Article VII.

Infective Endocarditis
1) Infective Endocarditis: definition, etiology, pathogenesis, clinical Pathogenesis
manifestations, diagnostic criteria, differential diagnosis, 1. Vegetative formation
complications and outcomes, treatment.  Main lesion that is composed of thrombocyte aggregation +
platelet + fibrin deposits on surface of valve
Definition  Infectious microorganisms are inside thrombus
Infectious inflammation of endothelial lining of heart (endocardium)  Needs 2 conditions
a) Bacteremia: after brushing teeth, defecation of microbes
Etiology leads to minimal injury
1. Infection - Healthy people → eliminate it
- Bacteremia - Immunodeficient people → risk of platelet aggregation +
(Streptococci, Staphylococci, Enterococci, P. aeruginosa) thrombosis
- Fungi < common b) Disturbance of blood flow due to thrombus formation
2. Turbulence flow + damage of endothelium  If there is vegetation, there is problem for antibiotics usage &
- Any valvular diseases, any abnormalities of heart (eg: mitral immune system because microorganisms are inside thrombus
valve prolapse, congenital heart diseases, pre-existing & thus, disabling the immune system cells from suppressing it
rheumatic fever or valvular diseases)  Eg: in case of drug abuse, there is risk for platelet aggregation &
- 2nd/3rd grade of regurgitation → risk of IE is 6-8x higher fibrin deposits → vegetation causing embolism (septic &
3. Insufficiency of immune system aseptic) & valve dysfunction (also caused by valve leaflet
dysfunction) → hibernation of microbes in vegetation →
Predisposing/risk factors ineffective immune system & susceptibility to antibiotics
1. Colonization/local factors
- Hypertrophic cardiomyopathy 2. Destruction of not only valves but also all other structures (firstly,
- Prosthetic valves valve then, myocardium, pericardium) & septic complications
- Implanted pacemakers  Infective organisms are constantly present on valve, and cannot
- Congenital heart defects be removed (there is bacteremia & colonization of all valves,
- Valvular diseases mitral, aortic, pulmonary, tricuspid or combined)
- Calcification  Cause destruction of structures near thrombus
- Mitral valve prolapse  > formation of valve disease

