Infective Endocarditis

Dr Rajesh Padhi,
M.D.,DipCard,FCCP
 Infective Endocarditis
Essential Pathophysiology
characteristics
General definitions Clinical features
and epidemiology
– NVE
Treatment
– I.V. drug abuse
– PVE
Pathogenesis
 Infective Endocarditis
DEF: Infectious endocarditis (IE) denotes infection of the
endocardial surface of the heart and implies the physical
presence of microorganisms in the lesion.
MC involves heart valves (either native or prosthetic)
Also lower pressure side in VSD, mural enocardium, on
intracardiac devices
The prototypic lesion of infective endocarditis, the vegetation is
a mass of platelets, fibrin, microcolonies of microorganisms, and
scant inflammatory cells.

– Variable in size
–
the vegetation
Amorphous mass of fibrin & platelets
– Abundant organisms
– Few inflammatory cells
 Important Definitions
Endarteritis - Inflammation of the intima of an artery.
Janeway lesion - Erythematous, nontender lesions on
fingers, palm, or sole.
Mycotic aneurysms - Aneurysmal dilatation of a vessel
caused by invasion of the vascular wall from infective
endocarditis.
Osler nodes - Small, tender, purple erythematous
subcutaneous nodules visibly found on the pulp of digits.
Roth spots - Retinal hemorrhages with a clear center.
Splinter hemorrhage - An embolic subungual hemorrhage
located proximally in the nail bed.
Vegetations - Growth consisting of fused platelets, fibrin,
and other bacteria adherent to a heart valve or other
vascular structure.
 Definition of IE According to the
Modified Duke Criteria
Major criteria  1
Blood culture positive for IE 
Typical microorganisms consistent with IE from two
separate blood cultures:       Viridans streptococci,
Streptococcus bovis, HACEK group, Staphylococcus
aureus; or        Community-acquired enterococci in the
absence of a primary focus; or    
Microorganisms consistent with IE from persistently
positive blood cultures, defined as follows:       At least
two positive cultures of blood samples drawn more than
12 h apart; or       All of three or a majority of greater than
four separate cultures of blood (with first and last sample
drawn at least 1 h apart)    
Single positive blood culture for Coxiella burnetti or
antiphase 1 IgG antibody titer greater than 1:800 
 Definition of IE According to the
Modified Duke Criteria contd..
Major Criteria 2
Evidence of endocardial involvement
Echocardiogram positive for IE (TEE recommended in
patients with prosthetic valves, rated at least "possible IE"
by clinical criteria, or complicated IE [paravalvular
abscess]; TTE as first test in other patients), defined as
follows:    
Oscillating intracardiac mass on valve or supporting
structures, in the path of regurgitant jets, or on implanted
material in the absence of an alternative anatomic
explanation; or       Abscess; or       
New partial dehiscence of prosthetic valve  
New valvular regurgitation (worsening or changing of
preexisting murmur not sufficient)
 Definition of IE According to the
Modified Duke Criteria contd..
Minor criteria 
1. Predisposition, predisposing heart condition, or injection
drug use  
2. Fever, temperature greater than 100.4°F (38°C)  
3. Vascular phenomena, major arterial emboli, septic
pulmonary infarcts, mycotic aneurysm, intracranial
hemorrhage, conjunctival hemorrhages, and Janeway
lesions  
4. Immunologic phenomena; glomerulonephritis, Osler
nodes, Roth spots, and rheumatoid factor  
5. Microbiologic evidence: positive blood culture but does not
meet a major criterion,a or serologic evidence of active
infection with organism consistent with IE
6. Echocardiographic minor criteria eliminated
 Definition of IE According to the
Modified Duke Criteria contd..
Definite infective endocarditis
   Pathologic criteria 
1. Microorganisms demonstrated by culture or
histologic examination of a vegetation, a
vegetation that has embolized, or an
intracardiac abscess specimen; or    
2. 2. Pathologic lesions; vegetation, or
intracardiac abscess confirmed by histologic
examination showing active endocarditis
 Definition of IE According to the
Modified Duke Criteria contd..
Definite infective endocarditis
Clinical criteria     
1. Two major criteria; or    
2. One major criterion and three minor
criteria; or    
3. Five minor criteria
 Definition of IE According to the
Modified Duke Criteria contd..
Possible infective endocarditis 
1. One major criterion and one minor criterion; or  
2. Three minor criteria
Rejected     
1. Firm alternate diagnosis explaining evidence of infective
endocarditis; or    
2. Resolution of infective endocarditis syndrome with
antibiotic therapy for less than 4 days; or    
3. No pathologic evidence of infective endocarditis at
surgery or autopsy, with antibiotic therapy for less than 4
days; or    
4. Does not meet criteria for possible infective endocarditis,
as noted above
 Classification:
1-Acute:
- Aggressive.
- Virulent organisms such as Staph. Aureus.
- Often affects the normal valves.
2- Subacute:
- Indolent course over weeks to months.
- Less virulent organisms such as Strep. Viridans.
- Usually develops on abnormal valves.
3- Early Prosthetic Valve Endocarditis (EPVE):
- Infection of the artificial valves within 2 months after
surgery.
4- Late Prosthetic Valve Endocarditis (LPVE):
-Infection of the artificial valves > 2 months after
surgery.
5- Non - Bacterial Thrombotic Endocarditis (NBTE).
- Any endocardial sterile vegetations – wide spectrum.
 Etiology:
 NBTE:
- Endothelial damage leads to platelet aggregation and deposition
with Fibrin and development of sterile vegetations.
 ABE/SBE:
- Microbes probably colonize the pre-existing NBTE or even invade
endothelium in the case of ABE.
 MV > AV >TV >PV.
