Infective Endocarditis

INFECTIVE ENDOCARDITIS
Brook A. July/2016
Harrison’s 19th ed.; Nelson’s 18th;
Braunwald 10th ed.
INTRODUCTION
 The prototypic lesion of infective endocarditis, the
vegetation, is a mass of platelets, fibrin, microcolonies
of microorganisms, and scant inflammatory cells.
 Infections most commonly involve the heart valve
(high pressure area), either native or prosthetic b
 Infection most commonly involves
 Heart valves (either native or prosthetic)
 Low-pressure side of a ventricular septal defect,
 On the mural endocardium where it is damaged by aberrant
jets of blood or foreign bodies, or
 On intracardiac devices themselves.
The analogous process involving arteriovenous shunts,

arterioarterial shunts (PDA), or a coarctation of the aorta is called
infective endarteritis.
INTRODUCTION
 The analogous process involving arteriovenous
shunts, arterioarterial shunts (patent ductus
arteriosus), or a coarctation of the aorta is
called infective endarteritis.
 Endocarditis may be classified according to the

temporal evolution of disease, the site of
infection, the cause of infection, or a
predisposing risk factor such as injection drug
use.
TYPES
 While each classification criterion provides
therapeutic and prognostic insight, none is
sufficient alone.
 Acute endocarditis is a hectically febrile illness that
rapidly damages cardiac structures, hematogenously
seeds extracardiac sites, and, if untreated,
progresses to death within weeks.
 Subacute endocarditis follows an indolent course;

causes structural cardiac damage only slowly, if at
all; rarely metastasizes; and is gradually progressive
unless complicated by a major embolic event or
ruptured mycotic aneurysm
EPIDEMIOLOGY
 In developed countries, the incidence of
endocarditis ranges from 2.6 to 7 cases per
100,000 population per year and has remained
relatively stable during recent decades.
 In these countries, predisposing factors are

shifting to illicit IV drug use, degenerative valve
disease, and intracardiac devices.
EPIDEMIOLOGY
 The incidence of endocarditis is notably
increased among the elderly.
 30–35% of cases of native valve endocarditis

(NVE) are associated with health care
 16–30% of all cases of endocarditis involve

prosthetic valves.
 The risk is greatest during the first 6–12 months
after valve replacement; gradually declines to a
low, stable rate thereafter; and is similar for
mechanical and bioprosthetic devices
MICROBIOLOGY
 Although many species of bacteria and fungi
cause sporadic episodes of endocarditis, a few
bacterial species cause the majority of cases.
 The overall distribution of infecting organisms

has remained the same, with gram-positive cocci
being predominant.
 These include streptococcal, staphylococcal, and
enterococcal species.
 The modified Duke criteria listed only these three
groups of pathogens as “typical microorganisms”
MICROBIOLOGY
 Streptococcal spp- Viridans Strept
 Among these, viridans group streptococci, are the most
important causes
 These organisms normally are found in the mouth of humans
and tend to cause indolent infections
 The viridians group includes several evolving species of

streptococci and currently includes sanguis, oralis
(mitis), salivarius, mutans, intermedius, anginosus, and
constellatus
 The latter three species have been referred to the S.
anginosus or S. milleri group
 These are unique in that they have a proclivity to produce
abscess formation and metastatic infection foci, both within

the heart and in extracardiac locations in patients with IE.
MICROBIOLOGY
 The viridans group streptococci also include species
of Gemella, Abiotrophia, and Granulicatella.
 For Gemella, one species designated as morbillorum

used to be listed in the Streptococcus genus.
 These organisms can cause IE and exhibit metabolic

characteristics akin to those of the “nutritionally
variant streptococci,” which have now been
reassigned to the Abiotrophia and Granulicatella
genera.
MICROBIOLOGY
 Viridansgroup streptococci constitute the
predominant cause of native valve infection acquired in
the community setting, in both developing and
developed nations.
 Similarto other bacteria, viridans group streptococci

have developed resistance to some antibiotics.
 Fortunately, resistance to penicillin is seen in a minority of IE
isolates.
 Resistance is not based on beta-lactamase production, and
the definitions used to characterize strains as being

