Infective Endocarditis

 Refers to microbial invasion of the heart valves or mural endocardium—

characteristically results in formation of bulky friable vegetations, composed of mass
of platelets, fibrin, microcolonies of organisms, and scanty inflammatory cells.
 Vegetations are most commonly present on the heart valves, followed by the low-
pressure side of a ventricular septal defect, and on the mural endocardium.

Classification
Based on rapidity of evolution, severity of infection and virulence of the implicated
organism:

 Acute Endocarditis: Spreads to extracardiac site

 Subacute Endocarditis: Typically has an insidious onset, metastasizes slowly and is
gradually progressive over weeks to months; most patients recover after appropriate
antibiotic therapy

Pathogenesis
Following sequential steps:
 Underlying risk factors:
 Underlying cardiac defect: Most common cardiac conditions associated with
infective endocarditis are congenital valvular diseases such as mitral
regurgitation, aortic stenosis, aortic regurgitation, ventricular septal defects
 Use of intravenous catheter
 Prosthetic valve replacement surgery.
 Endothelial injury: The endothelium, unless damaged, is resistant to infection by
most bacteria and to thrombus formation - Therefore, though IE can develop on
previously normal valves, but it is more common to develop on a defective valve
 Predisposing Cardiac Abnormalities

Turbulence in blood flow

Use of IV catheter – direct trauma

Damage to cardiac endothelium that can damage cardiac
endothelium

Deposition of Platelets and fibrin Nonbacterial thrombotic

endocarditis (NBTE).

 Colonization: Thrombus - serves as a site of bacterial attachment - When bacteria

transiently gain access to the bloodstream (e.g. after brushing the teeth), the
organisms may stick to and then colonize the damaged cardiac endothelial surface
 Formation of vegetations:

Colonisation
This web of platelets, fibrin,
Covering of endothelial with a inflammatory cells, and
protective layer of fibrin and platelets entrapped organisms is called as
vegetation

Protective Environment – Favourable

for further bacterial multiplication

 Metastasis: Vegetations ultimately seed bacteria into the blood at a slow but
constant rate, which can metastasize to distant sites.

Etiological Agents
 Differ depending on the underlying risk factors such as native or prosthetic valve IE,
acute or subacute IE, other risk factors such as IV drug abuser.
 The organisms differ from each other in their primary portal through which they
enter into the bloodstream and reach to the heart; for example
 Oral cavity- for viridans streptococci
 Skin for staphylococci
 Upper respiratory tract for HACEK organisms
 Gastrointestinal tract for Streptococcus gallolyticus and enterococci.
Clinical Manifestations:
 Cardiac manifestations - Appearance of a new/worsened regurgitant murmur, which
is more useful for the diagnosis of IE involving a normal valve
 Noncardiac manifestations - Fever, chills and sweats, anorexia, weight loss, myalgia,
arthralgia, arterial emboli, splenomegaly, clubbing, petechiae, neurologic
manifestations and peripheral manifestations (Osler’s nodes, subungual
hemorrhages, Janeway lesions)
 Laboratory manifestations: Anaemia, leucocytosis, microscopic hematuria, elevated
ESR, CRP, or rheumatoid factor.
Diagnosis:
 Modified Duke Criteria:

Blood Cultures:
 Isolation of the causative microorganism from blood cultures - Critical for diagnosis,
determination of antimicrobial susceptibility, and planning of treatment.
 Blood cultures should be collected before antibiotic therapy.
 Two blood culture sets should be collected at an interval of >12hr between 1st and
2nd set
 Alternatively, three blood culture sets can be collected over one hour (e.g. 30 min
gap between 1st and 2nd set and 30 min gap between 2nd and 3rd set).
 Blood culture set refers to ‘pair of bottles’; collected from different venipuncture
sites.

Non-blood-culture Tests:
  Serologic tests - Used to implicate some organisms that are difficult to recover by
blood culture - Brucella, Bartonella, Legionella, Chlamydophila psittaci, and Coxiella
burnetii
 Isolation of the pathogens in vegetations by culture
 Microscopic examination with special stains (e.g. periodic acid–Schiff stain for
Tropheryma whipplei)
 Direct fluorescence antibody techniques
 PCR to recover unique microbial DNA or 16S rRNA that, when sequenced, allows
identification of the etiologic agent.

Echocardiography:
 Allows anatomic confirmation of infective endocarditis, sizing of vegetations,
detection of intracardiac complications, and assessment of cardiac function.

Staphylococcal Endocarditis
 S. aureus - Most common cause - usually runs an acute course.
 Larger vegetations (>10 mm in diameter) - More frequently associated with
features of septic embolization (due to breaking of vegetations leading to
formation of emboli) such as subungual haemorrhage, Osler’s nodes, etc.
 Cerebrovascular emboli can cause strokes or occasionally encephalopathy
  Embolization risk is higher for mitral valve IE.
 S. aureus - Gram-positive cocci arranged in cluster, produces golden yellow
hemolytic colonies on blood agar and gives a positive coagulase test
 Coagulase-negative staphylococci (e.g. S. epidermidis) - Associated with prosthetic
valve endocarditis (at least 68–85% of cases) and majority of them are methicillin
resistant