 Drug Abusers:
- TV, MV, AV, PV.
 Infection of vegetations → Friability and Embolic
Phenomena.
 Immunological Phenomena.
 Causative organisms:
1- ABE:
- Staph. AUreus. - Hemophilus Influenza.
- Strep. Pneumonia. - enterococcal Species.
2- SBE:
- Strep. Viridans. - Strep. Bovis.
- Enterococcal Species. - HACEK group.
3- EPVE:
- Staph. Epidermedis.(CONS) - Staph. aureus.
- Asperigillus Species. - Gram -ve. Rods (E-Coli, Pseudomonas).
4- LPVE:
- St. Viridans. Staph. aureus - Enterococci (S. Bovis & Fecalis).
5- Drug Abusers:
- Staph. Aureus. - Candidiasis.
- Pseudomonas & E-coli. Left sided - Enterococci.
 Risk Factors:
1- High Risk:
- Prosthetic Heart Valves.
- Previous Endocarditis.
- Congenital cyanotic heart disease.
- MR.
- AR.
- VSD.
- PDA.
- Coarctation of the Aorta.
 Risk Factors:contd..
2- Intermediate Risk:
- MVP with mild MR.
- Pure MS.
- TVD.
- PVD.
- HOCM (IHSS).
- AS.
- Non-Valvular prosthetic cardiac implants.
- Intracardiac catheters.
3- Low Risk:
- ASD ( Ostium secundum Type).
- MVP without MR.
4- Other Risk Factors:
- IV. Drug abuse.
- AV shunts for hemodialysis.
- Massive Wounds such as burns.
 CLINICAL PICTURE:
- Fever: → Low grade in SBE.
→ High grade in ABE.
- Pallor: → Anemia.
- chills, rigors and sweating.
- Malaise and anorexia.
- New murmurs or increasing the grade of an old murmurs.
- Murmurs may be absent in severe cases.
- Focal neurological signs ( embolic phenomena or meningitis ).
- Delerium and headache.
- Chest pain, dyspnea, cough and hemoptysis.
 CLINICAL PICTURE (cont’d):
- Flank pain, hematuria, left upper quadrant pain → evidence of
distal emboli or Immune Complex Glomerulo- Nephritis.
- Cold painful extremity.
- Splenomegaly.
- Peticheal hemorrhage.
- Osler’s nodules.
- Splinter Hge.
- Janeway lesions.
- Finger clubbing.
- Roth’s Spots in the retina.
- Conjunctival hemorrhage.
- Rales and gallop.
INFECTIVE ENDOCARDITIS
INFECTIVE ENDOCARDITIS
INFECTIVE ENDOCARDITIS
INFECTIVE ENDOCARDITIS
 Infective Endocarditis
Typically involves the valves
– May involve all structures of the heart
Chordae tendinae
Sites of shunting
Mural lesions
– Infection of vascular shunts, by strict definition, is
endarteritis, but lesion is the same
Majority of cases caused by streptococcus,
staphylococcus, enterococcus, or fastidious
gram negative cocco-bacillary forms
 Infective Endocarditis
Gram negative organisms
– P. aeruginosa most common
– HACEK - slow growing, fastidious organisms
that may need 3 weeks to grow out of culture
Haemophilus sp.
Actinobacillus
Cardiobacterium
Eikenella
Kingella
 Infective Endocarditis
Acute
– Toxic presentation
– Progressive valve destruction & metastatic infection
developing in days to weeks
– Most commonly caused by S. aureus
Subacute
– Mild toxicity
– Presentation over weeks to months
– Rarely leads to metastatic infection
– Most commonly S. viridans or enterococcus
 Infective Endocarditis
Case rate may vary between 2-3 cases /100,000
to as high as 15-30/100,000 depending on
incidence of i.v. drug abuse and age of the
population
– 55-75% of patients with native valve endocarditis
(NVE) have underlying valve abnormalities
MVP
Rheumatic
Congenital
ASH or:
i.v. drug abuse
 Infective Endocarditis
Case rates
– 7-25% of cases involve prosthetic valves
– 25-45% of cases predisposing condition can
not be identified
 Infective Endocarditis
Pediatric population
– The vast majority (75-90%) of cases after the
neonatal period are associated with an underlying
congenital abnormality
Aortic valve
VSD
Tetralogy of Fallot
– Risk of post-op infection in children with IE is 50%
Microbiology
– Neonates: S. aureus, coag – staph, group B strep
– Older children: 40% strep, S. aureus
 Infective Endocarditis
Adult population
– MVP – prominent predisposing factor
High prevalence in population
– 2-4%
– 20% in young women
Accounts for 7 – 30% NVE in cases not related to drug
abuse or nosocomial infection
– Relative risk in MVP ~3.5 – 8.2, largely confined to
patients with murmur, but also increased in men and
patients >45 years old
MVP with murmur – incidence IE 52/100/000 pt. years
MVP w/o murmur – incidence IE 4.6/100,000 pt. years
 Infective Endocarditis
Adult population
– Rheumatic Heart Disease
20 – 25% of cases of IE in 1970’s & 80’s
7 – 18% of cases in recent reported series
Mitral site more common in women
Aortic site more common in men
– Congenital Heart Disease
10 – 20% of cases in young adults
8% of cases in older adults
PDA, VSD, bicuspid aortic valve (esp. in men>60)
 Infective Endocarditis
Intravenous Drug Abuse
– Risk is 2 – 5% per pt./year
– Tendency to involve right-sided valves
Distribution in clinical series
– 46 – 78% tricuspid
– 24 – 32% mitral
– 8 – 19% aortic
– Underlying valve normal in 75 – 93%
– S. aureus predominant organism (>50%, 60-
70% of tricuspid cases)
 Infective Endocarditis
Intravenous Drug Abuse
– Increased frequency of gram negative
infection such as P. aeruginosa & fungal
infections
– High concordance of HIV positivity & IE (27-
73%)
HIV status does not in itself modify clinical picture
Survival is decreased if CD4 count < 200/mm3
 Infective Endocarditis
Prosthetic Valve Endocarditis (PVE)
– 10 – 30% of all cases in developed nations
– Cumulative incidence
1.4 – 3.1% at 12 months
3.2 – 5.7% at 5 years
– Early PVE – within 60 days
Nosocomial (s. epi predominates)
– Late PVE – after 60 days
Community (same organisms as NVE)
 Infective Endocarditis
Pathology
– NVE infection is largely confined to leaflets
– PVE infection commonly extends beyond
valve ring into annulus/periannular tissue
Ring abscesses
Septal abscesses
Fistulae
Prosthetic dehiscence
– Invasive infection more common in aortic
position and if onset is early
 Infective Endocarditis
Pathogenesis