7
penicillin-resistant are not the same as the breakpoints

recommended by the Clinical and Laboratory Standards
Institute (CLSI).
MICROBIOLOGY
 Streptococcal spp- Beta-hemolytic Strept
 Beta-hemolytic streptococci typically cause an acute
presentation of IE.
 Injection drug users and elderly persons are two at-

risk groups.
 Complications are frequent and often involve valve

destruction and distant sites, often musculoskeletal, of
infection.
 The prevalence of beta-hemolytic streptococci among

cases of IE is less than 10%.
MICROBIOLOGY
 Streptococcal spp- Beta-hemolytic Strept
 Beta-hemolytic streptococci have remained uniquely
susceptible to penicillin, with extremely rare
exception.
 Nevertheless, it is prudent to obtain susceptibility

testing on all isolates.
 Surgery is often required for management of severe

valvular and perivalvular involvement.
MICROBIOLOGY
 Streptococcal spp- S. gallolyticus (Group D)
 Streptococcus gallolyticus (formerly known as S.
bovis)
 The organism usually is found in the gastrointestinal
tract
 When it is recovered from blood culture, whether related
to IE or not, an examination for an underlying
gastrointestinal lesion, including colon cancer, should be
performed.
 Although it currently is the cause of less than 10%
of cases of IE, the expectation is that it will become
more prominent in aging populations and in
populations with increasing restrictions on cancer
prevention screening.
MICROBIOLOGY
 Streptococcal spp- S.pneumoniae
IE due to Streptococcus pneumoniae
 Historically,
has received considerable attention.
 Although it continues to be a common cause of

community-acquired bloodstream infection that
often is related to pneumonia, it is a rare cause of IE
today.
 When it does cause IE, the clinical presentation

usually is that of an acute syndrome associated with
valve destruction.
MICROBIOLOGY
 Streptococcal spp- S.pneumoniae
 It can be associated with meningitis as well as other
intracranial complications.
 Invasive isolates of pneumococci tend to be

penicillin-susceptible, but susceptibility testing is
required to confirm this impression.
 As with IE due to beta-hemolytic streptococci,

surgery often is required to address valve-related
complications.
MICROBIOLOGY
 Staphylococcal spp- S.aureus
 The staphylococci are the second group of gram-
positive cocci that are well recognized as causes of
IE.
 S. aureus is a common cause of both native and
prosthetic valve endocarditis
 The presentation in cases caused by S. aureus is
acute in onset and associated with considerable
systemic toxicity.
 In cases of left-heart infection, morbidity and
mortality rates are high, despite appropriate therapy
including surgical intervention.
MICROBIOLOGY
 Staphylococcal spp- S.aureus
 Right-heart infection, predominantly of the tricuspid
valve in injection drug users, has a much higher cure
rate than that for left heart infection, and mortality
rates are low, unless bilateral infection is present.
 Unfortunately, the rate of IE due to S. aureus is

increasing, owing in part to an increased exposure to
health care.
 In addition, resistance to oxacillin and other

antibiotics also has increased, which has made
treatment more difficult.
MICROBIOLOGY
 Staphylococcal spp- CONS
 Frequent pathogens of prosthetic valve infection
 They also can cause native valve infection in a

minority of IE cases
 Although these infections usually are subacute in

presentation, the morbidity and mortality associated
with IE due to coagulase-negative staphylococci are
considerable
MICROBIOLOGY
 Of the more than 30 species of coagulase-negative
staphylococci, two deserve special attention:
 Staphylococcus epidermidis is the most commonly

identified species to cause bacteremia and IE.
 Staphylococcus lugdunensis is another species that causes

both native and prosthetic valve endocarditis and tends to
be more virulent than the other species of CONS
MICROBIOLOGY
 Because this group of organisms is the most common
cause of contaminated blood cultures, a delay in
diagnosis can occur, due to misinterpretation of
blood culture results
 Multiple sets of blood culture specimens should
therefore be collected to better distinguish
contamination from bloodstream infection
 Except for S. lugdunensis, many strains of which
remain penicillin-susceptible, coagulase-negative
staphylococci are more drug-resistant than S.
aureus; accordingly, fewer treatment options are
available
MICROBIOLOGY
 Enterococcal Species
 Age is strongly associated with the development of
IE due to enterococcal species
 The prevalence of these organisms in IE cases double
among elderly persons as compared with young adults
A majority of infections are due to Enterococcus

faecalis and are associated with genitourinary tract
abnormalities.
MICROBIOLOGY
 In the past, enterococcal IE was community-
acquired, and enterococci were well recognized as
part of the normal gut flora in humans.
 More recently, enterococcal species associated with

