Infective Endocarditis

Basic Information
• Infective endocarditis refers to infection of the endocardium and most commonly refers to infection
of one of the heart valves
o Infective endocarditis may present acutely with devastating consequences or be slowly
progressive and have subtle clinical findings
o Bacterial and fungal organisms may cause infective endocarditis
o Noninfective endocarditis may be caused by inflammatory conditions of the endocardium
and valves (e.g., Libman-Sacks endocarditis associated with systemic lupus erythematosus)
• Types of infective endocarditis
o Native valve endocarditis, acute and subacute
o Prosthetic valve endocarditis, early and late
o Intravenous drug use-related endocarditis
• The classic clinical presentation and course of infective endocarditis have been historically
characterized as either acute or subacute
o Acute native valve endocarditis is usually aggressive and is typically caused by virulent
organisms, e.g., Staphylococcus aureus and group B streptococci.
o Subacute native valve endocarditis typically affects abnormal valves. It is often an indolent
infection and is more commonly caused by organisms such as the viridans group streptococci
▪ In subacute bacterial endocarditis, left-sided valvular infection is more common than
right- sided valvular infection. Tricuspid valve involvement is much less common.
Infection of the pulmonic valve is rare
o The increasing prevalence of prosthetic heart valves, along with the evolving infectious
etiologies of endocarditis, have made the acute versus subacute distinction less clinically
useful
▪ Because the etiologic agent is what determines treatment, infective endocarditis is
now classified by organism, rather than the time course of the infection
• Predisposing factors
o Age older than 60 years
o Male sex
o Abnormal cardiac anatomy
▪ Having an abnormal native heart valve is the most common predisposing factor
▪ Mitral valve prolapse is among the most common associated abnormalities (20% to
30% of cases); the presence of a murmur or thickened valve associated with highest
risk
▪ Rheumatic heart disease becoming less common in developed nations
▪ Bicuspid aortic valves can be seen as a predisposing factor
▪ Congenital heart disease, including atrial and ventricular septal defects and patent
ductus arteriosus
▪ Presence of prosthetic valves
o Injection drug use
o Poor dentition
o Presence of an intravascular device, such as a catheter
o Previous endocarditis
o Hemodialysis
o HIV infection

Clinical Presentation
• Signs and symptoms
o Symptoms are often nonspecific and include fever, malaise, chest pain, night sweats
o Cardiac findings that may be seen include new murmurs, vegetations on echocardiography
(absence of a visible vegetation does not exclude diagnosis), conduction abnormalities
(especially with endocarditis of aortic valve), and congestive heart failure
o Cough, pleurisy, and cavitating pulmonary infiltrates can be seen in right-sided endocarditis
o Signs of systemic inflammation, such as fever, fatigue or failure to thrive, and arthralgias can
be seen
o Systemic emboli are seen in up to 45% of patients; may involve any organ; can lead to renal
infarcts, splenic infarcts, pulmonary embolism, myocardial infarction if central nervous
 system is involved; middle cerebral artery territory is most commonly affected. Large emboli
are more common in fungal endocarditis.
o Mycotic aneurysms are aneurysms associated with infective endocarditis; they usually arise in
the cerebral arteries and aorta, but may also involve other major arteries
o Metastatic infection from bacteremia or fungemia can occur (e.g., vertebral osteomyelitis)
o Immune complex disease more often occurs in patients with subacute bacterial endocarditis;
findings include glomerulonephritis, Roth spots (retinal hemorrhages), and Osler nodes
(tender nodules on finger or toe pads)
o Other: Splinter hemorrhages (especially in proximal nail beds), Janeway lesions (nodular
hemorrhages on palms of hands and soles of feet, caused by microabscesses), petechiae,
splenomegaly, digital clubbing
• Etiologic agents
o Streptococci spp. and staphylococci spp. account for the majority of infective endocarditis,
but a variety of bacteria and fungi may be implicated
▪ Staphylococci spp. account for the majority of cases of health care-associated
infective endocarditis
▪ Staphylococci spp. and streptococci spp. occur in roughly equal proportions in with
community-acquired infective endocarditis
o Viridans group streptococci are the most common streptococci spp.
▪ Pyogenic strep: groups A, C rarely cause endocarditis
▪ Streptococcus gallolyticus subspecies gallolyticus (Streptococcus bovis biotype I):
Associated with gastrointestinal (GI) neoplasms; should prompt evaluation of the
colon for malignancy
▪ Streptococcus mutans: An oral pathogen; may cause endocarditis in the susceptible
host with poor dentition
o S. aureus is the most commonly implicated Staphylococci spp.
▪ S. aureus infective endocarditis may involve normal heart valves and result in rapid
progression with valve destruction. It is the most common cause of acute
endocarditis
o Enterococcus spp. are an increasingly prevalent cause of endocarditis and can be seen in
older men following genitourinary (GU) instrumentation and in women following obstetric
procedures
o Pseudomonas spp.: Very uncommon; typically occurs in those with history of intravenous (IV)
drug use; usually right-sided
o Culture-negative infective endocarditis: May present with endocardial vegetation or embolic
events
▪ HACEK (Haemophilus aphrophilus, Actinobacillus actinomycetemcomitans,
Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae) organisms are
now readily cultured with contemporary blood culture systems; this group accounts
for 3% to 5% of native valve infections
▪ May need to hold blood cultures for 3 weeks if organisms such as Bartonella and
Brucella are suspected
• Unusual infective endocarditis organisms
o Coxiella burnetii (Q fever): Diagnosed by serology; culture often negative
o Fungi: Candida spp. most common, followed by Aspergillus spp.; susceptible hosts include
those with history of injection drug use, prosthetic heart valve recipients, and
immunocompromised hosts
o Bartonella, Chlamydia, Legionella, Brucella, Mycoplasma spp. are rare causes of infective
endocarditis
• Prosthetic valves
o Late prosthetic valve endocarditis occurs 12 months after valve insertion
o The risk of prosthetic valve endocarditis is highest in the first 6 months following valve
placement; infections less than 2 months after surgery are often nosocomial, although those
that occur more than 2 months after surgery are more likely to be community-acquired
o S. aureus and coagulase negative staphylococci spp. are the most common causes of
prosthetic valve endocarditis
o Viridans group streptococci are a rare cause of early prosthetic valve endocarditis, but are a
relatively common cause of late prosthetic valve endocarditis
Diagnosis and Evaluation
• Diagnosing endocarditis requires a high index of suspicion
• Definite bacterial endocarditis is a pathologic diagnosis made by culture cardiac tissue
o Clinical criteria are often used to diagnose endocarditis; typically requires a demonstration of
persistent bacteremia by blood culture with an organism likely to cause endocarditis, along
with echocardiographic and/or clinical findings
▪ Blood cultures: Three separate sets of cultures drawn should be drawn, ideally from
three different sites. They should also be separated in time, ideally 6 hours apart.
▪ Transthoracic echocardiography (TTE): First step in patients with native valves, no
congenital heart disease, and no previous endocarditis; sensitivity is up to 62%. If
intermediate-to-high probability of having endocarditis, proceed to transesophageal
echocardiography (TEE).
▪ TEE: Can consider as a first step in patients with prosthetic valves, congenital heart
disease, and previous endocarditis/valve abnormalities; sometimes a first step in
patients with limited transthoracic windows, clear stigmata of endocarditis, and new
murmurs
• Sensitivity ranges from 90% to 100% in native valve endocarditis, and is
lower in prosthetic valve endocarditis; a negative TEE does not necessarily
rule out infective endocarditis
• Possible endocarditis, in which diagnostic criteria are not met, should be treated as endocarditis until
an alternate diagnosis is confirmed

