INFECTIVE ENDOCARDITIS .

DEFINITION
•An infection of the endocardial lining of the heart that includes
heart valves, mural endocardium, and endocardial covering of the
implanted material such as prosthetic valves and intracardiac
devices.
•acute or subacute
•Staphylococcus aureus and other pyogenic bacteria, such as
Streptococcus pneumoniae or β-hemolytic streptococci - virulent or
acute clinical illness.
•Low-virulence organisms such as a-hemolytic streptococci,
enterococci, or coagulase-negative staphylococci - subacute form.
 EPIDEMIOLOGY
•Between 1986 and 1995, the estimated incidence in children
overall was 0.3 per 100,000 children per year with a mortality of
11.6 %.
•Developed countries – congenital heart diseases with 50 % to 70
% of children had previous cardiac surgery (after 1970)
•Developing countries – rheumatic heart diseases.
•Rare in infancy - usually follows open heart surgery or is
associated with a central venous line.
•Approximately 8% to 10% of cases - without structural heart
disease or other risk factors - usually involves the aortic or mitral
valve secondary to Staphylococcus aureus bacteremia.
•The apparent increase in the incidence of IE in children reflects
increased survival of patients with cardiovascular disease.
•surgery itself, including central vascular catheters, intravenous
alimentation, and days the patient resides in the intensive care
unit are important risk factors
•increasing proportion of children with IE have had previous
corrective surgery or palliative surgical shunt for complex
cyanotic CHD, with or without implanted vascular grafts, patches,
or prosthetic cardiac valves or residual defects [immediate
postoperative period (first 2 weeks after surgery)] even after
surgery
•transcatheter placement of devices such as septal or vascular
occluders and coils - early postdeployment period before
endothelialization has occurred
 NEWBORN INFANTS
•The incidence of neonatal IE has increased in the past 2 decades
•Increasing use of invasive techniques to manage neonates with multiple
complex medical problems, even those with structurally normal hearts
•Staph aureus, coagulase- negative staphylococcus strains, Gram-negative
bacterial species, and Candida species.
•May be indistinguishable from septicemia or from congestive heart failure
•Feeding difficulties, respiratory distress, tachycardia, and hypotension.
•New or changing heart murmur
•Septic emboli - foci of infection outside the heart (eg, osteomyelitis, meningitis,
or pneumonia).
•Neurological signs and symptoms (eg, seizures, hemiparesis, or apnea).
•Arthritis and other immunological manifestations rare
 ETIOLOGIC AGENTS
UNCOMMON: NATIVE VALVE OR OTHER CARDIAC LESIONS
COMMON: NATIVE VALVE OR OTHER CARDIAC Streptococcus pneumoniae
LESIONS Haemophilus influenzae
Viridans group streptococci (Streptococcus mutans, Coagulase-negative staphylococci
Streptococcus sanguinis, Streptococcus mitis) Abiotrophia defectiva (nutritionally variant streptococcus)
Staphylococcus aureus Coxiella burnetii (Q fever)
Group D streptococcus (enterococcus) (Streptococcus Neisseria gonorrhoeae
bovis, Streptococcus faecalis) Brucella
PROSTHETIC VALVE Chlamydia psittaci
Staphylococcus epidermidis Chlamydia trachomatis
Staphylococcus aureus Chlamydia pneumoniae
Viridans group streptococcus Legionella
Pseudomonas aeruginosa Bartonella
Serratia marcescens Tropheryma whipplei (Whipple disease)
Diphtheroids HACEK group
Legionella species Streptobacillus moniliformis
HACEK group Pasteurella multocida
Fungi Campylobacter fetus
Culture negative (6% of cases)
 MICROBIOLOGY
•No relationship exists between the infecting organism and the type
of congenital defect, the duration of illness, or the age of the child
•Staphylococcal endocarditis - no underlying heart disease
•Viridans group streptococcal infection - after dental procedures
•Group D enterococci are - after lower bowel or genitourinary
manipulation
•Pseudomonas aeruginosa or Serratia marcescens - intravenous drug
users
•Fungal organisms - open heart surgery
•Coagulase-negative staphylococci – in the presence of an
indwelling central venous catheter
 PATHOGENESIS
Endothelial Injury

