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Infective Endocarditis
Infective Endocarditis is defined as infection of the endocardial surface of the
heart which might also involve the heart valves. Valves involved in Infective
Endocarditis in descending order of frequency are the mitral valve, followed by aortic valve,
followed by combined involvement of mitral and aortic valves, followed by tricuspid valve and
rarely the pulmonic valve is involved.
The pathomechanism by which Infective Endocarditis is thought to occur is
that, turbulence of blood flow in the heart for instance due to underlying
valvular abnormality is thought to cause injury to the endothelial surface of
the heart, which allows either direct infection of the endocardium or it can
cause development of uninfected platelet/fibrin thrombus (a condition known
as nonbacterial thrombotic endocarditis) and the thrombus might
subsequently serve as a site of bacterial attachment during transient
bacteremia and could end up causing infection of the endocardial surface of
the heart.
Predisposing factors for Infective Endocarditis include:
-Rheumatic heart disease which accounts for about 20%of cases of Infective Endocarditis
-age related degenerative valve disease particularly calcific aortic stenosis accounting for about
50 % of cases of Infective Endocarditis
-congenital heart disease accounts for about 15% of cases of Infective Endocarditis, bicuspid
aortic valve being the commonest congenital heart disease associated with Infective Endocarditis
-residual valve damage from previous episode of endocarditis
-in young adults, the commonest predisposing condition is Mitral Valve Prolapse, accounting for
about 30% of cases of endocarditis in this age group
-assymetric septal hypertrophy involving the mitral valve accounts for about 5% of cases of
Infective Endocarditis
-illicit intravenous drug use
-presence of intracardiac devices for instance pacemaker or defibrillator wire or presence of
artificial (prosthetic) valve
- and presence of intravascular devices for instance central or peripheral intravenous catheters or
presence of hemodialysis shunts or catheters.
Infective endocarditis can be classified into the following five categories:

1-Native valve endocarditis ( Acute and Subacute )

2-Prosthetic Valve endocarditis
3-Intravenous drug use associated endocarditis
4-Pacemaker associated endocarditis
5-Health care associated Infective Endocarditis
1-Native valve endocarditis as the name implies involves natural, not artificially implanted
valves. Acute native valve endocarditis often involves normal natural valves. Subacute native
valve endocarditis often involves abnormal natural valves for instance valves involved by
rheumatic heart disease.
The commonest causative organism of native valve endocarditis accounting for 70% of cases is
Streptococcus species, including Streptococcus Viridans, Streptococcus Bovis and Enterococcus.
Staphylococcus accounts for about 25% of cases of Native valve endocarditis.
2-Prosthetic valve endocarditis as the name implies occurs in individuals who had artificial
(prosthetic) valve implanted for stenotic or regurgitant valve lesions.
The commonest causative organism of Prosthetic valve endocarditis is Coagulase negative
Staphylococcus accounting for about 30% of cases, the second commonest cause accounting for
about 12-17% of cases is Staphylococcus Aureus.
There are about 31 species of Staphylococcus, two of which (Staphylococcus aureus and
Staphylococcus Intermedius) produce an enzyme that could cause coagulation, known as
Coagulase, and are therefore classified as Coagulase positive Staphylococcus. The rest 29
species dont produce Coagulase enzyme and are hence known as Coagulase negative
Staphylococcus. The commonest Coagulase negative Staphylococcus, isolated from more than
75% of clinical specimen is Staphylococcus epidermidis.
3- Infective Endocarditis associated with intravenous drug use as the name implies occurs in
association with illicit intravenous drug use. It often involves the tricuspid valve and the
commonest causative agent accounting for close to 50% of cases is Staphylococcus Aureus.
Other organisms that could cause IV drug use associated endocarditis include group A, C and G
Streptococcus, Enterococcus, Pseudomonas, the HACEK organisms which stands for
(Hemophilus, Actinobacillus, Cardiobacterium, Ekinella and Kingella), and even fungal
pathogen could cause Infective Endocarditis in association with IV drug use. The commonest
fungal pathogen that could cause endocarditis are Candida and Aspergillus species.
4-Pacemaker associated Infective Endocarditis as the name implies occurs in individuals who
had Pacemaker implanted for bradyarrythmias or in individuals who had defibrillator implanted

for tachyarrythmias. The commonest pathogen causing pacemaker associated Infective