health care exposure and central venous catheter
use have contributed to infection predisposition.
 With this group of organisms, a subacute IE

presentation is typical, and antibiotic therapy
requires penicillin or ampicillin combined with an
aminoglycoside, usually gentamicin.
MICROBIOLOGY
 Multi-drug-resistant enterococcal species, in
particular, Enterococcus faecium, can cause IE that
is difficult to cure
 This includes infection due to vancomycin-resistant

strains collectively termed vancomycin-resistant
enterococci (VRE).
MICROBIOLOGY
 HACEK Organisms
 The HACEK organisms are fastidious gram negative bacilli
 Comprise of
 Haemophilus species (other than Haemophilus influenzae),
 Actinomycetem comitans (formerly Actinobacillus
actinomycetemcomitans), & Aggregatibacter aphrophilus (formerly

Haemophilus aphrophilus),
 Cardiobacterium hominis ,
 Eikenella corrodens ,
 Kingella kingae, and Kingella denitrificans
 Accounts for approximately 5%-10% of community-acquired

native-valve endocarditis cases in patients who do not use
intravenous drugs
MICROBIOLOGY
 HACEK Organisms
 They colonize in the oropharynx and upper
respiratory tract, causing subacute IE presentation
that is community-acquired.
 Most of the organisms in blood cultures may require
several days of incubation.
 Owing to the indolent clinical course, diagnosis often
is delayed, with the formation of large vegetations
observed at echocardiography.
 As a result, embolism to the brain or other systemic

sites occurs frequently.
MICROBIOLOGY
 Aerobic Gram-Negative Bacilli
 In view of their universal causation of bloodstream
infection, it is noteworthy that IE due to aerobic
gram-negative bacilli is rare.
 Old reports: 1.3%; Recent reports: 2.1%
 This observation attests to the unique virulence
factors that characterize gram-positive cocci in IE
pathogenesis that are not found in gram-negative
bacilli
 This group includes Escherichia coli, Klebsiella

species, Enterobacter species, Pseudomonas species,
and others
MICROBIOLOGY
 Aerobic Gram-Negative Bacilli
 In cases of IE caused by these organisms,
presentations generally have been acute and
sometimes associated with systemic toxicity,
including sepsis and its complications
 IE can be either community- or health care–

associated
 Outcomes of IE due to aerobic gram-negative bacilli

are characterized by increased morbidity and
mortality rates
MICROBIOLOGY
 Fungi
 Fungi are extremely rare causes of IE.
 Identification of these organisms often is difficult,

because some of them do not grow in routine blood
culture media.
 Even when selected culture media are used, fungal

isolation may not be achieved.
 Thus fungi can cause either blood culture–positive or

culture-negative IE.
MICROBIOLOGY
 Fungi
 The bulk of these infections are due to Candida
species, although a broad array of fungi may cause
IE.
 These infections usually are health care–associated
and involve prosthetic valves, often arising as a
result of a central venous catheter infection
 An indwelling right-heart catheter, such as a
flotation catheter, can denude a valve and/or
nonvalvular endothelial surface, thereby predisposing
the patient to fungal (or bacterial) right-sided IE.
 In addition, injection drug use is a well recognized
risk factor for fungal IE
MICROBIOLOGY
 Fungi
 Clinical
presentations range in severity from acute to
subacute.
 Complications are frequent, and surgical intervention

is recommended as a routine intervention,
particularly with infections due to molds such as
Aspergillus species.
 Because relapsing IE is a concern and can be delayed

in onset, many clinicians advocate the use of lifelong
oral antifungal-suppressive therapy, usually with an
azole, after initial parenteral therapy is completed
MICROBIOLOGY
 Culture-Negative Endocarditis
 5-15% of all infective endocarditis
 In one-third to one-half of these cases, cultures are

negative because of prior antibiotic exposure.
 The remainder of these patients are infected by

fastidious organisms, such as nutritionally variant
organisms
 Now designated Granulicatella and Abiotrophia species,
HACEK organisms, Coxiella burnetii, and Bartonella
species.
MICROBIOLOGY
 Culture-Negative Endocarditis
 In the former scenario, nothing can be done
 In the latter, blood cultures can be held for an extended

period, at least 14 days, to determine if an isolate is recovered.
 Other techniques, such as special culture methods or serologic