Endothelial damage

Platelet-fibrin thrombi

Microorganism adherence
 Infective Endocarditis
Nonbacterial Thrombotic Endocarditis
Endothelial injury
Platelet-fibrin thrombi
Hypercoagulable state
– Lesions seen at coaptation points of valves
Atrial surface mitral/tricuspid
Ventricular surface aortic/pulmonic
Modes of endothelial injury
High velocity jet
Flow from high pressure to low pressure chamber
Flow across narrow orifice of high velocity
– Bacteria deposited on edges of low pressure sink or
site of jet impaction
Venturi Effect
Venturi Effect
 Conversion of NBTE to IE
Frequency & magnitude of bacteremia
Density of colonizing bacteria
Oral > GU > GI
Disease state of surface
Infected surface > colonized surface
Extent of trauma
Resistance of organism to host defenses
Most aerobic gram negatives susceptible to complement-
mediated bactericidal effect of serum
Tendency to adhere to endothelium
Dextran producing strep
Fibronectin receptors on staph, enterococcus, strep,
Candida
 Pathophysiology
Clinical manifestations
– Direct
Constitutional symptoms of infection (cytokine)
– Indirect
Local destructive effects of infection
Embolization – septic or bland
Hematogenous seeding of infection
N.B. may present as local infection or persistent
fever, metastatic abscesses may be small, miliary
Immune response
Immune complex or complement-mediated
 Pathophysiology
Local destructive effects
Valvular distortion/destruction
Chordal rupture
Perforation/fistula formation
Paravalvular abscess
Conduction abnormalities
Purulent pericarditis
Functional valve obstruction
 Pathophysiology
Embolization
Clinically evident 11 – 43% of patients
Pathologically present 45 – 65%
High risk for embolization
Large > 10 mm vegetation
Hypermobile vegetation
Mitral vegetations (esp. anterior leaflet)
Pulmonary (septic) – 65 – 75% of i.v. drug abusers
with tricuspid IE
 Clinical Features
Interval between index bacteremia & onset
of sx’s usually < 2 weeks
May be substantially longer in early PVE
Fever most common sign
May be absent in elderly/debilitated pt.
Murmur present in 80 – 85%
Generally indication of underlying lesion
Frequently absent in tricuspid IE
Changing murmur
 Classical Peripheral
Manifestations