2. Factors causing bacteremia  Mass on valve → danger of destruction of mass on valve +

- Infusion of medical drugs (catheterization of big veins or IV particles may pass through blood flow → systemic circulation
(high risk of thromboembolism in any organs, eg: brain,
catheterization)
kidney, heart, etc) causing infarction → abscess due to
- Narcotic use (blood flow during infection → RA → RV →
thromboembolism + infection → sepsis
damage of endothelium → endocarditis of tricuspid valve)
- Dental procedures, eg: extraction (in 80% cases)
3. Immunologic phenomena
- Surgical procedures in ENT, eg: tonsillectomy
 If infection is not removed properly → persistent for long time
- Chronic bacterial infections
→ difficult for immune system activity
- Acute diseases, eg: p
 Constant bacteremia → immune hyperactivity → immune-
- Sometimes, simple endoscopy mediated infective endocarditis
- Every manipulation of upper part of body  If prolonged → pathological immunologic phenomena →
aseptic GN, splenomegaly, Rh factor +ve, SC nodules due to
3. Decreased immunity vasculitis (Osler’s nodes)
- AIDS, DM, cytostatics, corticosteroids, malignancies
Classification
Groups of risk A) Course
1. Acute Infective Endocarditis
HIGH RISK MODERATE RISK LOW RISK - Course of disease not more than 2 months
 Prosthetic valves  PDA  Isolated/small ASD - If no treatment → patient may die
 Episodes of  VSD/ASD  ≠ septal defects upto - If patient is treated, disease rarely lasts longer than 2 months
endocarditis  Coarctation of 6 months after - Most common: Staphylococcus aureus, others possible too
 Congenital heart aorta operation - Usually occurs on previously normal valve
defects (Tetralogy  Bicuspid aortic  Innocent heart - Vegetation is usually relatively large in diameter, >3mm
of Fallot) valve murmurs in pediatric
- Complications:- purulent complications > typical
 Surgically  Hypertrophic population
immunologic complications < typical
constructed cardiomyopathy  Pacemaker
systemic &  Acquired valvular  2 months after
2. Subacute Infective Endocarditis
pulmonary shunt dysfunction operation
 Course: during 2-9 months, prolonged course
 Infarction
 Gradual onset
 Mitral valve
 Cause: Streptococcal infection
prolapse
 Occurs on previously changed valve, i.e. in pt with RF
 2nd degree mitral
 Vegetation is usually relatively small in diameter
regurgitation
 Purulent complications are not typical
Immunologic complications are typical
 o Eg: if mitral and aortic valves are involved, systemic
circulation will be affected & if tricuspid, pulmonary
B) According to features of valve circulation
 Native valve endocarditis
- Occurs on patient’s own valve
- Due to:- 4. Immune-mediated symptoms (signs of vasculitis)
a) IV drug abuse → H. influenza, Staphylococcus  Roth spots = retinal hemorrhage visible by fundoscopy; cause
b) Nosocomial infections decrease in vision
o depend on types of procedures:  Lutkin-Libman spots = hemorrhage on conjunctiva
o If GU or GIT → due to Gram negative microbes  Osler’s nodes = painless, small-sized nodules (2cm) at
o If respiratory or upper GIT → due to Staphylococcus, periarticular tissues
Streptococcus, H. influenza  Painful, red, subcutaneous nodes on skin or hands
 Prosthetic valve endocarditis  Rumel-Leede Kanchilovsky sign = appearance of hemorrhagic
- Most commonly due to Streptococcus, Staphylococcus rash upon releasing BP after measuring up to 200 mmHg that
- 2 types:- develops in 1 min time (mechanism:- measure BP up to 200 →
a) Early (First 3 months after replacement) hemodynamic trauma of small vessels → rash upon releasing)
b) Late  All these later lead to different organ or immune damage
eg: GN, reactive oligoarthritis
C) → Primary (occurs at previously non-damaged valve)
→ Secondary (occurs at previously damaged valve) ACUTE INFECTIVE ENDOCARDITIS
→ Prevalence of symptoms (1) + (2) + septic embolism
D) Etiologic classification:-  Begin very rapidly; toxicity & high fever (> 38°C)
 Staphylococcus, Streptococcus, H. influenza, Legionella, Fungi,  Intoxication symptoms eg: headache, nausea, vomiting,
Enterococcus, etc arthralgia, pain in muscle, skin manifestations (petechial
lesions), tachycardia
E) Complications:-  Other complications are possible except thromboembolism &
 Purulent + paravascular abscess, intraseptal abscess abscess
(purulent pericarditis, abscess of myocardium or other organs) - Roth spots, petechial lesions (>common), splinter
 Sepsis hemorrhage
 Arrhythmia (especially AV block) - Janeway lesion = red macule, mainly on palm (thenar &
 Thromboembolic complications (stroke, brain/renal infarction) hypothenar eminence)
 Immunologic complications (hypersplenism, GN, vasculitis, - Osler’s nodule
etc) - Hard, painful, tender, subcutaneous swelling on fingers, toes,
palms, and soles
Diagnosis - SC nodule (relatively small in size, maybe larger than 2mm,
Infective endocarditis, acute, S. aureus, primary, complicated by AV usually in periarticular external surface
block 3rd degree, CHF, functional class 4  After 5-7 days, clinical manifestations of heart disorders maybe
found:-
Clinical Features - Heart failure
Altogether there are 4 main types of symptoms according to - Different degrees of dyspnea
pathogenesis:- - Arrhythmia
1. Non-specific symptoms connected to infection → Physical signs
 Fever, malaise, myalgia, arthralgia, loss of weight,  Murmur
