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alternate site of care and specialty pharmacy distribution.
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Infective Endocarditis
Endocarditis is an infection of the
endocardium, the tissue that lines
the inside of the heart’s chambers
and valves. While rare — there are
an estimated 10 cases per 100,000
people each year — endocarditis is
a medical emergency.1 It is difficult
to treat, with death the outcome
in approximately 20% of cases.1
Endocarditis can occur at any
age, but is most commonly seen
in persons over 50 years of age.
The infection can be caused by
bacteria or fungi, although fungal
endocarditis is even less common
than the bacterial kind. The role of
viruses as a cause of endocarditis
is unclear.
consequences of a stroke. In fact,
emboli to the brain, lung, or spleen
occur in 30% of patients and are
often the presenting sign.2
Infective endocarditis (IE) develops
after nosocomial or spontaneous
introduction of bacteria into the
bloodstream that flows to the
surface of the heart valves. This
environment, given its lack of
dedicated microvasculature, allows
bacteria to grow. The organisms
adhere to the valves (vegetation)
and, if left untreated, may
eventually destroy the valves,
ultimately resulting in heart failure.
If bacterial emboli break off from
the vegetation site, they may
cause blockage and mimic the
Damage to the native heart valves
can be due to disease states such
as rheumatic valvular disease,
congenital heart disease that affects
valvular flow, mitral valve prolapse
with an associated murmur, and
degenerative heart disease.
C O N T I N U I N G
Risk Factors
Risk factors for IE include native
heart valve disease, the presence of
a prosthetic heart valve, intravenous
drug abuse, and a recent history
of invasive procedures. Invasive
procedures can include placement
of a cardiac device or central
venous access, surgery, and
dental procedures. Patients who
are immunocompromised are
particularly at risk.
Numbers of valve replacement
procedures continue to rise as
our population ages. Each type
of prosthetic valve has its own
risk/benefit profile. Placement of
any mechanical device presents
a risk of thromboembolism and
E D U C A T I O N
P R O G R A M
requires chronic anticoagulation.
A bioprosthesis, such as a porcine
valve, will eventually deteriorate
and require replacement. Additional
host factors also impact the
decision regarding which type of
valve to use.
Early post-valve endocarditis (PVE)
is typically due to contamination
during valve placement. Late PVE
(after 60 days) is more likely to
be from hematogenous bacterial
spread. Each is distinguished
by its own likely pathogens
and outcomes.
Signs and
Symptoms
The clinical picture of IE is variable,
depending on factors such as the
causative organism, whether a
native or prosthetic valve is used,
comorbidities including cardiac
disease, and other risk factors. Signs
and symptoms also vary depending
on its classification as acute or
subacute IE.
An acute IE infection progresses
rapidly and patients present
with chills, fever, myalgias, and
Table 1: Duke Criteria
3,4
Major Criteria
Minor Criteria
ƒƒ Positive blood cultures
ƒƒ The presence of a
predisposing condition
• A positive result from two
separate blood cultures for a
micro-organism that typically
causes infective endocarditis.
• Persistently positive blood
cultures for 1 of the above
organisms from cultures drawn
more than 12 hours apart.
• Three or more separate
blood cultures drawn at least
1 hour apart.
ƒƒ Echocardiographic evidence of
endocardial involvement
•
Definitive vegetation, myocardial
abscess, or new partial
dehiscence of a prosthetic valve
ƒƒ Development of a new
regurgitant murmur
arthralgias. Subacute infection has
an insidious onset, often developing
over weeks to months. Patients
typically present with vague flulike symptoms. Subacute IE is
more common in a patient with
an underlying valve or congenital
heart defect.
The vast majority of patients with
IE present with fever and heart
murmurs. While less common
today, embolic phenomena such
as splinter hemorrhages, Roth
spots, glomerulonephritis, Osler’s
2 ƒƒ Temperature exceeding
100.4°F (38°C)
ƒƒ Vascular phenomena:
major arterial emboli, septic
pulmonary infarcts,
mycotic aneurysm, intracranial
hemorrhage, conjunctival
hemorrhages, and Janeway
lesions
ƒƒ The presence of immunologic
phenomena (such as
glomerulonephritis, Osler’s
nodes, Roth spots, or
rheumatoid factor)
nodes, and Janeway lesions may
present. Transient petechiae are
commonly seen on the soft palate,
buccal
mucosa,
conjunctiva,
and skin. Ring abscesses are
the pathological hallmark of
mechanical valve PVE.
likely show a decreased serum
hemoglobin, and microscopic
hematuria. While typically present
with IE, these findings are common
with many infectious episodes
and are therefore not specific
to endocarditis.
