3. Definition
• 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
4. Further Classification
• Acute
– Affects normal heart
valves
– Rapidly destructive
– Metastatic foci
– Commonly Staph.
– If not treated, usually
fatal within 6 weeks
• Subacute
– Often affects damaged
heart valves
– Indolent nature
– If not treated, usually
fatal by one year
5. Pathophysiology
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 endocardial surface
4. Eventual invasion of the valvular leaflets
6. Epidemiology
• Incidence difficult to ascertain and varies according to
location
• Much more common in males than in females
• May occur in persons of any age and increasingly common in
elderly
• Mortality ranges from 20-30%
8. Infecting Organisms
• Common bacteria
– Viridans group streptococci (S. mutans, S. sanguis, S. mitis)
– Staphylococcus aureus
– Group D streptococcus (enterococcus) (S. bovis, S. faecalis)
• Not so common bacteria
– Pseudomonas
– HACEK
• Fungi
9. Symptoms
• Acute
– High grade fever and
chills
– SOB
– Arthralgias/ myalgias
– Abdominal pain
– Pleuritic chest pain
– Back pain
• Subacute
– Low grade fever
– Anorexia
– Weight loss
– Fatigue
– Arthralgias/ myalgias
– Abdominal pain
– N/V
The onset of symptoms is usually ~2 weeks or less
from the initiating bacteremia
10. Signs
• Fever
• Heart murmur( new or changing murmur)
• Nonspecific signs – petechiae, subungal or
“splinter” hemorrhages, clubbing,
splenomegaly, neurologic changes
• More specific signs - Osler’s Nodes, Janeway
lesions, and Roth Spots
11. Petechiae
Photo credit, Josh Fierer, M.D.
medicine.ucsd.edu/clinicalimg/ Eye-Petechiae.html
Harden Library for the Health Sciences
www.lib.uiowa.edu/ hardin/
md/cdc/3184.html
1.Nonspecific
2.Often located on extremities
or mucous membranes
dermatology.about.com/.../
blpetechiaephoto.htm
12. Splinter Hemorrhages
1. Nonspecific
2. Nonblanching
3. Linear reddish-brown lesions found under the nail bed
4. Usually do NOT extend the entire length of the nail
13. Janeway lesions
American College of Rheumatology
webrheum.bham.ac.uk/.../ default/pages/3b5.htm www.meddean.luc.edu/.../
Hand10/Hand10dx.html
1.Erythematous, blanching macules
2.Nonpainful
3.More specific
4.Located on palms and soles
14. Osler’s Nodes
1. More specific
2. Painful and erythematous nodules
3. Located on pulp of fingers and toes
4. More common in subacute IE
15.
16. The Essential Blood Test
• Blood Cultures
– Minimum of three blood cultures1
– Three separate venipuncture sites
– Obtain 10-20mL in adults and 0.5-5mL in children2
• Positive Result
– 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 more positive blood cultures in which the first and last
samples were collected at least one hour apart
18. Imaging
• Chest x-ray
– Look for multiple focal infiltrates and calcification of heart valves
• EKG
– Rarely diagnostic
– Look for evidence of ischemia, conduction delay, and arrhythmias
• Echocardiography
19. 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
20. Modified Duke Criteria
• Definite IE
– Pathologic criteria
• Microorganism: (via culture or histology) in a valvular vegetation,
embolized vegetation, or intracardiac abscess
• Pathological lesions: vegetation or intracardiac abscess present,
confirmed by histology showing active endocarditis
– Clinical criteria
• Two major criteria, or
• One major and three minor criteria, or
• Five minor criteria
21. Con’d
• Possible IE
One major criterion and one minor criterion or three minor
criteria
• Rejected IE
Firm alternative diagnosis for manifestations of endocarditis, or
Sustained resolution of manifestations of endocarditis, with
antibiotic therapy for 4 days or less, or
No pathological evidence of infective endocarditis at surgery or
autopsy, after antibiotic therapy for 4 days or less
22. Con’d
• Major Criteria
Positive blood culture
– Typical microorganism for infective endocarditis from two separate
blood cultures
– Persistently positive blood culture, defined as recovery of a
microorganism consistent with infective endocarditis from:
• Blood cultures (≥2) drawn more than 12 hr apart, or
• All of three or a majority of four or more separate blood
