Infective Endocarditis

C.Thoms-Rodriguez
 Introduction
A microbial infection of the endocardial surface
of the heart
Most commonly heart valves but may also occur
at other sites (the site of a septal defect, on the
chordae tendineae or on the mural
endocardium)
Characteristic lesion is a vegetation composed
of platelets, fibrin, microorganisms &
inflammatory cells
Vegetation on Valve
 History
1723: Lazzaire Riviere first described
gross autopsy findings
1885: Wiliam Osler presented the 1st
comprehensive description in English
1966: Lerner & Weinstein published a
landmark series of articles in NEJM on
Infective Endocarditis in the Antibiotic Era
 Incidence & Classification
Incidence is 2-4 cases per 100,000
persons per year

Native valve endocarditis (NVE): acute/

subacute

Prosthetic valve endocarditis (PVE) (up to

25% of cases of IE): Early: <60dys after
implant. Late: >60 dys
 Infective Endocarditis
May be acute or subacute chronic
depending on the severity and progression
of disease
Acute: often involves normal valves (Staph
aureus & Gp B Strep)
Subacute: often affects abnormal valves
The infection causes valvular insufficiency
which can lead to CCF & abscesses in the
myocardium (S viridans & Enterococcus)
Fatal if untreated
 Classification contd.
NIE/ HCIE: Nosocomial: manifests within 48hrs
after hospitalization or procedure done within 4
wks of onset. (May be longer with PVE)
May occur in valve damaged by placement of a
catheter or in a previously damaged valve. (S.
aureus is commonest then Enterococcus from
GU)
One study: 7-29% IE were NIE with 50% due to
intravascular devices
Other sources: GIT or GU procedures or surgical
wound infection
(IVDA) IE : Intravenous drug abuse
 Epidemiology
Changing because of increased longevity,
new predisposing factors & increase in
HAI
Increased longevity: degenerative valvular
disease, prosthetic valves, increased
exposure to nosocomial bacteremia
May occur in any age. Median age has
increased from 3040 to 47- 69yrs. 25-
50% of cases occurring in >60yrs
Where IE is caused by IVDA, pts are
younger
 Epidemiology
No racial predilection
3 times as common in males as females
Associated with: Poor dental hygiene
Long term hemodialysis
Diabetes mellitus
HIV
Poor Dental Hygiene?
 Underlying Valvular pathology
Where there is valvular pathology (changes have
occurred):
Rheumatic heart disease:<20% cases
Calcific aortic stenosis: 50% elderly pts have this
underlying cause.
Congenital heart disease: 15%
Includes: PDA, VSD, MVP (young adults)
Valvular damage caused by previous IE
PVE: up to 25% of IE (mitral> aortic)
With IVDA IE 75% have no underlying valvular
abnormality
 Organisms
Commonest cause overall: Staphylococcus
aureus (>50% not assoc. with valve disease)
Strep viridans: commonest cause of subacute.
Includes: Streptococcus sanguis, S mutans, S
mitis, S. intermedius gp
S bovis (Gp D Strep)
(S. bovis common in elderly & assoc. with pre-
existing colonic lesions)
Enterococcus: 3rd most common cause of IE
 Organisms contd.
Gp B Strep: pregnant pts & older pts DM, Ca etc
Gp A,C,G Strep: Resembles Staph aureus IE
CNS: Common path. in early PVE occasionally
in NVE eg Staph. lugdunensis associated with
valve destruction
Pseudomonas aeruginosa: usually acute
HACEK organisms: Haemophilus aphrophilus,
Actinobacillus actinomycetemcomitans,
Cardiobacterium hominis, Eikenella corrodens,
Kingella kingae: most common Gm neg. orgs.
Usually cause subacute infections
 Organisms contd.
Tropheryma whippelliPolymicrobial IE:
usually IVDA
(uncommon)
Commonest combination is Pseudomonas
& Enterococci
