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IE often occurs when there is an underlying cardiac abnormality that creates a high-low pressure gradient. The resultant turbulent blood flow disrupts the endocardial surface by peeling away the endothelium. The body’s natural response to endothelial damage is to repair it by laying down a sticky platelet-fibrin meshwork, which is a nidus for infection. Temporary bacteremia delivers the offending organism to the endocardial surface where is sticks to the platelet-fibrin meshwork. This festers into an infection that eventually invades the cardiac valves. The pathophysiology is slightly different with IVDA. It has been postulated that repeated injections of drugs and particulate material causes microtrauma to the cardiac valves, thereby starting the infection cascade.
There is an estimated 10-15,000 new cases of IE diagnosed in the U.S. each year, although the exact incidence of IE is difficult to ascertain. IE is a relatively uncommon disease, is not a reportable disease, and different case definitions have existed throughout the years. Furthermore, the incidence varies greatly depending on geographic regions. IE is more common among males. The male:female ratio varies from 2:1 to 9:1 depending on the source. In the past, IE was a disease of children and young adults. It predominantly affected children with congenital heart disease and adults with rheumatic heart disease. Today, IE commonly affects the elderly, with almost 50% of cases in the U.S. occurring in patients over the age of 60. This may be due to the decreasing incidence of rheumatic heart disease and the increasing proportion of elderly in the U.S. Mortality from IE remains high, and ranges from 20-30% despite newer antibiotics and surgical options.
The top three risk factors for IE include, IVDA, prosthetic heart valves, and structural heart disease. IVDA – one large study of IVDAs found that the use of cocaine was associated with a higher risk of IE than other injectable drugs. The most significant risk factor for right-sided IE is IVDA, although left sided disease is quite common among IVDAs. The most common infecting organism is clearly S. aureus, particularly in right-sided infection. Prosthetic valve IE comprises a small proportion of all cases of IE and occurs in only 1% of all patients with artificial heart valves. The greatest risk is in the first year following valve replacement. Structural heart disease – approximately ¾ of all cases of IE occur in patients with preexisting structural heart abnormalities. The most common underlying heart abnormalities include mitral valve prolapse with mitral regurgitation and aortic stenosis. The most common congenital heart defects include Tetralogy of Fallot, bicuspid aortic valves, coarctation of the aorta, VSDs, and patent ductus arteriosus. In general, the higher the gradient of the valvular insufficiency, the higher the risk of IE. One of the greatest risk factors of all is a prior episode of IE. Some studies have documented recurrence as high as 9%.
Staphlococcal and Streptococcal organisms comprise over 80% of all infecting organisms.
Subungal hemorrhages that extend the entire length of the nail or are primarily located at the proximal end of the nail (near the cuticle) are like due to trauma.
If you suspect the pt has subacute IE or is not critically ill, then the three samples can be collected over 24-72 hours and antibiotics can be held until all three samples have been drawn. However, if the pt is acutely ill, critical, or unstable, the three cultures should be obtained over a 1 hour time span before beginning empiric therapy. There is no need to collect anaerobic blood cultures since virtually all cases of IE are caused by aerobic organisms. There is little additional diagnostic yield to collecting more than three blood cultures unless the pt was previously on antibiotics. In one study of 206 cases of IE, the initial blood culture was positive in 96% of streptococcal IE and one of the first two cultures were positive 98% of the time. For pt’s with IE cause by organisms other than strep, one of the first two blood culture was positive in 100% of the cases. The estimated diagnostic yield of a blood culture increases by about 3% per mL of blood cultured. One study found that the detection rate for bacteremia increased from 69% to 92% when at least 5mL of blood were used for culture. The most common cause of negative cultures in patients with IE is prior antibiotic use.