Viridans Streptococci
 Commensals of mouth and upper respiratory tract.
 Usually, nonpathogenic
 Occasionally cause diseases such as:
 Subacute bacterial endocarditis (SABE) - Most common cause of SABE.
o Commensal viridans streptococci (S. sanguinis) in the oral cavity can
enter blood to cause transient bacteraemia while chewing, tooth
brushing and dental procedures
 Dental caries: Mainly caused by S. mutans - Breaks down dietary sucrose to
acid and dextrans with the help of an enzyme glucosyl transferase.
o Acid damages the dentine, while adhesive dextran binds together with
food debris, mucus, epithelial cells and bacteria to produce dental
plaques
 In cancer patients: Viridans streptococci can cause prolonged bacteraemia
 S. milleri group - (includes S. intermedius, S. anginosus, and S. constellatus):
Produce suppurative infections, particularly brain abscess and empyema.
 Laboratory Diagnosis
 Gram stain - Gram-positive cocci arranged in long chains
 Produce minute D-hemolytic green-colored (rarely non-hemolytic) colonies
on blood agar (“viridis” means green)
 Differentiated from Streptococcus pneumoniae (which is also D-hemolytic) by
a number of tests such as resistant to optochin and insoluble in bile
 Accurate species identification is made by automated methods such as
MALDI-TOF

Nutritionally Variant Streptococci:

 Abiotrophia and Granulicatella species - Nutritionally variant streptococci as they
require vitamin B (pyridoxal) in the culture medium for their growth. Earlier grouped
along with viridans streptococci
 Normal inhabitants of the oral cavity
 Diagnosis: Can be recovered in automated blood cultures such as BacT/ALERT -
Multiple blood cultures and prolonged incubation may be necessary
 Fail to grow when sub cultured on solid media.
  Sometimes produce satellite colonies near the colonies of “helper” bacteria
(e.g. near Staphylococcus aureus streak line) - Also called as Satelliting
streptococci
 Catalase negative, gram-positive cocci arranged in short chains
 Species identifcation - By automated systems such as MALDI-TOF.
 Treatment: Combination therapy with penicillin plus gentamicin is
recommended for IE cases.

S. gallolyticus Endocarditis
 S. gallolyticus (formerly S. bovis) - Group D Streptococcus - found as a commensal in
intestine of animals.
 In humans, it occasionally causes bacteremia, subacute endocarditis, and also
associated with colorectal cancer or polyps.
 Penicillin is the drug of choice
HACEK Endocarditis
 HACEK - Represent a group of highly fastidious, slow-growing, capnophilic,
gramnegative bacteria, that normally reside in the oral cavity as commensal, but
occasionally have been associated with local infections of the mouth and systemic
infections such as bacterial endocarditis.
 Species belonging to this group include:
 Haemophilus parainfuenzae
 Aggregatibacter species: A.actinomycetemcomitans, A.aphrophilus and
A.paraphrophilus
 Cardiobacterium hominis
 Eikenella corrodens
 Kingella kingae.
 HACEK - Accounts for 3% of total endocarditis cases - Typically has a subacute course
 Occurs in patients with preexisting valvular defects or those undergoing dental
procedures
 The aortic and mitral valves are most commonly afected.
 Clinical Manifestations
1. Haemophilus parainfuenzae:
 Commensal in mouth and throat
 Occasionally an opportunistic pathogen causing endocarditis,
conjunctivitis, abscesses, genital tract infections and
bronchopulmonary infections in patients with cystic fbrosis
 Diferentiated from H. infuenzae either by its growth requirement
(requires only factor X, but not V), or by automated identifcation
systems such as MALDI-TOF or VITEK.
2. Aggregatibacter species:
 a) Aggregatibacter actinomycetemcomitans: Formerly called as Actinobacillus
actinomycetemcomitans
 Most common member of HACEK to cause endocarditis
 Can also be isolated from soft tissue infections and abscesses
associated with Actinomyces israelii
 Rarely, it can cause periodontitis, brain abscess, meningitis and
endophthalmitis
b) Aggregatibacter aphrophilus and A. paraphrophilus: Earlier members of
Haemophilus, now are renamed under genus Aggregatibacter
 Commensals of mouth and occasionally cause endocarditis, head and
neck infections, invasive bone and joint infections
 A. aphrophilus requires only factor X, whereas A. paraphrophilus
requires only factor V.
3. Cardiobacterium hominis: Frequently affects the aortic valve - Also
associated with arterial embolization, immune complex glomerulonephritis or
arthritis
4. Eikenella corrodens: Apart from endocarditis, it can also occasionally cause
skin and soft tissue infections.
 The name ‘corrodens’ refers to the characteristic pitting or corroded
colonies on blood agar
5. Kingella kingae: In addition to endocarditis, it can also cause infections of
bones, joints and tendons.

 Laboratory Diagnosis
 Culture: Blood cultures are performed on automated systems such as
BacT/ALERT - Highly fastidious, require multiple blood cultures, and
prolonged incubation up to 1 week
 They are capnophilic, growth is optimum in presence of 5–10%
of CO2
 Identifcation is made by automated systems such as MALDI-
TOF.
 Molecular methods: Simultaneous detection of HACEK members from
clinical specimen is possible by performing
 Broad-range bacterial PCR targeting 16S rRNA gene followed
by sequencing
 Multiplex PCR or multiplex real-time PCR.