splenomegaly, lymphadenopathy - Systolic murmur if mitral regurgitation is the cause; best
 If persistent → cause multisystem failure such as kidney & liver auscultated at apex with conduction to axilla & maybe
failure pansystolic, maybe functional or organic
2. Symptoms connected to valve dysfunction - Diastolic murmur which is not functional & always organic,
 Appearance of new, changing murmur & later, HF more commonly of aortic regurgitation; best heard at L
3. Embolic symptoms borderline of sternum, conducted to carotid, better heard at
 Septic or infective emboli cause peak of expiration & if present, there is high suspicion of
o Janeway lesion (purple/red maculopapular rash on infective endocarditis
thenar/hypothenar of palms)  Others depend on complications!
o Abscess of different organs eg: brain, kidney, heart (may  Size of heart, at first maybe without changes, but later, may
cause paravalvular abscess → rupture of valves + intraseptal enlarge due to involvement of valve
abscess → septal rupture & defect + ventricular abscess)
o Pneumonia if tricuspid valve is involved SUBACUTE INFECTIVE ENDOCARDITIS
o Infective monoarthritis if joint is affected → Prevalence of symptoms (4) + aseptic embolism + general
 Aseptic emboli cause characteristics such as subfebrility in which patient is firstly admitted
o Spleen, kidney infarction, MI, Stroke with fever of unknown origin, later, development of multisystemic
o Emboli maybe small & embolize small arteries that supply big organ failure & slowly progressive HF
arteries causing mycotic phenomena or mycotic aneurysm,  Onset > gradual, fever usually subfebrile, complaints mild
eg: aseptic embolism of vaso vasorum → mycotic aneurysm  Toxicity > common, loss of weight, loss of appetite
→ rupture & hemorrhage → intracranial hemorrhage →  At least 2 weeks to cause some manifestations
neurological symptoms  Cardiac symptoms at least 2 weeks or more after infection (in
 Symptoms depending on types of valve involved acute IE, cardiac manifestations in 5-7days) with manifestations
of HF, murmur, arrhythmia
  Immune problems possible: Roth spots, GN, HSM (maybe due - ESR ↑
to immunological phenomena; HF or micro-abscess formation 3. Microbiological/blood criteria
& in this case), SC nodules, RFx maybe +ve, arthralgia, synovitis, - If 2 +ve results of typical
hemorrhagic lesions blood cultures
 If long course of disease without treatment → can see clubbing - 2 +ve cultures with interval
fingers due to hypoxia of 12 hrs for same organism
Investigation - 3 +ve cultures with interval
1) Blood analysis of 1 hr
 Anemia always (splenomegaly, hemorrhage)
 ESR increase (inflammatory changes in blood is typical) * Blood culture is taken normally not from a single vein but from 3
 Leukocytosis with L shift of neutrophils portions of different veins, but thrombophlebitis may occur, so take
 RFx +ve in 50% of patients blood thrice with volume of 15-20 ml with pause of 15 min from
 Circulating immune complexes increase different sites. If 2 or all 3 samples are +ve, it is major; if only 1,
2) Blood culture repeat & if still only 1 +ve then it is minor.
 At least 3 analyses (15-20ml) with pause 15 min, obtained However, in case of microbes that are difficult to be identified by
from different veins done before antibiotics usage culture eg: Coxiella burnetii, only 1 +ve culture (> or equal 800) is
 To exclude false +ve → take when increase T in the evening enough for major criteria.
 If only 1 +ve, repeat the test
3) Urine analysis Diagnosis
 Proteinuria typical (toxicity) 2 major (1 from blood, 1 from echo criteria) @
 If infection in kidney: leukocytes, erythrocytes, protein in urin 1 major + 3 minor @
 If GN: hematuria 5 minor
4) Biochemistry
 CRP +ve Treatment
 Depends on organisms & which organs are involved → liver 1) Antibiotic treatment
function test (increase in AST, ALT, urea, creatinine levels, etc)  Acute
5) Serology - Start immediately after obtaining 2 blood analyses
 Increase in C3, C4  Subacute
6) Cardiac enzymes are increased in infarction, abscess of - If patient’s condition is satisfactory, wait for result of culture
myocardium, myocarditis - If rather severe, do not wait
- Antibiotics are given in injection form
Instrumental investigation - Duration of course should be significant, as in a few weeks,
1) Echocardiogram
months or more, under control of general condition, blood
 Visualization of vegetation (problem: cannot visualize
culture & blood analysis
vegetation < 3mm)
 2 types (transthoracic & transesophageal if right heart failure
 Empirical treatment / Blind therapy
because right heart is poorly visible with transthoracic
- Depends on Methicillin-resistant Staphylococcus aureus
method) to observe vegetation, abscess & valvular
(MRSA)
dysfunction
- If MRSA absent, all Beta-lactams can be administered
 Valvular involvement
- In case of susceptible patients, Cephalosporin &
 Abscess
Aminoglycoside can be used against P. aeruginosa if low
 Doppler echocardiogram:- pathological blood stream, ejection
susceptibility; Vancomycin & Aminoglycoside if high
fraction, heart chamber dilatation
susceptibility
2) ECG
 Arrhythmia, AV block common
 If suspect Streptococcal infection
 Metabolic disturbances
o Beta-lactams
3) Other methods depending on affected organs (abdomen CT,
Cephalosporin
USE)
- Ceftriaxone 1-2g IV bid
Duke criteria (Durack = 1st author) → for diagnosis of IE - Cefotaxime 1g IV, IM bid