Diagnosis
An echocardiogram is critical,
particularly in patients who present
with a clinical picture of IE but have
nondiagnostic blood cultures. An
echocardiogram can also help
predict potential complications of
IE, especially those that are embolic
Laboratory studies will likely
show elevated levels of white
cells and C-reactive proteins, as
well as an increased erythrocyte
sedimentation rate. They will also
VOLUME 14
in nature. The echocardiogram
can identify and measure bacterial
vegetation and determine if the
vegetation is mobile or fixed.
It is recommended that the
echocardiogram be performed
as soon as possible — ideally
within 24 hours — in all patients
with suspected IE.2 Transthoracic
echocardiography
(TTE)
or
transesophageal echocardiography
(TEE) may be the imaging method
of choice.
Continuous, versus intermittent,
bacteremia is a hallmark of IE.
The widely used Duke Criteria for
diagnosis (see Table 1) recommends
repeated blood cultures over a
12-hour period prior to starting
antibiotic therapy. However, given
the improvement in outcomes
when therapy is not delayed, more
recent recommendations require
two blood cultures at different
times within a 1-hour period prior to
initiating empiric therapy.2 Positive
results from only 1 set of several
blood cultures should be interpreted
with caution.2
Using the Duke Criteria, a diagnosis
of IE can be made if the patient has
either pathological evidence of IE
(positive microorganisms by culture
or histology) or meets the clinical
criteria (2 major criteria, 1 major and
3 minor, or 5 minor). See Table 1.
According to the Duke criteria,
findings that are consistent with
IE, yet not definitive, indicate a
possible
IE
infection.
The
diagnosis of IE is rejected if: a firm
alternative diagnosis is made; the
IE manifestations resolve within
<4 days of the start of antimicrobial
therapy; or there is no pathologic
evidence of IE at surgery or autopsy
after <4 days of antimicrobial
therapy.3,4
Treatment
Antibiotic treatment is required.
The type of antibiotic used depends
on multiple factors, including
the causative organism and its
susceptibilities,
whether
the
infected valve is native or prosthetic,
and patient-specific variables such
as renal function, drug allergies, and
response to therapy. Given that the
most common causative organisms
for IE include Staphylococcus
aureus, Streptococcus viridans, and
enterococci, empiric therapy should
cover these pathogens, with a
switch to another antibiotic if
necessary when the culture and
sensitivities results are available.
Eradicating bacteria from the fibrinplatelet thrombus is difficult. Due
to the high concentration of
organisms within the vegetation
and the depth of the bacteria
within the thrombus, bactericidal
antibiotics are necessary, typically
for 2 to 6 weeks. For example,
4 weeks of vancomycin is
recommended for staphylococcal
native valve endocarditis (NVE),
lengthened to 6 weeks or longer
with
intracardiac
prostheses,
concomitant lung abscess, or
osteomyelitis. Daptomycin, with
its more rapid bactericidal activity,
may be prescribed for right-sided
endocarditis, particularly if the
patient is intolerant of vancomycin.
Routine switch to oral antimicrobials
is not recommended.2
Surgery is a common requirement
in the attempt to cure IE and should
be addressed early. Typically used to
repair damage to the heart, surgical
intervention may be required in the
presence of life-threatening heart
failure due to surgically treatable
valvular heart disease, persistent
C O N T I N U I N G E D U C AT I O N sepsis, recurrent emboli, metastatic
infection, valvular obstruction, an
abscess or fistula in the heart, or
large vegetation.
Patients who undergo surgery on
an infected valve within 48 hours
of diagnosis have a significantly
better prognosis, primarily due
to the resulting decreased risk of
systemic embolism.5 Similarly, early
device removal in patients with
an infected implantable cardiac
device is associated with improved
1-year survival.1
Prognosis
While much has improved in
terms of medical and surgical
therapies, IE is associated with poor
prognosis
and
remains
a
therapeutic challenge. Outcomes
are significantly influenced by
the causative organisms and
other factors, as described
above. In addition, time to
diagnosis, risk stratification, and
antibiotic administration, as well
as new surgical techniques and
appropriate
follow-up,
are
increasingly recognized as having a
critical impact on outcomes.6
Prevention
Prophylactic
protocols
have
changed significantly since 2008.
