INFECTIVE ENDOCARDITIS

an update
Dr.T.V.Rao MD

6/21/2013 Dr.T.V.Rao MD 1
 Beginning of Knowledge on
Endocarditis
• Knowledge about the
origins of endocarditis
stems from the work of
Fernel in the early
1500s, and yet this
infection still presents
physicians with major
diagnostic and
management
dilemmas.

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Definition of Infective Endocarditis
• Infective endocarditis, a serious infection of
the endocardium of the heart, particularly the
heart valves, is associated with a high degree
of illness and death. It generally occurs in
patients with altered and abnormal heart
architecture, in combination with exposure to
bacteria through trauma and other potentially
high-risk activities involving transient
bacteraemia.
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 Definition
Infective Endocarditis (IE): an infection of the
heart’s endocardial surface
Main Classification:
– Native Valve IE
– Prosthetic Valve IE
Additional Consideration
– Intravenous drug abuse (IVDA) IE
– Nosocomial IE
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 Infective Endocarditis
• Febrile illness
• Persistent bacteremia
• Characteristic lesion of microbial infection of
the endothelial surface of the heart
The vegetation
– Variable in size
– Amorphous mass of fibrin & platelets
– Abundant organisms
– Few inflammatory cells
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 Bacterial Endocarditis
Predisposing Factors
1. Dental manipulation
2. Dental disease (caries, abscess)
3. Extra cardiac infection (lung, urinary tract,
4. skin, bone, abscess)
4. Instrumentation (urinary tract, GI tract, IV
infusions)
5. Cardiac surgery
6. Injection drug use
7. None apparent
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 Infective Endocarditis
• Acute
– Toxic presentation
– Progressive valve destruction & metastatic infection developing in
days to weeks
– Most commonly caused by S. aureus

• Sub acute
– Mild toxicity
– Presentation over weeks to months
– Rarely leads to metastatic infection
– Most commonly S. viridans or enterococcus

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 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)

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 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)

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 Causes of Bacteraemia
Brushing teeth alpha-haemolytic
Eating/chewing streptococci from
oral flora
Dental work
Staphylococcus
IV lines (colonised/infected) aureus from
skin/nose
IV drug use

Strep.
Infected site/abscess pneumoniae, S.aureu
s
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 Infecting Organisms
Common bacteria
– Alpha haem streptococci (viridans – S. mitis, S. sanguis) SUBACUTE
– Enterococci (E. faecalis) SUBACUTE
– Coagulase Negative Staphylococci – PROSTHETIC VALVES, SUBACUTE

Less common bacteria

– S. aureus ACUTE
– B-Haemolytic streptococci ACUTE
– Streptococcus pneumonia

Not so common
– Fungi
– Pseudomonas / Coliforms
– HACEK group organisms

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 Bacterial Pathogens
HACEK Group
• Haemophilus spp.
• Actinobacillus
actinomycetemcomitans
• Cardiobacterium hominis
• Eikenella corrodens
• Kingella kingae

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 Infecting Organisms
Streptococci 60-80%
– Alpha-haemolytic Streptococci (viridans – S. mitis, S. oralis) 30-40%
(subacute)
– Enterococci (E. faecalis) 5-18% (subacute)
– Beta-haemolytic streptococci (e.g. Gp A Strep) – rare (acute)

Staphylococci 20-35%
– S. aureus 10-27% (acute)
– Coagulase negative staphylococci (Staph epidermidis) 1-3 %
(mainly prosthetic valve risk, subacute)
Fungi
– Candida – IVDU at risk (usually indolent)
– Aspergillus – rare
Gram-negative bacteria – rare
Culture-negative endocarditis HACEK, Q-fever – cases do occur, subacute

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 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)

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 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

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 Pathophysiology
Turbulent blood flow within the heart - most often
(but not always) – patient has risk factors for this
Turbulent blood flow disrupts valve surface
(endocardium) to produce suitable (sticky) site for
bacterial attachment
Platelet deposition + fibrin may lead to non-bacterial
thrombus or vegetation
Bacteraemia – delivers organisms to the damaged
(sticky) endocardial surface resulting in adherence &
colonisation
Eventual invasion of valve leaflets results in infected
vegetation (sheath of fibrin & platelets, ideal
conditions for further bacterial multiplications,
protection from polymorphs)
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 Infected vs Normal Valve

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 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 vegetation. abscess extending into myocardium.