CBC – Look for a normochromic normocytic anemia and/or a leukocytosis. ESR and CRP - Look for an elevated erythrocyte sedimentation rate and/or an elevated C-reactive protein which are present 90-100% of the time. RF - Occasionally there will be an elevated levels of Rheumetoid Factor, particularly in patients who have been infected for six weeks or more. (Minor Duke’s Criteria) UA - Urinalysis may reveal microscopic or gross hematuria, proteinuria, and pyuria. These findings along with a low serum complement level indicate a glomerulonephritis or “immunologic phenomena”. (Minor Duke’s Criteria)
CXR – A chest xray can contain multiple diagnostic clues such as calcification of heart valves, which should raise suspicion in a febrile patient without an obvious source. More commonly, the chest xray may reveal septic pulmonary emboli in a patient with right-sided IE (Minor Duke’s Criteria). EKG – An EKG alone cannot diagnose IE but it may show evidence of some of the disease’s complications. For example, EKG with ST changes may indicate ischemia or infarction from septic emboli. Arrhythmias such as heart block may indicated extension of the infection from the valves into the septum and surrounding cardiac tissue.
TTE and TEE are complementary for evaluating cardiac hemodynamics and anatomy, but TEE has superior sensitivity, especially in detecting native valve vegetations, prosthetic valve vegetations, and local extension of infection. However, it is significantly more expensive and invasive. If there is any suspicion of IE, get a TTE. If there is staph or fungal bacteremia, a TEE should probably be obtained. If there is a high clinical suspicion for IE and the TTE is negative, you should proceed to a TEE. If there is a concern for intracardiac complications, a TEE is warranted. It’s important to remember that the negative predictive value of a TEE is between 96-98%, meaning that a TEE cannot definitively rule out endocarditis. If the initial TEE is negative in a patient with a high clinical suspicion for IE, a repeat examiniation should be done if the pt does not improve.
Pelletier and Petersdorf criteria – 3 case categories: Definite – histologic evidence of endocardial vegetations on examination of tissue Probable - uniformly positive blood cultures with know underlying heart disease or embolic phenomena OR negative blood cultures in pts with fever, new regurgitant valvular heart murmur, and embolic phenomena Possible - uniformly positive blood cultures with know underlying heart disease or embolic phenomena OR negative blood cultures with fever and known underlying heart disease and embolic phenomena Von Reyn criteria – modified the above criteria to improve specificity and clinical utility. Duke Criteria – relies upon major and minor clinical and pathologic criteria to classify cases as definite, possible, and rejected
Multiple studies have validated the Duke criteria. When applied and reapplied over the entire evaluation, these criteria are sensitive and specific and very rarely erroneously reject a true endocarditis.
Systemic emboli are among the most common complications of IE, occurring in up to 40% of patients. Subclinical emboli are often found on autopsy.
DR MOHAMMAD ALI KHALID,
Assistant professor of medicine,
RMC and allied teaching hospitals.
Infectious Endocarditis (IE): an infection of
the heart’s endocardial surface
Classified into four groups:
– Native Valve IE
– Prosthetic Valve IE
– Intravenous drug abuse (IVDA) IE
– Nosocomial IE
Worsening of valve dysfunction.
Vegetations seen on echocardiography.
Positive blood cultures.
– Affects normal heart
– Rapidly destructive
– Metastatic foci
– Commonly Staph.
– If not treated, usually
fatal within 6 weeks
– Often affects damaged
– Indolent nature
– If not treated, usually
fatal by one year
1. Turbulent blood flow disrupts the
endocardium making it “sticky”
2. Bacteremia delivers the organisms to
the endocardial surface
3. Adherence of the organisms to the
4. Eventual invasion of the valvular
Incidence difficult to ascertain and varies
according to location
Much more common in males than in
May occur in persons of any age and
increasingly common in elderly
Mortality ranges from 20-30%
Intravenous drug abuse
Artificial heart valves and pacemakers
Acquired heart defects
– Calcific aortic stenosis
– Mitral valve prolapse with regurgitation
Congenital heart defects
– S. aureus
Not so common bacteria
– High grade fever and
– Arthralgias/ myalgias
– Abdominal pain
– Pleuritic chest pain
– Back pain
Low grade fever
The onset of symptoms is usually ~2 weeks or less
from the initiating bacteremia
Valve surgery or repair
Nonspecific signs – petechiae, subungal
or “splinter” hemorrhages, clubbing,
splenomegaly, neurologic changes.