Fungi: subacute disease
Candida albicans is commonest for
NVE & PVE
 Used to be Culture Negative
The newer systems available recover most
pathogens in 4-5 days:
Identified with newer systems :
HACEK group
Nutritionally variant Streptococcus
Serology: Coxiella, Brucella,Legionella
& Chlamydia spp
Molecular: PCR
Current Causes of Culture Negative IE
Previous use of antibiotics is commonest
cause
Bartonella spp
Coxiella burnetti spp
Legionella, Chlamydia, Brucella
Fungi eg Candida spp
Staph aureus if burrowed deep within
thrombus leaving surface sterile
IE remains diagnostic & therapeutic
challenge
 Pathophysiology
Bacteremia results in delivery of organism
to valve surface
Bacteremia may be secondary to dental
extraction, gingivitis, brushing teeth, GU
surgery, abdominal surgery etc.
Most bacteremias are transient & are
removed from by host defenses
 Pathophysiology contd.
Next step is adherence
Colonization of valves by microbes is complex
Once microbes establish themselves on the
surface, platelet aggregation & fibrin deposition
accelerate at the site
Bacteria multiply, are protected from host
defenses by thick layers of platelets & thrombin
Organisms deep within the vegetation hibernate
because of scarcity of nutrients & are less
susceptible to antimicrobials that act on cell wall
Invasion of the valve leaflets results in the
problems
Pathophysiology
 Clinical Features
Varies with type of IE
Acute IE: Aggressive
Subacute IE: Indolent
 Clinical: Acute IE
Acute onset of high grade fever >38C
Chills
Fatigue
Rapid destruction of valves
Murmur
Rapid onset of CCF
Complications result from intracardiac
disease & metastatic infection produced
by emboli
 Complications of Acute IE
Aneurysms
Valvular insufficiency
Intraventricular abscesses
Myocardial abscesses
Pericarditis
Multiple abscesses can occur in every
organ where emboli are deposited
Immunological phenomena do not occur
because of the shortened course
Clinical Features of Subacute IE
Indolent process:
Fever
Fatigue
Anorexia
Night sweats
Weight loss
Flulike syndrome
Murmur
 Subacute: Clinical
Extracardiac manifestations are the result of
arterial embolisation of fragments of
vegetation:
CVA
Blindness: retinal artery
Coronary artery emboli: MI
 Clinical: Sub-acute IE contd.
Persistent bacteremia stimulate immune
system: circulating immune complexes:
Petechiae: hands,feet,chest,abd
Subungual (splinter) haemorrhages
Oslers nodes: painful nodes on hands &
feet
Back pain: IC in disk spaces
Clubbing (more common in untreated)
Roth spots: retinal haem. with pale centres
Janeway lesions: painless macules on
hands & feet: infectious vasculitis: arise
from infected micro-emboli.
Late Petechial Rash: Red, non-
blanching
Splinter Haemorrhage
Oslers Nodes: painful
Clubbing
Roth Spots
Janeway lesions: painless macules
 Clinical: PVE, NIE
Clinical features of PVE resemble NVE
CCF occurs earlier & is more severe

NIE(48hrs -4wks for NVE): Acute onset

Signs of endocarditis uncommon
Persistent bacteremia eg 72 hrs or more
after removal of infected catheter
Sepsis syndrome: hypotension, fever,
leukocytosis, organ failure
 Lab Diagnosis
Culture: Blood, valvular material, embolic
tissue
Serological tests
Molecular based techniques: Blood,
valvular lesions, isolates from culture
ID, resistance genes
Blood Culture/ BacT Alert bottles
Aseptic precautions
Disinfect tops of
bottles with alcohol/
Betadine before
inoculating them
Do not re-palpate the
vein after cleaning
Use appropriate skin
disinfectants
Clean centrifugally
Skin contaminants
can confuse the
results
Bactec Bottles/ BacT Alert