Uninfected Platelet-Fibrin thrombus

(NBTE)

Transient bacteremia and attachment at

NBTE

Proliferation and pro-coagulant state

Infected, friable, bulky vegetation

PATHOGENESIS
PATHOGENESIS OF IE ON PROSTHETIC MATERIAL
•Perivalvular infection -
the sewing ring
•Biofilm formation -
unique and complex
environment for
organisms
•Both antimicrobial agents
and immune cells have
difficulty in penetrating
biofilm
•relapse at a prosthetic
valve site is high
 ORAL/DENTAL CONSIDERATIONS
•Child’s oral flora has a variety of VGS, Neisseria species, Haemophilus species,
and Staphylococcus species
•Older children, species responsible for periodontal diseases (eg,
Capnocytophaga) can be found along with others known to cause IE (eg,
Aggregatibacter actinomycetemcomitans)
•With age - increases in the percentage of VGS, Prevotella, and Actinomyces
species.
•Gingival crevice (subgingival space) - Gram-negative and anaerobic species
•Dental plaque biofilm formation begins soon after a tooth surface is cleaned,
and in the absence of oral hygiene, this biofilm thickens and evolves to include
a more pathogenic bacterial flora largely isolated from the immune system.
•host response to plaque is gingival inflammation and enlargement (gingivitis)
 BACTEREMIA FROM DENTAL PROCEDURES
•Dental procedures are a frequent source of bacteremia
•variable risks are associated with a wide range (0%–97%) in the
incidence of bacteremia in children after various dental procedures and
other manipulations of the gingiva -
tooth extractions (0%–96%)
teeth cleaning and electric toothbrushing (0%–78%)
restorations (16%–66%)
dental injections (16%–97%)
•AHA guidelines have long proposed that maintaining oral health
may be important in the overall effort to prevent IE
•Frequent occurrence of bacteremia with toothbrushing (39% – 46%)
•Data from bacteremia studies strongly suggest that the incidence of
bacteremia annually from toothbrushing and other daily activities far
exceeds that of dental office procedures, perhaps by hundreds of
times per year.
•there has been a steady shift in the direction away from an emphasis
on antibiotic prophylaxis and toward a focus on oral hygiene,
prevention of gingival and dental disease, and access to routine
dental care for children at risk for IE.
 RELATIVE RISK OF ENDOCARDITIS
High Risk
Prosthetic valves
Previous episode of endocarditis
Complex cyanotic CHD ( e.g. ,single -
ventricle states,
transposition of the great arteries,
tetralogy of Fallot
Surgically constructed systemic artery-
to-pulmonary artery shunts
Injection drug use
Indwelling central venous catheters
Moderate Risk
Uncorrected patent ductus arteriosus
Uncorrected ventricular septal defect
Uncorrected atrial septal defect ( other
than secundum )
Bicuspid aortic valve
Mitral valve prolapse with
regurgitation
Rheumatic mitral or aortic valve
disease
Other acquired valvar diseases
Hypertrophic cardiomyopathy
 MORPHOLOGY
•Friable, bulky vegetation containing fibrin, inflammatory cells, and
microbes
•Aortic and mitral valves involved most commonly
•Right side valve involvement in iv drug users
 CLINICAL FEATURES
Related to 4 underlying phenomena:
Bacteremia (or fungemia)
Valvulitis
Immunologic responses
Emboli
•The onset and course vary between 2 extremes
Non specific symptom - low-grade fever with afternoon
elevations, fatigue, myalgia, arthralgia, headache, and, at times,
chills, nausea, and vomiting for as long as several months
Onset may be acute and severe, with high, intermittent fever and
prostration
 RISK FACTORS
Complications Embolization
Prosthetic cardiac valves Vegetations >10 mm,
Left-sided IE Location of the vegetation (mitral
Staphylococcus aureus IE valve anterior leaflet lesions having
Fungal IE a higher rate of embolization than
aortic valve vegetations)(25% versus
Previous IE 10%, respectively).
Prolonged clinical symptoms (>3 mo)
Staphylococci, pneumococci, and
Cyanotic congenital heart disease fungal IE.
Patients with systemic-to-pulmonary
shunts
Poor clinical response to antimicrobial
therapy
 cardiac
•Congestive heart failure
•New or progressive valvular dysfunction
•Periannular extension of infection
•Sinus of Valsalva rupture
•Myocardial dysfunction
•Obstruction of conduits or shunts
•Prosthetic valve dysfunction including
dehiscence
•Pericardial effusion
•Septic emboli to the coronary arteries
extracardiac
•Sepsis
•Immune complex–mediated vasculitis
•Embolic phenomena from septic vegetations –
ischemia, hemorrhage or abscess in
abdominal viscera, brain or heart
•Cerebral, pulmonary, renal, splenic, coronary,
or peripheral arteries
•Stroke, brain abscess, hemorrhage, seizures,
diffuse vasculitis, or meningitis