MAJOR MINOR  If suspect Gram -ve microflora

- Start combination of Beta-lactam + Aminoglycoside
1. Echo - Fever > 38°C
- Presence of vegetation, (Gentamicin 80mg bid; If suspect Staphylococcus: 160mg IV
- Embolic manifestations
bid or tid)
selected mass - History of valve disease
- Alternative variant: Vancomycin 1g bid
- Myocardial abscess, purulent - Arthralgia
pericarditis - Immunologic phenomena,
 If suspect infection of heart is of pulmonary origin (severe
- Related prosthetic valve vascular phenomena,
pneumonia) → can suspect Legionella, Mycoplasma as
dysfunction (commonly petechial lesion
microorganisms which cause pneumonia → better use
involved in IE) - Microbiological criteria that
o Fluoroquinolone
do not meet major criteria eg:
- Levofloxacin 0.5g IV slowly sid
2. Physical findings if only 1 +ve blood culture
- Newly developed diastolic - Moxifloxacin 0.4g IV slowly sid
- ECG → AV block 3rd degree
murmur (not worsening of o * Macrolides
- Echo changes that do not
previously existing murmur; o *Beta-lactams are not effective for Mycoplasma
meet major criteria
new onset of regurgitation) - CRP +ve
 If suspect infection is of GIT or genitourinary origin
 → more common Enterococcus & Proteus  Better care during insertion and handling of intravascular catheter
and prompt removal
 If suspect Staphylococcal infection → MRSA  If manipulation on lower part of body
- Vancomycin 1g bid o Fluoroquinolone
- Oxacillin ≥ 4g/d IV 4 hourly (high dose) - Ciprofloxacin 0.5g bid (12hr after 1st dose)
- Imipenem (Carbapenem) 0.5g bid or tid - Noproxacin
- Levofloxacin
 If suspect fungal infection in AIDS patients
- Toconazole

 It is necessary to control effects of antibiotics for 3-5 days

Treatment is effective if
- Symptoms of fever, dyspnea, etc become less significant
- Echo reveals decreased volume of vegetation Prognosis
 If not, treatment is not effective and it is necessary to change Worse if
antibiotics according to culture results & if all measures are not - Acute or S. aureus endocarditis
effective, operation is indicated - When HF present
 Usually after 5-7 days, effectiveness will be known (according to - When infection occurs on prosthetic valve
culture results) - When microorganisms found are resistant to therapy
 Minimal duration of the whole course is 6 weeks with at least 3
weeks of normal temperature (Why? Because microbes may Causes of death
hibernate in body) 1. Acute heart failure (due to acute rupture of valve → valvular
problem + lung edema without antibiotics + severe infection)
2) Symptomatic treatment 2. Severe infection → infectious shock
 Heart failure → ACE inhibitors, Diuretics, etc 3. Embolism → pulmonary embolism, stroke, renal failure
 Arrhythmia → Antiarrhythmic drugs 4. Pneumonia (secondary)
 Fever → Antipyretics (Aspirin, Ibuprofen, Diclofenac, Nimesulid 5. Renal failure
 Shock (decreased BP) → IV infusion of 5% glucose or 0.9% NaCl
+ Diuretics + coffee (funny idea) # Clinical situation maybe different without proper treatment;
without antibiotics, mortality is 100% in 1 year, and even longer in
3) Operation case of infection with Streptococcus viridans
If all drugs are not effective, operation must be done If there is long course of S. viridans infection without treatment →
- Removal of infectious agents with vegetation + replacement hypoxia → clubbing fingers
with artificial valve

Indications for surgery Part III

1. Extensive damage of valve 34) Diagnostic search in patients with infective endocarditis in
2. Prosthetic valve endocarditis → valve replacement is usually polyclinic
required - For this question, know all aspects of infective endocarditis
3. Persistent infection despite therapy or after 3 days of treatment (refer question 1)
4. Serious embolization → septic emboli
5. Large vegetations
6. Myocardium abscess → abscess d/ment → constant source of
bacteremia (if spleen → removal; if brain → treat it)
7. Fungal endocarditis
8. Progressive heart failure
9. Acute rupture of valve
10. Infectious endocarditis before

Prophylaxis
Antibiotic prophylaxis
 For high and moderate risk, eg: prosthetic valve, native valvular
disease, history of infective endocarditis, congenital heart defects,
mitral valve prolapse and calcification or regurgitation,
hypertrophic cardiomyopathy → antibiotics should be taken
before any procedures connected with GIT (mostly Gram -ve),
urogenital tract, oral cavity, ENT, upper GIT, respiratory tract and
different manipulations of upper part of body
 People with vascular lesion before undergoing procedures such as
dental treatment, surgical intervention should have antibiotic
prophylaxis (1hr before, 4-6hr after)
- Amoxicillin 500mg
- Clarithromycin/Azithromycin/Erythromycin 0.5g PO
(Macrolides)
 Meticulous oral and skin hygiene