Recognizing that the benefits
of prophylactic antibiotics for
routine invasive procedures such
as dental treatments, childbirth,
or bronchoscopy are outweighed
by both side effects and the risk of
developing resistance, prophylaxis
is limited to those patients and
procedures
associated
with
greatest risk.
3
Table 2: High-risk Cardiac Conditions7
ƒƒ Prosthetic cardiac valve
ƒƒ History of infective endocarditis
ƒƒ Congenital heart disease (CHD)
• Unrepaired cyanotic CHD, including palliative shunts and conduits
• Completely repaired congenital heart defect with prosthetic material or device,
whether placed by surgery or by catheter intervention, during the first
6 months after the procedure
• Repaired CHD with residual defects at the site of, or adjacent to the site of,
a prosthetic patch or prosthetic device (which inhibits endothelialization)
ƒƒ Cardiac transplantation recipients with cardiac valvular disease
Guidelines for IE prophylaxis have
been established by the American
Heart Association and are directed
at those patients at significant
risk for IE. (See Table 2.) Singledose antibiotics administered
prophylactically 1 hour prior to the
procedures are recommended for:7
ƒƒ All dental procedures that
involve manipulation of gingival
tissue or periapical region of
teeth or perforation of the oral
mucosa.
ƒƒ Invasive respiratory tract
procedures that involve incision
or biopsy of the respiratory
mucosa (such as tonsillectomy
or adenoidectomy). For invasive
respiratory tract procedures to
treat an established infection
(such as drainage of an abscess),
an antibiotic active against
Stretpococcus viridans should be
administered.
ƒƒ Surgical procedures that involve
infected skin, skin structure,
or musculoskeletal tissue. For
4 these procedures, an antibiotic
should be used that is active
against staphylococci and betahemolytic streptococci.
Alternate Site
of Care
As with many disease states, it
is incumbent upon healthcare
clinicians to consider the most
appropriate site of care. Certainly,
avoiding unnecessary hospital
days decreases costs and reduces
the opportunity for exposure
to nosocomial (often resistant)
pathogens.
Hospital-acquired
infections have been associated
with poorer outcomes in NVE, PVE,
and cardiac device-related IE.1 Given
appropriate candidacy and a process
that ensures effective protocols and
procedures for administration and
monitoring, outpatient therapy
— including in the home — is an
appropriate method for managing
selected patients with IE.2,8
To be appropriate for outpatient
therapy from a clinical perspective,
patients need to be stable and
responding well to therapy and
without signs of heart failure,
indications
for
surgery,
or
uncontrolled extracardiac infection.
Patients with recent valve surgery
for IE who remain hospitalized
solely for completion of therapy
can be considered for home/
outpatient therapy. According to
treatment guidelines, antibiotics
such as ceftriaxone, daptomycin
or teicoplanin that can be given
once per day are suitable agents.
Daptomycin or teicoplanin have
the advantage of administration
via IV push, thus potentially
eliminating the need for a central
line. Other agents can be used
depending on patient and
caregiver
capability.
Careful
monitoring for adverse effects
and
response
to
therapy
are essential.2
VOLUME 14
References
1. Athan E, Chu VH, Tattevin P, SeltonSuty C, Jones P, Naber C, et al. Clinical
characteristics and outcome of infective
endocarditis involving implantable
cardiac devices. JAMA. 2012 Apr; 307(16).
http://jama.jamanetwork.com/article.
aspx?article=1148195. Accessed June
28, 2012.
2. Gould FK, Denning DW, Elliott TSJ,
Foweraker J, Perry JD, Prendergast BD, et
al. Guidelines for diagnosis and antibiotic
treatment of endocarditis in adults: a report
of the working party of the British Society
for Antimicrobial Therapy.
J Antimicrob Chemother. 2012;67(2):
269-289.
3. Tierney LM Jr, McPhee SJ, Papadakis MA,
eds. Infective endocarditis. Current Medical
Diagnosis & Treatment. 38th ed. Stamford,
Conn: Appleton & Lange, 1999:1303-1308.