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 Turbulent Blood Flow
Rheumatic fever history
Old age – calcified valves
Mitral valve prolapse with regurgitation
Prosthetic heart valves
Congenital defects / any structural defect
Cardiac surgery
Central lines
Pacemakers
Intravenous drug abuse
Varying predisposing conditions exist, but in over 50% of cases, no identified valvular lesion
can be found.

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 Distinction between Acute and
Subacute Bacterial Endocarditis

Feature Acute Subacute

Underlying Heart Heart may be normal RHD,CHD, etc.

Disease

Organism S. aureus, Pneumococcus viridans

S. pyogenes, Streptococci,
Enterococcus Entercoccus

Therapy Prompt, vigorous and initiated Can often be delayed

on empirical ground until culture reports and
susceptibilities
available
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 Bacterial Endocarditis
Clinical Features
1. Fever. Antibiotics, salicylates, steroids, severe CHF, uremia may
mask temperature elevations.
2. Murmurs
3. Petechial and cutaneous manifestations. Roth spots Conjunctival
and mucosal petechiae, splinter hemorrhages, Osler nodes and
Janway lesions.
4. Splenomegaly
5. Embolism. Septic or sterile. CNS, spleen, lung, retinal
vessels, coronary artery, large vessels.
6. Renal disease, infarction. Multiple abscesses.
Glomerulonephritis and uremia
7. CHF
8. General. Weight loss, anorexia, debilitation, loss of libido.

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 Symptoms
Acute Sub acute
– High grade fever and – Low grade fever
chills – Anorexia
– SOB – Weight loss
– Arthralgias/ myalgias – Fatigue
– Abdominal pain – Arthralgia's/ myalgia's
– Pleuritic chest pain – Abdominal pain
– Back pain – N/V

The onset of symptoms is usually ~2 weeks or less

from the initiating bacteremia
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 Signs
Fever
Heart murmur
Nonspecific signs – petechiae,
subungal or “splinter” hemorrhages,
clubbing, splenomegaly, neurologic
changes
More specific signs - Osler’s Nodes,
Janeway lesions, and Roth Spots
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 Janeway Lesions

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 Janeway Lesions

1. More specific
2. Erythematous, blanching macules
3. Nonpainful
4. Located on palms and soles
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 Splinter Hemorrhage

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 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
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 Subconjuctival Hemorrhages

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 Septic Retinal Embolus

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 Roth’s Spots

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 Osler’s Nodes

1. More specific
2. Painful and erythematous nodules
3. Located on pulp of fingers and toes
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4. More common in subacute IE
 Bacterial Endocarditis
Laboratory Features
1. Anemia
2. Most commonly elevated WBC
3. ESR elevated, ↓ C′ in patients with
glomerulonephritis
4. Microscopic hematuria
5. Bacteremia. Persistent.≥ 3, ≤ 5 blood cultures.
Aerobic and anaerobic. Different sites.

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 Blood cultures
• Recommendation: Blood cultures remain a
cornerstone of the diagnosis of IE cases and
should be taken prior to starting treatment in
all case
• Meticulous aseptic technique is required
when taking blood cultures, to reduce the risk
of contamination with skin
commensals, which can lead to misdiagnosis.
Guidelines for best practice should be
consulted
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 When to Collect the blood
• In patients with a chronic or sub acute
presentation, three sets of optimally
filled blood cultures should be taken
from peripheral sites with ≥6 h between
them prior to commencing antimicrobial
therapy.
• Taking blood cultures at different times is
critical to identifying a constant
bacteraemia, a hallmark of endocarditis.
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 Timing of blood collection
• In patients with suspected IE and severe
sepsis or septic shock at the time of
presentation, two sets of optimally filled
blood cultures should be taken at
different times within 1 h prior to
commencement of empirical therapy, to
avoid undue delay in commencing
empirical antimicrobial therapy.
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 Start with Empherical Treatment
• It is not always appropriate to withhold
antimicrobial therapy while three sets of
blood cultures are taken over a 12 h
period. This recommendation is intended
to be pragmatic, allowing time to take at
least two sets of blood cultures (the
minimum for a secure microbiological
diagnosis) prior to commencing
antimicrobial therapy.
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 How to collect the Blood
• Sampling of
intravascular lines
should be
avoided, unless part of
paired through-line and
peripheral sampling to
diagnose concurrent
intravascular catheter-
related bloodstream
infection.