More specific signs - Osler’s Nodes,
Janeway lesions, and Roth Spots.
Features particular to a specific valve.
2. Often located on extremities
or mucous membranes
Photo credit, Josh Fierer, M.D.
Harden Library for the Health Sciences
3. Linear reddish-brown lesions found under the nail bed
4. Usually do NOT extend the entire length of the nail
American College of Rheumatology
1. More specific
2. Painful and erythematous nodules
3. Located on pulp of fingers and toes
4. More common in subacute IE
1. More specific
2. Erythematous, blanching macules
4. Located on palms and soles
The Essential Blood Test
Minimum of three blood cultures1
Three separate venipuncture sites
Obtain 10-20mL in adults and 0.5-5mL in children2
– Typical organisms present in at least 2 separate samples
– Persistently positive blood culture (atypical organisms)
Two positive blood cultures obtained at least 12 hours apart
Three or a more positive blood cultures in which the first and
last samples were collected at least one hour apart
– Look for multiple focal infiltrates and
calcification of heart valves
– Rarely diagnostic
– Look for evidence of ischemia, conduction
delay, and arrhythmias
Indications for Echocardiography
Transthoracic echocardiography (TTE)
– First line if suspected IE
– Native valves
Transesophageal echocardiography (TEE)
– Prosthetic valves
– Intracardiac complications
– Inadequate TTE
– Fungal or S. aureus or bacteremia
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”
IV drug abuser
Minor echo findings(eg
deformed valve but no
Vascular embolic events
like janeway lesions
septic pul infarcts
Modified Duke Criteria
– Microorganism (via culture or histology) in a valvular vegetation,
embolized vegetation, or intracardiac abscess
– Histologic evidence of vegetation or intracardiac abscess
1 major and 3 minor
– Resolution of illness with four days or less of antibiotics
– High serum concentrations to penetrate
– Prolonged treatment to kill dormant bacteria
clustered in vegetations
– Intracardiac complications
Surveillance blood cultures
1mg/kg QID 2 wks
max upto 4 wks.
oral for four days
Liver and kidneys
Valve replacement mandatory after 2wks
therapy with amphoterecin therapy.
Monitor drug levels according to
– Local spread of infection
– Metastatic spread of infection
– Formation of immune complexes –
glomerulonephritis and arthritis
Occur in up to 40% of patients with IE
Predictors of embolization
– Size of vegetation
– Left-sided vegetations
– Fungal pathogens, S. aureus, and Strep.
Incidence decreases significantly after
initiation of effective antibiotics
– Fragments of valvular vegetation or
vegetation-induced stenosis of coronary ostia
Hypoxia from pulmonary emboli
Abdominal pain (splenic or renal
Local Spread of Infection
– Extensive valvular damage
Paravalvular abscess (30-40%)
– Most common in aortic valve, IVDA, and S. aureus
– May extend into adjacent conduction tissue causing
– Higher rates of embolization and mortality
Fistulous intracardiac connections
Local Spread of Infection
Acute S. aureus IE with perforation of the
aortic valve and aortic valve vegetations.
Acute S. aureus IE with mitral valve ring
abscess extending into myocardium.
Poor Prognostic Factors
Low serum albumen
Apache II score
Amoxicillin 2gm oral 1 hr
before.Clindamycin 600mg or
clarithromycin500mg if allergic to
Ampicillin 2gm +Gentamycin
1mg/kg within ½ hr of starting IV
followed byAmpicillin 1gm IV 6 hrs