•Mycotic aneurysms may occur in any systemic
artery or the pulmonary arteries
•Glomerulonephritis secondary to immune
complex depositions
•Classic findings of IE (petechiae, hemorrhages,
Roth’s spots, Janeway lesions, Osler nodes )
 CVS EXAMINATION
•Depends on
Type of heart disease present
The particular site of infection
•Valvular lesions that produce leaflet destruction - Regurgitant murmurs
•New or changing heart murmurs particularly with associated heart failure
•Cyanotic CHD who have undergone systemic-pulmonary artery shunt
procedures - the murmur may not change. Rather, declining systemic
oxygen saturation may reflect graft infection with obstruction of flow.
•Right-sided, catheter-related intravascular infection may have few or no
specific cardiovascular signs or may present with asthma-like symptoms or
signs related to septic pulmonary embolization
•Myocardial abscesses may damage the cardiac conducting system,
causing heart block, or may rupture into the pericardium and produce
purulent pericarditis.
Splinter
hemorrhages
(linear lesions
beneath the nails)
Osler nodes (tender,
pea-size intradermal
nodules in the pads of
the fingers and toes)
Janeway lesions
(painless small
erythematous or
hemorrhagic lesions on
the palms and soles)
Hemorrhagic retinitis with
Roth spots (retinal
hemorrhages with white or
pale centers )
DIAGNOSIS - MODIFIED DUKE CRITERIA
 LABORATORY ASSESSMENT - BLOOD CULTURES
1.Blood cultures should be drawn for patients with fever of unexplained origin and a pathological
heart murmur, a history of heart disease, or previous endocarditis
2. It is reasonable to obtain 3 blood cultures by separate venipunctures on the first day, and if there
is no growth by the second day of incubation, to obtain 2 or 3 more
3. In patients who are not acutely ill and whose blood cultures remain negative, withholding
antibiotic drugs for ≥48 hours while additional blood cultures are obtained may be considered to
determine the cause of IE .
4. In patients with acute IE who are severely ill and unstable, 3 separate venipunctures for blood
cultures should be performed over a short period such as 1 to 2 hours and empirical antibiotic
therapy initiated
5. If fastidious or unusual organisms are suspected, the director of the microbiology laboratory or a
consultant in pediatric infectious diseases should be consulted
6. Culture of arterial blood is not more useful than venipuncture because it does not increase yield
over venous blood cultures, but it is acceptable if only arterial blood samples are able to be
obtained
Automated blood culture monitoring system
 CULTURE-NEGATIVE ENDOCARDITIS (CNE)
•Patient has clinical or echocardiographic evidence of IE but persistently
negative blood cultures.
•The most common causes of CNE are
Current or recent antibiotic therapy
Infection caused by a fastidious organism such as Abiotrophia and
Granulicatella species or an HACEK organism that grows poorly in vitro.
Fungal IE - lower sensitivity of blood cultures for yeast and virtually no
sensitivity for filamentous fungi
Right-sided endocarditis - organisms are filtered by the lungs
Marantic endocarditis
Less common organisms such as Bartonella species, Tropheryma whipplei,
Coxiella burnetii (Q fever), Brucella species, Legionella pneumophila and
Mycoplasma species.
•Molecular techniques to identify16S ribosomal RNA or DNA from
tissue or PCR to detect DNA in blood specimens have identified
agents of CNE on occasion
•Serological methods are often used to diagnose Bartonella
species, T whipplei, C burnetii, Brucella species, and Mycoplasma
species
•Urinary antigen tests are available for L pneumophila serogroup 1
•Autoimmunohistochemistry on surgical specimens
Recommendations
When pediatric patients have suspected endocarditis and have
been treated with antibiotic drugs <4 days but have not had a
prior blood culture, cessation of antibiotic drugs can be useful to
clarify the pathogen’s identity
DIAGNOSTIC TESTS FOR CNE
DIAGNOSIS OF CNE
Complement fixation test (CFT) Brucella microagglutination test
SUPPORTIVE MISCELLANEOUS LABORATORY TESTS
•Anemia of IE - hemolytic or the anemia of chronic disease.
•Acute IE – leukocytosis with immature forms
•Neonates with IE – Thrombocytopenia
•Hypergammaglobulinemia and elevated acute-phase reactants (eg, erythrocyte
sedimentation rate and C-reactive protein)
•Hematuria accompanied by red blood cell casts, proteinuria, and renal insufficiency
in patients who develop immune complex glomerulonephritis
•Hypocomplementemia
•Rheumatoid factor - duration of illness is >6 weeks.
•ECG
•CXR
•CT
Twelve-lead ECG showing acute ST-segment
elevation in leads V1–V3 due to acute myocardial
infarction