Endocarditis is Staphylococcus, both coagulase negative and coagulase positive.
5-Health care associated Infective Endocarditis is defined as Infective Endocarditis occurring
within four weeks of undergoing intravascular device placement, for instance placement of
central or peripheral intravenous catheter placement, or following placement of hemodialysis
shunt or catheter. The commonest causative organism of health care associated Infective
Endocarditis is again Staphylococcus Aureus followed by Enterococcus. Enterococcus often
arise from genitourinary source.
Clinical Manifestation
Subacute Infective Endocarditis has indolent gradually progressive course, which causes slowly
progressive valvular destruction occurring over several months.
Some of classical signs of subacute Infective Endocarditis which occur due to immune mediated
vasculitis include, petechia, subungual(splinter) hemorrhage, Osler nodes and Roth spots.
Petechia occur in 20% of cases with Infective Endocarditis and often involves the palpebral
conjunctiva, dorsum of the hands, feet, the anterior chest and abdominal wall, the oral mucosa
and soft palate.
Subungual splinter hemorrhage are linear hemorrhage occurring under afinger or toenail.
Subungual splinter hemorrhage could also occur due to trauma, the difference is subungual
hemorrhage due to Infective Endocarditis doesnt extend over the entire length of the nail,
whereas subungual hemorrhage due to trauma often involve the entire length of the nail.
Osler node is tender nodule over the pulp of the finger or toe or over the thenar or hypothenar
eminences of the hands.
Roth spots are retinal hemorrhages with pale centers.
One or more of the above classical signs of subacute Infective Endocarditis might be noted in
upto 50 % of cases with subacute Infective Endocarditis.
Other immunologic manifestation in individuals with subacute Infective Endocarditis is
glomerulonephritis due to deposition of immune complex in the glomerular basement membrane.
On the other hand Acute Infective Endocarditis as the name implies has a rapidly progressive
course, with acute onset of high grade fever, chills and rapidly progressive destruction of
infected valves causing rapid onset CHF and might progress to death within weeks.
In acute Infective Endocarditis, a painless 1-4 mm sized hemorrhagic macule known as
Janeways lesion may be noted over the palms and soles, which is thought to occur because of
vasculitis of cutaneous vessels due to embolization of infected microemboli in the cutaneous

vessels. But immunologic manifestation which are characteristic of subacute Infective

Endocarditis, including petechia, subungual hemorrhage, Osler nodes and Roth spots are often
absent in acute Infective Endocarditis, the reason is because of shortened clinical course of acute
Infective Endocarditis, immune reaction to the infection might not have developed.
Complications of Infective Endocarditis include:
1-the commonest complication of both acute and subacute Infective Endocarditis is CHF due to
valvular insufficiency, which occurs because of destruction of valve leaflets or because of
destruction of papillary muscle or chordae tendineae, but Infective Endocarditis could also cause
narrowing of valves because of formation of large vegetation.
2-the second commonest complication of both acute and subacute Infective Endocarditis
accounting for 15-35% of cases is arterial embolization. Embolization from right sided
endocarditis could cause septic pulmonary emboli and pulmonary infarct which may be
manifested with multiple nodular infiltrate and occasionally might cause pyopneumothorax.
Embolization from left sided endocarditis could involve cerebral vessels, retinal or coronary
arteries and could cause CVA, unilateral blindness or myocardial infarction respectively.
Embolization from left sided endocarditis could also cause multiple abscess in almost every
organ including the brain, heart and kidney. If septic arterial embolization gets lodged on a vessel
wall or if it involves arterial supply (vasa vasorum) of an artery, it could cause weakening and
focal dilatation of the involved artery which is known as mycotic aneurysm. Vessels where
mycotic aneurysm commonly occurs include, cerebral vessels, the splenic, coronary and
pulmonary arteries.
3-extension of the infection beyond valve leaflets into adjacent annular or myocardial tissue can
result in perivalvular abscess which in turn may cause intracardiac fistula with new murmur.
4-abscess may also burrow from the aortic valve annulus through the epicardium and might
cause pericarditis.
Diagnosis
Diagnosis off Infective Endocarditis is made by what is known as Duke criteria, which has two
major and five minor criteria based on clinical, laboratory and echocardiographic findings.
The major criteria include, 1- positive blood culture for microorganisms that commonly cause
Infective Endocarditis including Streptococcus Viridans, Staphylococcus Aureus and
Streptococcus Bovis. 2 presence of echocardiographic evidence of vegetation (which is
oscillating intracardiac mass composed of platelet, fibrin, microorganisms and inflammatory
cells) on valve or supporting structure of valve (papillary muscle or chordate tendineae), or
presence of myocardial abscess or in individuals with prosthetic valve, detachment of the
prosthetic valve from the valve ring is indicative of Infective Endocarditis.