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 Longer Incubation is not
Needed
• In the previous BSAC guideline,1 the traditional
recommendation for extended incubation and
terminal subculture was maintained to increase the
yield of fastidious and slow-growing bacteria,
although the evidence for this was tenuous in the era
of automated continuous-monitoring blood culture
systems. In the light of further data and the proven
utility of complementary non-culture-based
technologies, the case for extended incubation and
blind subculture is not justified and therefore it is not
recommended
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 Blood Cultures
Blood Cultures
– Minimum of three blood cultures (ideally spread over 24
hrs)
– Three separate venipuncture sites ideally
– Obtain correct volume of blood for culture bottles
Positive Result
– 1 set gives 90% sensitivity, remaining 2 sets add 8%
– Multiple same cultures are important in confirming
significance, especially for less typical organisms
Negative Result
– Prior antibiotic therapy
– ‘Culture negative endocarditis’ – fastidous orgs / non-
culturable
– May support a non-endocarditis patient diagnosis
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 Blood Cultures
Always need to get full identification
of bacteria from positive blood
cultures in suspected endocarditis
Full sensitivity testing
Need full MIC (minimum inhibitory
concentration) for Penicillin
Liaison with Lab/microbiologist in
cases where endocarditis
suspected/diagnosed
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 Be cautious when you send
multiple samples
• Bacteraemia is
continuous in IE
rather than
intermittent, so
positive results from
only one set out of
several blood
cultures should be
regarded with
caution.
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 Prior administration of Antibiotics give
Negative Culture Results
• Failure to culture a causative microorganism in
IE is often due to the administration of
antimicrobials prior to blood culture, but may
also be due to infection caused by fastidious
or slow-growing microorganisms. Diagnostic
methods should include serological
investigations where they are available and a
systematic approach is advised, based on the
clinical history of the patient and their
exposure to possible risk factors.
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 Culture Negative Results may yield
..less known microbes
• Microorganisms
that should be
considered first
include Coxiella
burnetii (Q
fever) and
Bartonella spp.
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 Additional Tests
CBC
ESR and CRP
Complement levels (C3, C4, CH50)
RF
Urinalysis
Baseline chemistries

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 Imaging
Chest x-ray
– Look for multiple focal infiltrates and calcification
of heart valves
ECG
– Rarely diagnostic
– Look for evidence of ischemia, conduction delay,
and arrhythmias
Echocardiography
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 Indications for Echocardiography
Transthoracic echocardiography (TTE)
– First line if suspected IE
– Native valves
Trans esophageal echocardiography (TEE)
– Prosthetic valves
– Intracardiac complications
– Inadequate TTE
– Fungal or S. aureus or bacteremia
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 Making the Diagnosis
Pelletier and Petersdorf criteria (1977)
– Classification scheme of definite, probable, and possible IE
– Reasonably specific but lacked sensitivity

Von Reyn criteria (1981)

– Added “rejected” as a category
– Added more clinical criteria
– Improved specificity and clinical utility

Duke criteria (1994)

– Included the role of echocardiography in diagnosis
– Added IVDA as a “predisposing heart condition”

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 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

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 Bacterial Endocarditis
Therapy and Prophylaxis
1. Prolonged; high dosages; use of bactericidal
drugs
2. Serum antibiotic levels and MBC of the
organism
3. Viridans streptococci, Enterococcus, S.
aureus, S. pneumoniae, S. pyogenes
4. Institution of therapy on empirical grounds
5. Proven negative blood cultures on Abx
6. Prophylaxis: dental extraction, GU.
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 Treatment
Parenteral (IV) antibiotics
– High serum concentrations to penetrate
vegetation's
– Prolonged treatment to kill dormant
bacteria clustered in vegetation's
Surgery
– Intracardiac complications/paravalve
abscess
Surveillance blood cultures
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 Treatment - Specific
Modify empiric therapy once
cultures/sensitivities known
Long duration 4-6 weeks Rx is required
Refer to Trust Guidelines / BSAC Working Party
Guidelines (2004)
Liaise with Microbiologist
Liaise with Cardiac Surgeon if needed
Monitor response to treatment
(clinical, CRP, ECHO) & look for complications