cultures, with first and last drawn at least 1 hr apart
– Single positive blood culture for Coxiella burnetii or antiphase I IgG
antibody titer >1:800
23. Con’d
Evidence of endocardial involvement
– Positive echocardiogram
• Oscillating intracardiac mass, on valve or supporting structures,
or in the path of regurgitant jets, or on implanted material, in
the absence of an alternative anatomical explanation, or
• Abscess, or
• New partial dehiscence of prosthetic valve, or
– New valvular regurgitation (increase or change in preexisting
murmur not sufficient)
24. Con’d
Minor Criteria
– Predisposition: predisposing heart condition or intravenous drug use
– Fever ≥38.0°C (100.4°F)
– Vascular phenomena: major arterial emboli, septic pulmonary
infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival
hemorrhages, Janeway lesions
– Immunological phenomena: glomerulonephritis, Osler nodes, Roth
spots, rheumatoid factor
– Microbiological evidence: positive blood culture but not meeting
major criterion as noted previously[*]
or serologic evidence of active
infection with organism consistent with infective endocarditis
25. Con’d
• The following minor criteria are added to those already listed:
– the presence of newly diagnosed clubbing
– splenomegaly
– splinter hemorrhages, and petechiae
– a high erythrocyte sedimentation rate
– a high C-reactive protein level
– the presence of central nonfeeding lines
– peripheral lines
– microscopic hematuria
26. Treatment
• Parenteral antibiotics
– High serum concentrations to penetrate vegetations
– Prolonged treatment to kill dormant bacteria clustered in vegetations
• Surgery
– Intracardiac complications
– intractable heart failure
– failure to sterilize the blood despite adequate antibiotic levels
– increasing size of vegetations while receiving therapy
• Surveillance blood cultures
27. • Acute endocarditis or prosthetic valvae endocarditis
vancomycin 30mg/kg/day(ceftriaxone 2gm/day) plus gentamycin
3mg/kg/day once daily or in 2-3 divided doses immedietly after blood
culture.
• Subacute endocarditis –if patient hemodynamically stable wait for 2-
3 days till blood culture result.
• Culture positive treat based on the isolated organisms
• Culture is negative endocarditis
• SBE-ceftriaxone 2gm /day+gentamycin 3gm/kg for the 1st
2wks and
continue with ceftriaxone only for the remaining weeks of therapy
• Acute endocarditis –continue vancomycin +gentamycin for 2wks and then
vancomycin for the remaining wks of therapy
• patients with proven or suspected enterococcal endocarditis should
receive combination of vancomycin and gentamycin for the whole
duration of therapy.
• Duration of therapy- 4wks for most patients
28. PREVENTION
• Antimicrobial prophylaxis before various procedures and
other forms of dental manipulation may reduce the
incidence of infective endocarditis in susceptible patients
30. Antibiotic Regimens for Prophylaxis of
Endocarditis in Adults with High-Risk Cardiac
Lesions
31. Complications
• Four etiologies
– Embolic
– Local spread of infection
– Metastatic spread of infection
– Formation of immune complexes – glomerulonephritis and
arthritis
32. Embolic Complications
• Occur in up to 40% of patients with IE
• Predictors of embolization
– Size of vegetation
– Left-sided vegetations
– Fungal pathogens, S. aureus, and Strep. Bovis
• Incidence decreases significantly after
initiation of effective antibiotics
33. Embolic Complications
• Stroke
• Myocardial Infarction
– Fragments of valvular vegetation or vegetation-
induced stenosis of coronary ostia
• Ischemic limbs
• Hypoxia from pulmonary emboli
• Abdominal pain (splenic or renal infarction)
36. Local Spread of Infection
• Heart failure
– Extensive valvular damage
• Paravalvular abscess (30-40%)
– Most common in aortic valve, IVDA, and S. aureus
– May extend into adjacent conduction tissue causing
arrythmias
– Higher rates of embolization and mortality
• Pericarditis
• Fistulous intracardiac connections
37. 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.
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.
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.