Minor criteria include, 1- predisposing heart condition or injection drug use 2- fever > 38 degree
centigrade 3- presence of vascular phenomena including, major arterial emboli, septic pulmonary
infarct, mycotic aneurysm, intracerebral hemorrhage because of rupture of mycotic aneurysm,
conjunctival hemorrhage or Janeway lesions, 4- presence of immunologic manifestation
including, glomerulonephritis, Osler nodes, Roth spots or elevation of Rheumatoid factor, 5serologic evidence of active infection with organism consistent with Infective Endocarditis.
Diagnosis is made if there are two major criteria, or one major and three minor criteria or if
there are five minor criteria.
Treatment
In individuals with native valve endocarditis since the commonest cause is Streptococcus
species, empiric treatment is two to four weeks course of Penicillin G and Gentamycin, or one
could administer Ceftriaxone + Gentamycin as Ceftriaxone could also cover Staphylococcus (the
second commonest cause of native valve Infective Endocarditis.)
Gentamycin is added because there could be some degree of resistance to PCN or Ceftriaxone
alone and Gentamycin potentiates the effect of PCN or Ceftriaxone.
If culture and susceptibility report is available and if it yields Streptococcus species and if it is
susceptible to PCN, PCN alone without Gentamycin can be continued. If culture demonstrates
the causative organism to be Staphylococcus and if it is susceptible to Naficillin or Ceftriaxone,
Naficillin or Ceftriaxone alone can be continued without Gentamycin.
If culture and susceptibility report is unavailable and if PCN resistant Streptococcus or
Ceftriaxione resistant Staphylococcus is suspected because of poor response, the PCN or
Ceftriaxone is changed to Vancomycin.
In individuals with prosthetic valve endocarditis or in individuals with pacemaker associated
Infective Endocarditis, since the commonest causes are coagulase negative Staphylococcus and
Staphylococcus Aureus, empiric treatment is with:
Naficillin or Oxacillin or Ceftriaxone for 6-8 weeks
+ Gentamycin for 2 weeks
+ Rifampin for 6-8 weeks
Rifampin is added because it can penetrate the biofilm of most of the pathogens that infect
prosthetic valve or other intracardiac devices, for instance pacemaker wire.
If methicillin resistant Staphylococcus is suspected because of poor response, Naficillin,
Oxacillin or Ceftriaxone is changed to Vancomycin to be administered for 6-8 weeks.

In individuals with history of IV drug use, since commonest cause is Staphylococcus, empiric
treatment is 4-6 weeks course of Naficillin and Gentamycin or Ceftriaxone and Gentamycin.
If methicillin resistant Staphylococcus is suspected because of poor response, the Naficillin or
Ceftriaxone is changed to Vancomycin.
Endocarditis due to HACEK organisms is treated with 4 weeks course of Ceftriaxone or with 4
weeks course of Ampicillin and Gentamycin.
If blood culture is available and if it yields a fungal pathogen, for instance in an individual with
prosthetic valve or in an individual with history of IV drug use, antifungal agents are generally
not effective in eliminating fungal Infective Endocarditis, except in Infective Endocarditis caused
by Histoplasma Capsulatum, therefore in individuals with Infective Endocarditis due to Candida
or Aspergillus species, surgical excision of the involved valve, prosthetic valve replacement and
treatment with Amphoterecin B is indicated.
Other indications for cardiac surgical intervention in individuals with endocarditis include:
1-to remove large vegetation causing stenosis of the affected valve
2-and if there is severe valve regurgitation due to the infectious process causing valve
destruction, one need to do valve repair or one may need to excise the infected valve and implant
prosthetic valve.
3-other indication for surgery is presence of perivalvular abscess and/or intracardiac fistula, in
individuals with perivalvular abscess, one need to surgically drain the abscess, and if there is
intracardiac fistula one need to repair the fistula.
4-and in individuals with prosthetic valve, if the prosthetic valve is detached from the valve ring
and unstable, one need to replace the prosthetic valve.