4. Li JS, Sexton DJ, Mick N, Nettles R, Fowler
VG Jr, Ryan T, Bashore T, Corey GR. Proposed
modifications to the Duke criteria for the
diagnosis of infective endocarditis. Clin
Infect Dis. 2000;30:
633-638.
5. Kang DH, Kim JY, Kim SH, Sun BJ, Kim
DH, Yun SC, et. al. Early surgery versus
conventional treatment for infective
endocarditis. N Eng J Med. 2012;366:
2466-2473.
6. Thuny F, Grisoli D, Collart F, Habib G, Raoult
D. Management of infective endocarditis:
challenges and perspectives. Lancet. 2012
Mar 10;379(9819):965-975. Epub 2012 Feb 7.
www.ncbi.nlm.nih.gov/pubmed/22317840.
Accessed June
28, 2012.
7. Windle ML. Antibiotic prophylactic
regimens for endocarditis. http://
emedicine.medscape.com/article/1672902overview#showall. Updated May 31, 2011.
Accessed June 28, 2012.
8. Partridge DG, O’Brien E, Chapman ALN.
Outpatient parenteral antibiotic therapy for
infective endocarditis: a review of 4 years’
experience at a UK centre. Postgraduate
Med J. 2012 Jul;88(1041):
377-381.
* Do not use the information in this article to
diagnose or treat a health problem or disease
without consulting a qualified physician. Patients
should consult their physician before starting
any course of treatment or supplementation,
particularly if they are currently under medical care,
and should never disregard medical advice or delay
in seeking it because of something set forth in this
publication.
C O N T I N U I N G E D U C AT I O N 5
CORAM’S
V O LU M E 1 4
Coram LLC is a leading national provider of home infusion services, including
alternate site of care and specialty pharmacy distribution.
12450 East Arapahoe Road, Suite A, Centennial, CO 80112 • 720.568.3436
For the branch nearest you, visit coramhc.com.
Infective Endocarditis
SELF-ASSESSMENT QUESTIONS
LEARNING GOAL
To understand the clinical
complexities and treatment options
for bacterial endocarditis.
LEARNING OBJECTIVES
Upon completion of this continuing
education program, the reader will be
able to:
1. Describe the pathophysiology
of and risk factors associated
with bacterial endocarditis.
2. Discuss diagnostic studies and
parameters used to diagnose
endocarditis.
3. Discuss rationale for treatment
strategies.
To obtain two (2.0) contact
hours toward CE credit, please
circle the correct answer (on
the back) for each question and
forward to:
Coram’s Healthline
Coram Specialty Infusion Services
12450 East Arapahoe Rd, Suite A
Centennial, CO 80112
Please allow approximately 7
days to process your test and receive the certificate upon achieving a passing score.
C O N T I N U I N G
Please circle the correct answer for
each question. The passing score for
this test is 100%.
1. Emboli are a significant potential
consequence of IE.
a. True
b.False
2. Risk factors for IE include:
a. Clinical conditions associated
with native heart valve
disease
b.The presence of a prosthetic
heart valve
c. Intravenous drug abuse
d.Recent history of invasive
procedures
e.A and B
f. All of the above
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E D U C A T I O N
P R O G R A M
3. Early post-valve endocarditis
(PVE) is typically hospitalacquired.
a. True
b.False
4. A patient with a valvular defect is
most likely to develop an acute IE.
a. True
b.False
5. Invasive procedures that can
place a patient at risk for IE
include:
a. Placement of a cardiac device
b.Placement of a central
venous access
c. Dental procedures
d.A and C
e.All of the above
6. The following statements
regarding echocardiogram are
true EXCEPT:
a. It is performed only when
blood cultures have proven
nondiagnostic.
b.It can help identify bacterial
vegetation.
c. It can measure bacterial
vegetation.
d.It should ideally be
performed within 24 hours
when IE is suspected.
7. A positive blood culture
indicates IE.
a. True
b.False
8. Two weeks of oral antibiotics
is the initial protocol for the
treatment of IE.
a. True
b.False

9. Patients who undergo surgery
on an infected valve within
48 hours of diagnosis have a
minimally improved prognosis.
a. True
b.False
10. Prophylactic antibiotics are
currently recommended
only for high-risk patients
undergoing certain invasive
procedures.
a. True
b.False
PLEASE CUT OFF BOTTOM PORTION
ANSWERS
Volume 14: Infective Endocarditis
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