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 Complications
Four etiologies
–Embolic
–Local spread of infection
–Metastatic spread of infection
–Formation of immune complexes –
glomerulonephritis and arthritis

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 Embolic Complications
Occur in up to 40% of patients with IE
Predictors of embolization
– Size of vegetation
– Left-sided vegetation's
– Fungal pathogens, S. aureus, and Strep.
Bovis
Incidence decreases significantly after
initiation of effective antibiotics
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 Embolic Complications
Stroke
Myocardial Infarction
– Fragments of valvular vegetation or vegetation-
induced stenosis of coronary ostia
Ischemic limbs
Hypoxia from pulmonary emboli
Abdominal pain (splenic or renal infarction)

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 Metastatic Spread of Infection
Meningitis and/or encephalitis
Vertebral osteomyelitis
Metastatic abscess
–Kidneys, spleen, brain, soft
tissues
Septic arthritis
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 Prevention – the procedure
• Dental procedures
known to produce
bleeding
• Tonsillectomy
• Surgery involving GI,
respiratory mucosa
• Esophageal dilation
• ERCP for obstruction
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• Gallbladder surgery
• Cystoscopy, urethral
dilation
• Urethral catheter if
infection present
• Urinary tract
surgery, including
prostate
• I&D of infected tissue
57
 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
–ID CONSULT EVERY TIME
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 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 micro vascular complications/major
emboli
• Intracardiac/extra cardiac septic complications
• Drug reaction

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 Prevention
• Prophylactic regimen targeted against
likely organism
– Strep. viridans – oral, respiratory,
esophageal
– Enterococcus – genitourinary,
gastrointestinal
– S. aureus – infected skin, mucosal surfaces
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Prevention – the underlying lesion
• High risk lesions • Intermediate risk
– Prosthetic valves – MVP with murmur
– Prior IE
– Pure MS
– Cyanotic congenital heart disease
– Tricuspid disease
– PDA
– Pulmonary stenosis
– AR, AS, MR,MS with MR
– VSD – ASH
– Coarctation – Bicuspid Ao valve with no
– Surgical systemic-pulmonary hemodynamic significance
shunts

Lesions at highest risk

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 Current Trends
Uncommon bacteria a concern
• Endocarditis has been documented for
approximately 450 years, the diagnostic challenges
and treatment dilemmas are as real today as they
were in the time of Fernel . Major advances have
been made in the diagnosis of endocarditis, in both
laboratory and clinical (imaging) parameters, but we
are witnessing the emergence of several newly
described causal bacterial species, such as
Tropheryma whippelii and Bartonella spp., as well as
sporadic case reports of unusual and uncommon
causal organisms, including Finegoldia sp., Gemella
spp., and Abiotrophia defective.
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 Molecular Methods
• In addition, since diagnostic methods, mainly
16S rDNA polymerase chain reaction (PCR) and
sequencing, are now beginning to identify such
infections, no evidence base exists to help determine
effective antimicrobial drug regimens to successfully
treat endocarditis caused by such organisms.
Furthermore, as specimens from many of these
infections are culture-negative, conventional
antibiotic susceptibility testing does not help the
cardiologist decide on the most suitable
antimicrobial drug regimens.
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 New challenges in Endocarditis
• 1) the emergence of antimicrobial resistance in classic
infective endocarditis microflora, namely, the gram-
positive cocci; 2) the existence of antimicrobial
resistance in complex ecologic biofilms; 3) the changing
pattern of causal agents now regarded as important
pathogens of infective endocarditis, e.g., Bartonella
spp., T. whippelii, and fungi; and 4) changing
epidemiologic trends of persons who acquire infective
endocarditis, including injection drug users, persons
with HIV/AIDS, children with congenital heart
defects, and persons undergoing body piercing.

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 References
• Emerging Issues in Infective Endocarditis
Beverley C. Millar* and John E. Moore
• Guidelines for the diagnosis and
antibiotic treatment of endocarditis in
adults: a report of the Working Party of
the British Society for Antimicrobial
Chemotherapy F. Kate Gould etal

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 • The Programme created by
Dr.T.V.Rao MD for Medical
Professionals in the Developing
World
• Email
• doctortvrao@gmail.com

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