Conduction disturbances such as complete

heart block

Direct involvement of the myocardium can

cause serious arrhythmias such as
ventricular tachycardia.
 Myocardial abscesses
due to Staphylococcus
aureus endocarditis

Large myocardial abscesses

Hemorrhagic renal infarct

Diffuse petechial
hemorrhages on the
capsular surface Renal abscesses
of the kidney - the “flea-
bitten kidney”
 Mycotic aneurysms

Embolization and occlusion

of a coronary artery by a
large friable vegetation
 TRANSTHORACIC ECHOCARDIOGRAPHY (TTE)
•Effectively detect endocarditis in young children (up to 97%
sensitivity)(weight <60 kg and age <10 yrs).
•Identify the size, shape, location, and mobility of the lesion
•When combined with Doppler studies, the presence of valve
dysfunction (regurgitation, obstruction) can be determined and
its effect on left ventricular performance quantified
•Helpful in predicting embolic complications, given that lesions
>1 cm and fungating masses are at greatest risk for embolization
•Absence of vegetations does not exclude endocarditis( often not
visualized in the early phases of the disease or in patients with
complex congenital heart lesions)
large vegetation on posterior leaflet of mitral valve large pedunculated vegetation on the aortic valve
large (4 cm diameter) vegetation (VEG) on the tricuspid vegetation on a bioprosthetic aortic valve (single gray
valve arrow) and aortic-root abscess (double white arrows)
Transesophageal Echocardiography (TEE) -
1. Superior to TTE in diagnosing paravalvular leakage or dehiscence
2. Left ventricular outflow tract complications, including aortic root abscesses
3. Involvement of the sinuses of Valsalva
4. Prosthetic valve endocarditis
5. TTE views may be limited –
Chest wall disruptions from previous surgery or from trauma,
Congenital or acquired anomalies of the thoracic cage
Chronic lung disease (limited acoustic windows)
•Intracardiac Echocardiography (ICE) -
Potential pacemaker-lead infections
Post–percutaneous prosthetic valve implantations.
Large mobile vegetation on mitral valve large vegetation on the noncoronary cusp of the aortic
valve
Bioprosthetic mitral valve and paravalvular leak in 2D and 3D TEE
 ANTIMICROBIAL TREATMENT - PRINCIPLES
•In patients who are not severely ill (do not have respiratory or hemodynamic
compromise or change in mental status) and whose blood cultures remain
negative or whose cultures may be positive for organisms that are frequently
contaminants, it is reasonable to withhold antibiotic drugs for ≥48 hours while
additional blood cultures are obtained
•A prolonged course of therapy (at least 4 weeks and often 6–8 weeks)
(?rationale)
•Bactericidal rather than bacteriostatic antibiotic (prevent treatment failure and
relapses)
•Intravenous antibiotic drugs rather than intramuscular (small muscle mass)
(?exception)
•? Outpatient (home) intravenous treatment
•? Additional blood cultures performed after completion of antibiotic treatment
PSSE + Native valve – Pen G 4wks / Pen G or Ceftriaxone + Gentamicin 2 wks