Treatment
• Treatment principles in endocarditis
o Parenteral antibiotics preferred to ensure consistent and therapeutic antibiotic levels
o Extended therapy indicated—usually 4 to 6 weeks, depending on the etiologic agent (shorter
courses associated with risk of relapse)
o Bactericidal antibiotics are preferred to bacteriostatic antibiotics
▪ Antibiotic choice should be guided by culture and sensitivity results
• When to consider surgery:
o Failure of medical therapy (i.e., persistent bacteremia or fungemia)
o Infection with difficult to treat organisms (e.g., fungal organisms, Pseudomonas spp. or
Brucella spp. endocarditis)
o Major embolic events
o New congestive heart failure; particularly with moderate to severe aortic or mitral
regurgitation
o Significant valve dysfunction, especially in prosthetic valves
o Paravalvular extension; may be manifested by prolonged fever, aortic valve ring abscess,
atrioventricular conduction abnormalities, and/or fistulas and mycotic aneurysms
o Prosthetic valve and organisms such as S. aureus, Pseudomonas spp., fungi, and resistant
enterococci

Prevention of Endocarditis
• Endocarditis prophylaxis
o Endocarditis prophylaxis recommendations were revised in 2007 because the risk of
endocarditis from dental procedures is less than previously estimated
o Prophylaxis should be offered to patients with high-risk cardiac conditions who are
undergoing procedures that are likely to cause bacteremia
o Procedures likely to cause bacteremia include:
▪ Dental procedures that involve manipulation of the gingiva or periapical region of
the teeth, or perforation of the oral mucosa (not routine dental cleaning)
▪ Procedures of the respiratory tract that will lead to an incision or biopsy of the
respiratory mucosa
▪ GI or GU procedures, only in patients with active GI/GU infections
▪ Procedures involving infected skin or musculoskeletal tissue
▪ Cardiac surgery involving placement of prosthetic material
o High-risk cardiac conditions include:
 ▪ Prosthetic cardiac valves, bioprosthetic and homograft
▪ Presence of prosthetic material used for valve repair
▪ Previous infective endocarditis
▪ Unrepaired cyanotic congenital heart disease, including palliative shunts and
conduits
▪ Completely repaired congenital heart defect with prosthetic material or device
during the first 6 months after the procedure
▪ Repaired congenital heart disease with residual defects at the site or next to the
prosthesis
▪ Cardiac transplant recipients who develop cardiac Valvulopathy
o Antibiotic recommendations
▪ Single-dose oral amoxicillin (2 g) 30 to 60 min before procedure (clindamycin,
clarithromycin, or azithromycin if penicillin allergic)
▪ Parenteral alternative: ampicillin 2 g IV or intramuscularly (cefazolin or ceftriaxone 1
g IM or IV are also acceptable)
▪ If patient has a severe penicillin allergy and is unable to take oral medications, a
single dose of clindamycin (600 mg), azithromycin (500 mg), or vancomycin 15 mg/kg
can be used
▪ If biopsy through active infection, consider vancomycin if methicillin-resistant S.
aureus (MRSA) is a concern
o Low-risk patients for whom antibiotic prophylaxis is not recommended
▪ Mitral valve prolapse
▪ Bicuspid aortic valve
▪ Acquired aortic or mitral valve disease
▪ Pacemakers
▪ Defibrillators
o Low-risk procedures for which endocarditis prophylaxis is not recommended:
▪ GI endoscopy (except sclerosis or dilatation/ endoscopic retrograde
cholangiopancreatography)
▪ Restorative dentistry
▪ Gynecologic procedures: vaginal hysterectomy, vaginal delivery, cesarean section
▪ Cardiac procedures: cardiac catheterization, balloon angioplasty