8-10 mls per bottle

Aerobic & anaerobic
or 2 aerobic bottles
Do not cover bar
code
Take to lab
immediately or
leave at room temp.
Bactec Machine: automated
 Lab Diagnosis contd.
3-5 sets of blood cultures (BC)
Draw sample from different sites (within 2 hrs) if acute
IE, before antibiotic therapy
(Never draw only one set: one is worse than none!!)
For subacute IE draw 3-5 sets over 24 hrs (detects up to
98% if no AB)
Continuous bacteremia based on blood culture results
(>30 mins)

When BC negative after blood is drawn 48hrs after

antibiotic therapy stopped, the 2nd set should be drawn 7
days later. If these are negative reconsider diagnosis of
IE
 Cultures contd.
In lab, used to keep IE BCs for up to 6
weeks for fastidious organisms
Now >5 days is unnecessary for the
detection of HACEK & other fastidious
bacteria with modern automated systems
Antimicrobial Sensitivity Testing
 Diagnosis: Modified Duke
Criteria
Major criteria:
A) Blood culture:
Positive blood cultures (>2/2) with typical
IE organisms eg Staph & Enterococcus)
Persistently positive BCs
Single positive culture for C burnetii
B) Positive echo for IE
 Modified Duke Criteria contd.
Minor Criteria:
Predisposing cardiac cond: RHD,PV, IE
Fever (>38C/100.4F)
Immunologic phenomena: Oslers nodes
Vascular phenomena
Microbiological evidence:
a)Positive BCs but not meeting major crit.
b) Serological evidence of active infection
 Modified Duke Criteria contd.
A) Definite:
Microorganisms demonstrated by culture
or histology of vegetation or emboli OR
Intracardiac abscess specimen
OR
2 major criteria OR
one major & 3 minor criteria OR
5 minor criteria
 Modified Duke Criteria contd.
B) Possible:
One major & one minor; OR
3 minor criteria

C) Rejected:
Firm alternative diagnosis; OR
Resolution after days antimicrobials
 Treatment
In acute IE: Start treatment ASAP
Obtain 3-5 sets within 90 120 mins
Start empirical antibiotic coverage
In sub-acute IE: Treatment may be delayed
until C/S ready
Treatment will vary with agent
Eradication of organisms is difficult
IV Bactericidal antibiotics preferred
Duration: long
 Treatment contd.
Pathogen NVE treatment
Strep viridans Pen G or CRO:4wks
Strep bovis PenG + GM

Enterococcus spp Pen G +GM: 6 wks

MSSA Clox: 4-6wks +/- GM3-5/7
MRSA Va+/- GM initially
HACEK CRO for 4 wks or AMP +
GM 4 wks
 Treatment
Pathogen PVE
Strep viridans Pen G 6wks +GM 2wks
Strep bovis As above
Enterococcus PenG 6wk +GM 6 wks
MSSA Clox+Rif 6wks &GM2wk
MRSA Va + Rif 6wks +
GM 2wks
HACEK CRO 6wks or
AMP + GM 6wks
 Antibiotic Prophylaxis
For dental procedures: No longer routine
Of the total no of cases yearly, very small
no. from dental procedures. Only a small
no. would be prevented by AB
Random bacteremia from routine acts eg
brush/ floss/ chewing (5-6M times risk!)
Emphasis should be on dental care esp in
pts with high risk cardiac conditions eg
PV, previous IE, some CHD
 Prophylaxis
Antibiotic prophylaxis for dental procedures
recommended for :
Prosthetic cardiac valve
Previous IE
Some Congenital heart Diseases
 Prophylaxis Regimens
Amoxil, Ampicillin : 2gms, 1 hr before OR
Ceftriaxone: 1gm IM/IV

Allergy to Pen:
Cephalexin: 2g OR
Clindamycin: 600mg OR
Ceftriaxone: 1gm OR
Azithro or Clarithromycin 500mg
 THE END
Acknowledgements: AM
Nicholson for her contribution
of slides