Less common today

Not seen in tricuspid endocarditis

Petechiae most common

Janeway Lesions
Splinter Hemorrhage
Osler’s Nodes
Subconjunctival Hemorrhages
Roth’s Spots
 Clinical Features
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
 Diagnosis
Published criteria for diagnostic purposes
in obscure cases
High index of suspicion in patients with
predisposing anatomy or behavior
Blood cultures
Echocardiography
– TTE – 60% sensitivity
– TEE – 80 – 95% sensitive
 Goals of Therapy
1. Eradicate infection

2. Definitively treat sequelae of destructive

intra-cardiac and extra-cardiac lesions
 Antibiotic Therapy
Treatment tailored to etiologic agent
– Important to note MIC/MBC relationship for
each causative organism and the antibiotic
used
– High serum concentration necessary to
penetrate avascular vegetation
 Antibiotic Therapy
Treatment before blood cultures turn
positive
Suspected ABE
Hemodynamic instability
– Neither appropriate nor necessary in patient
with suspected SBE who is hemodynamically
stable
 Antibiotic Therapy
Effective antimicrobial treatment should
lead to defervescence within 7 – 10 days
– Persistent fever in:
IE due to staph, pseudomonas, culture negative
IE with microvascular complications/major emboli
Intracardiac/extracardiac septic complications
Drug reaction
 Surgical Treatment of Intra-
Cardiac Complications
NYHA Class III/IV CHF due to valve
dysfunction
– Surgical mortality – 20-40%
– Medical mortality – 50-90%
Unstable prosthetic valve
– Surgical mortality – 15-55%
– Medical mortality – near 100% at 6 months
Uncontrolled infection
 Surgical Treatment of Intra-
Cardiac Complications
Unavailable effective antimicrobial therapy
– Fungal endocarditis
– Brucella
S. aureus PVE with any intra-cardiac
complication
Relapse of PVE after optimal therapy
 Surgical Treatment of Intra-
Cardiac Complications
Relative indications
– Perivalvular extension of infection
– Poorly responsive S. aureus NVE
– Relapse of NVE
– Culture negative NVE/PVE with persistent
fever (> 10 days)
– Large (> 10mm) or hypermobile vegetation
– Endocarditis due to highly resistant
enterococcus
 Prevention

Prophylactic regimen targeted against

likely organism
– Strep. viridans – oral, respiratory, eosphogeal
– Enterococcus – genitourinary, gastrointestinal
– S. aureus – infected skin, mucosal surfaces
 Prevention – the procedure
Dental procedures Gallbladder surgery
known to produce Cystoscopy, urethral
bleeding dilation
Tonsillectomy Urethral catheter if
Surgery involving GI, infection present
respiratory mucosa Urinary tract surgery,
Esophageal dilation including prostate
ERCP for obstruction I&D of infected tissue
Prevention – the underlying lesion
High risk lesions
– Prosthetic valves
– Prior IE
– Cyanotic congenital heart
disease
– PDA
– AR, AS, MR,MS with MR
– VSD
– Coarctation
– Surgical systemic-
pulmonary shunts
Lesions at highest risk
Intermediate risk
– MVP with murmur
– Pure MS
– Tricuspid disease
– Pulmonary stenosis
– ASH
– Bicuspid Ao valve with no
hemodynamic significance
Prevention – the underlying lesion

Low/no risk
– MVP without murmur
– Trivial valvular regurg.
– Isolated ASD
– Implanted device
(pacer, ICD)
– CAD
– CABG
This wallet card is to be given to patients by their physician. Healthcare professionals,
please see back of card for reference to the complete statement.

Name: ____________________________________________
needs protection from
BACTERIAL ENDOCARDITIS
because of an existing
HEART CONDITION
Diagnosis: __________________________________________
Prescribed by: _______________________________________
Date: ______________________________________________
 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