PRSE + Native valve – Pen G or Ampicillin or Ceftriaxone 4 wks + Gentamicin first 2 wks
PSSE + Prosthetic valve – Pen G or Ampicillin or Ceftriaxone 6 wks + Gentamicin first 2 wks
PRSE + Prosthetic valve – Pen G or Ampicillin or Ceftriaxone 6 wks + Gentamicin first 2 wks
(vancomycin in cases of penicillin or ceftriaxone intolerance)
Enterococcus + Native valve - Pen G or Ampicillin + Gentamicin 4-6 wks
Enterococcus + Prosthetic valve - Pen G or Ampicillin + Gentamicin 6 wks
MSSA + Native valve – Nafcillin or Oxacillin 6wks + Gentamicin 3-5 days (optional)
MRSA + Native valve – Vancomycin 6 wks + Gentamicin 3-5 days (optional)
MSSA + Prosthetic valve - Nafcillin or Oxacillin 6wks + Rifampicin 6 wks + Gentamicin 2 wks
MRSA + Prosthetic valve - Vancomycin 6 wks + Rifampicin 6 wks + Gentamicin 2 wks
Gram negative IE (HACEK) – Ceftriaxone 4wks or Ampicillin + Gentamicin 4 wks
STREPTOCOCCAL IE ON NATIVE CARDIAC VALVES
STAPHYLOCOCCAL ENDOCARDITIS ON NATIVE VALVES OR
PROSTHETIC MATERIAL
 GRAM-NEGATIVE IE (EXCLUDING HACEK SPECIES)
•Escherichia coli, Pseudomonas aeruginosa, or Serratia marcescens - rare
causes of IE
•Treatment is individualized according to the judgment of the expert
consultant and guided by identification of the organism and antimicrobial
susceptibility testing
•Nosocomially acquired - unpredictable antimicrobial susceptibilities and
highly resistant
•Extended-spectrum penicillin (eg, piperacillin/tazobactam) or an
extended-spectrum cephalosporin (eg, ceftazidime, ceftriaxone, or
cefotaxime) together with an aminoglycoside for a minimum of 6 weeks of
therapy.
 FUNGAL ENDOCARDITIS
•Medical therapy usually unsuccessful
•Surgery in conjunction with antifungal agents is required
•Amphotericin B has been the first-line antifungal agent
•Addition of 5-fluorocytosine (5-FC; 100–150 mg/kg per day,
divided every 6 hours) to amphotericin B given by mouth for
Candida endocarditis caused by strains susceptible to 5-FC may
provide additional benefit.
•Liposomal forms of amphotericin B alternative for patients
with moderate to severe renal impairment or those with
unacceptable infusion related toxicities.
 CULTURE-NEGATIVE ENDOCARDITIS
Management conundrums –
empirical therapy - may not provide adequate coverage
cause harm secondary to drug adverse events
Considerations of empirical treatment regimens -
important epidemiological factors
?recent antimicrobial exposure before obtaining blood cultures
what specific antimicrobial agent was given
determination of the route of acquisition of microbes
whether the infection was community acquired, nosocomial, or non-nosocomial health care
associated
environmental exposures (including injection drug use)
type of valve infected (whether native or prosthetic)
if prosthetic, how long it had been implanted
the clinical course of infection, whether acute, subacute, or chronic.
Recommendations
1. For CNE, it is reasonable to obtain the proper number of cultures before
antibiotic drugs are begun or to stop antibiotic drugs that were started fewer than
4 days earlier
2. Infectious diseases consultation should be obtained in each case of CNE

