manifestation Osler’s nodes Splinter hemorrhage Petechiae Janeway’s lesions Retinal lesion 80-90 80-95 10-40 30-40 20-40 15-50 10-20 10-20 7-10 5-15 10-40 6-10 4-10
  • 15. Petechiae—Nonspecific Splinter Hemorrhages Nonspecific Osler’s Nodes--More specific Painful and erythematous nodules Janeway Lesions More specific,Nonpainful
  • 17. Diagnosis: Duke Criteria  In 1994 a group at Duke University standardised criteria for assessing patients with suspected endocarditis  Include -Predisposing Factors -Blood culture isolates or persistence of bacteremia -Echocardiogram findings with other clinical, laboratory findings
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  • 19. Duke Criteria Definite : 2 major criteria : 1 major and 3 minor criteria : 5 minor criteria : pathology/histology findings Possible : 1 major and 1 minor criteria : 3 minor criteria  Rejected : firm alternate diagnosis : resolution of manifestations of IE with 4 days antimicrobial therapy or less
  • 20. Echocardiography  Trans Thoracic Echocardiograpy (TTE) – rapid, non-invasive – excellent specificity (98%) but poor sensitivity – obesity, chronic obstructive pulmonary disease and chest wall deformities  Transesophageal Echo (TOE) – more invasive, sensitivity up to 95%, useful for prosthetic valves and to evaluate myocardial invasion – Negative predictive valve of 92%
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  • 25. Microbiology is very important since virulence of the infecting organism is a significant factor in determining the success rates of both medical and surgical treatment
  • 27. 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 children2  Positive Result – Typical organisms present in at least 2 separate samples
  • 28. Complications  Four etiologies – Embolic – Local spread of infection – Metastatic spread of infection – Formation of immune complexes – glomerulonephritis and arthritis
  • 29. Local Spread of Infection Acute S. aureus IE with perforation of the aortic valve and aortic valve vegetations. Acute S. aureus IE with mitral valve ring abscess extending into myocardium.
  • 30. Principles of Medical Management Sterilization of Vegetations with antibiotics - prolonged Slowly metabolising bacteria due to high density, hence  sensitivity - high dose Bacteria deep inside vegetations -bactericidal
  • 31. Therapy  Streptococci/Enterococci – Determine MIC of Penicillin – Penicillin +/- aminoglycoside – Ceftriaxone alone – Vancomycin +/- aminoglycoside – Cefotaxime/ceftriaxone  HACEK group
  • 32. Therapy  Staphylococci – Native valve » Flucloxacillin +/- aminoglycoside » Vancomycin +/- aminoglycoside/ rifampicin – Prosthetic valve » Flucloxacillin + aminoglycoside + rifampicin » Vancomycin + aminoglycoside + rifampicin
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  • 34. Surgical Therapy  Indications: – Congestive cardiac failure – perivalvular invasive disease – uncontrolled infection despite maximal antimicrobial therapy – Presence of prosthetic valve endocarditis unless late infection – Large vegetation – Major embolus – Heart block
  • 35. Surgical Therapy  The hemodynamic status at the time determines principally operative mortality
  • 36.
  • 37. PROPHYLAXIS  The pathogenesis of infective endocarditis (IE) is presumed to involve the following sequence of events ●Formation of a small thrombus on an abnormal endothelial surface ●Secondary infection of this nidus with bacteria that are transiently circulating in the bloodstream ●Proliferation of bacteria resulting in the formation of vegetations on the endothelial surface  Since the occurrence of bacteremia is crucial to the initiation of an episode of IE, in theory it is reasonable to conclude that preventing or promptly treating transient bacteremia can prevent the above events.
  • 38.  Evidence to support antimicrobial prophylaxis for prevention of endocarditis is weak  antimicrobial prophylaxis for patients with the highest risk medical conditions undergoing procedures likely to result in bacteremia with a microorganism that has the potential ability to cause bacterial endocarditis
  • 39. HIGHEST RISK CONDITIONS  Prosthetic heart valves, including bioprosthetic and homograft valves  A prior history of IE  Unrepaired cyanotic congenital heart disease, including palliative shunts and conduits  Completely repaired congenital heart defects with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first six months after the procedure  Repaired congenital heart disease with residual defects at the site or adjacent to the site of the prosthetic patch or prosthetic device  Valve regurgitation due to a structurally abnormal valve in a transplanted heart
  • 40. HIGHEST RISK PROCEDURES  Dental procedures that involve manipulation of either gingival tissue or the periapical region of teeth or perforation of the oral mucosa; this includes routine dental cleaning.  Procedures of the respiratory tract that involve incision or biopsy of the respiratory mucosa  Gastrointestinal (GI) or genitourinary (GU) procedures in patients with ongoing GI or GU tract infection  Procedures on infected skin, skin structure, or musculoskeletal tissue  Surgery to place prosthetic heart valves or prosthetic intravascular or intracardiac materials
  • 41. Antibiotic Regimens for Prophylaxis of Endocarditis in Adults with High-Risk Cardiac Lesions A. Standard oral regimen  1. Amoxicillin: 2 g PO 1 h before procedure B. Inability to take oral medication  1. Ampicillin: 2 g IV or IM within 1 h before procedure C. Penicillin allergy  1. Clarithromycin or azithromycin: 500 mg PO 1 h before procedure  2. Cephalexinc: 2 g PO 1 h before procedure  3. Clindamycin: 600 mg PO 1 h before procedure D. Penicillin allergy, inability to take oral medication  1. Cefazolinc or ceftriaxonec: 1 g IV or IM 30 min before procedure  2. Clindamycin: 600 mg IV or IM 1 h before procedure
  • 42. key Clinical points  Staphylococci and streptococci account for 80% of cases of infective endocarditis, with staphylococci currently the most common pathogens.  Cerebral complications are the most frequent and most severe extracardiac complications. Vegetations that are large, mobile, or in the mitral position and infective endocarditis due to Staphylococcus aureus are associated with an increased risk of symptomatic embolism.  Identifying the causative microorganism is central to diagnosis and appropriate treatment; two or three blood cultures should routinely be drawn before antibiotic therapy is initiated.  When infective endocarditis is suspected, echocardiography should be performed as soon as possible.  Indications for surgery include heart failure, uncontrolled infection, and prevention of embolic events.  Indications for antibiotic prophylaxis have been restricted to invasive dental procedures in patients with a prosthetic valve, a history of infective endocarditis, or unrepaired cyanotic congenital heart disease.
  • 44. - PREDISPOSING CONDITIONS CHILDREN(%) (neonates) CHILDREN(%) (2mths-15yr) ADULTS(%) (15-60yr) ADULTS (%) >60yr RHD CHD MVP DHD Parenteral Drug Abuse Other None MICRBIOLOGY Streptococci Enterococci S. aureus Coagulase ve Staphylococci GNB Fungi Polymicrobial 28 72 15-20 50-50 10 10 10 4 2-1 75-90 15-95 2-5 40-50 4 25 5 5 1 25-30 10-20 10-30 RARE 15-35 10-15 25-45 45-65 5-8 30-40 3-5 4-8 1 1 8 2 10 30 10 10 25-40 30-45 15 25-30 5-8 5 RARE RARE