Native valve culture-negative endocarditis 4–6 wk

Prosthetic valve culture-negative endocarditis 6 wk
INDICATIONS FOR SURGERY
Vegetation
Persistent vegetation after systemic embolization
Anterior mitral leaflet vegetation, particularly with size >10 mm
≥1 Embolic event during first 2 wk of antimicrobial therapy
≥2 Embolic events during or after antimicrobial therapy
Increase in vegetation size after 4 wk of antimicrobial therapy
Valvular dysfunction
Acute aortic or mitral insufficiency with signs of ventricular failure
Heart failure unresponsive to medical therapy
Valve perforation or rupture
Perivalvular extension
Valvular dehiscence, rupture, or fistula
New heart block
Large abscess or extension of abscess despite appropriate antimicrobial therapy
 PREVENTION OF ENDOCARDITIS
Major revision for antibiotic prophylaxis in 2007-
Random bacteremias associated with daily activities > dental or surgical procedure
Prevent “an exceedingly small” number of cases
Risk of antibiotic-related adverse events exceeds the benefits of prophylactic therapy
Prophylaxis limited to –
Greatest risk of an adverse outcome from IE
All dental procedures that involve manipulation of gingival tissue or the periapical
region of teeth or perforation of the oral mucosa
Prophylaxis for gastrointestinal or genitourinary procedures is no longer recommended
Prophylaxis for many invasive respiratory tract procedures is considered reasonable
Patients undergoing cardiac surgery with placement of prosthetic material is still
recommended.
 ANTIBIOTIC PROPHYLAXIS
Prosthetic cardiac valve or prosthetic material used
for cardiac valve repair
Previous infective endocarditis
CONGENITAL HEART DISEASE (CHD) -
Unrepaired cyanotic CHD, including palliative shunts
and conduits
Completely repaired CHD with prosthetic material or
device- whether placed by surgery or catheter
intervention, during the 1st 6 mo after the procedure
Repaired CHD with residual defects at the site or
adjacent to the site of a prosthetic patch, or
prosthetic device
Cardiac transplantation recipients who develop
cardiac valvulopathy
Oral Amoxicillin 50 mg/kg
Unable to take oral medication - Ampicillin or
cefazolin or ceftriaxone 50 mg/kg IM or IV
Allergic to penicillins or ampicillin—oral
Cephalexin 50 mg/kg or Clindamycin 20
mg/kg or Azithromycin or clarithromycin 15
mg/kg
Allergic to penicillins or ampicillin and
unable to take oral medication - Cefazolin or
ceftriaxone 50 mg/kg IM or IV or
clindamycin20 mg/kg IM or IV
RECENT ADVANCES
darkly staining cocci in a valve-tissue specimen from a patient with infective endocarditis as
revealed by grocott-gomori methenamine silver stain (a) and immunohistochemical detection of
bacteria using the patient’s own serum (b). note the extracellular (asterisk) and intracellular
(arrows) locations of the bacteria revealed by the 2 histologic methods (original magnification,
400 and 200, respectively).
Brucella enzyme immunoassay Polymerase chain reaction (PCR)
FISH IN IE
 ELECTRON MICROSCOPY

TEM from a patient with

BCNE due to T. whippelii.

TEM showing damaged bacterial

cell

SEM showing - Candida

parapsilosis endocarditis
THANK YOU