studies, also are used to isolate or identify infection.
 Some fastidious organisms occur in characteristic
geographic settings
 E.g.,C. burnetii and Bartonella species in Europe, Brucella
species in the Middle East
 Tropheryma whipplei causes an indolent, culture-negative,
afebrile form of endocarditis.
 Health care–associated NVE, commonly caused
by Staphylococcus aureus, coagulase-negative
staphylococci (CoNS), and enterococci
 Has a nosocomial onset (55%) or a community onset
(45%) in patients who have had extensive contact
with the health care system over the preceding 90
days.
 Endocarditis complicates 6–25% of episodes of
catheter-associated S. aureus bacteremia; the
higher rates are detected by careful TEE.
 Prosthetic valve endocarditis (PVE) arising within

2 months of valve surgery is generally
nosocomial, the result of intraoperative
contamination of the prosthesis or a bacteremic
postoperative complication
 This nosocomial origin is reflected in the primary
microbial causes:
 S. aureus, CoNS, facultative gram-negative bacilli,
diphtheroids, and fungi.
 The portals of entry and organisms causing cases

beginning >12 months after surgery are similar to
those in community-acquired NVE.
 PVE due to CoNS that presents 2–12 months
after surgery often represents delayed-onset
nosocomial infection.
 Regardless of the time of onset after surgery,

at least 68–85% of CoNS strains that cause PVE
are resistant to methicillin.
 Transvenous pacemaker– or implanted
defibrillator–associated endocarditis is usually
nosocomial.
 The majority of episodes occur within weeks of
implantation or generator change and are caused by
S. aureus or CoNS, both of which are commonly
resistant to methicillin.
Endocarditis related to a permanent pacemaker or an
implantable cardioverter-defibrillator involves the device or
the endothelium at points of device contact. Occasionally,
there is concurrent aortic or mitral valve infection. One-
third of cases of CIED endocarditis present within 3 months
after device implantation or manipulation, one-third present
at 4–12 months, and one-third present at >1 year. S. aureus
and CoNS, both of which are commonly resistant to
methicillin, cause the majority of cases
41
 Endocarditis occurring among injection drug
users, especially that involving the tricuspid
valve, is commonly caused by S. aureus, many
strains of which are resistant to methicillin.
 Why are IDUs predisposed more for right sided IE?
 Left-sided valve infections in addicts have a

more varied etiology.
 In addition to the usual causes of endocarditis,
these cases are caused by Pseudomonas aeruginosa
and Candida species and sporadically by unusual
organisms such as Bacillus, Lactobacillus, and
Corynebacterium species.
PATHOGENESIS
 Two overarching aspects of endocarditis
pathogenesis have been identified
1. Underlying valvular or nonvalvular cardiac
structural abnormality
2. Infection may involve normal valves

PATHOGENESIS
 Underlying valvular or nonvalvular cardiac
 Accounts for the majority of IE
 The endothelium, unless damaged, is resistant to

infection by most bacteria and to thrombus
formation.
 Endothelial injury allows either direct infection by

virulent organisms or the development of an
uninfected platelet-fibrin thrombus—a condition
called nonbacterial thrombotic endocarditis (NBTE).
PATHOGENESIS
 The thrombus subsequently serves as a site of
bacterial attachment during transient bacteremia.
 The cardiac conditions most commonly resulting in

NBTE are mitral regurgitation, aortic stenosis, aortic
regurgitation, ventricular septal defects, and
complex congenital heart disease.
PATHOGENESIS
 NBTE also arises as a result of a hypercoagulable
state; this phenomenon gives rise to
 Marantic endocarditis (uninfected vegetations seen in
patients with malignancy and chronic diseases) and
 Bland vegetations complicating systemic lupus

erythematosus and the antiphospholipid antibody
syndrome.
PATHOGENESIS
 Organisms that cause endocarditis generally enter
the bloodstream from mucosal surfaces, the skin, or
sites of focal infection.
 Except for more virulent bacteria (e.g., S. aureus)

that can adhere directly to intact endothelium or
exposed subendothelial tissue, microorganisms in the
blood adhere at sites of NBTE.
PATHOGENESIS
 This picture of pathogenesis is mirrored, in many
ways, by the animal model of endocarditis that has
been used for decades to examine the pathogenesis,
treatment, and prevention of IE
 The microbiologic and histopathologic findings in

infected animals are reflective of those seen in
humans
PATHOGENESIS
 IE of a normal valve
 Some reservations regarding this pathway of
infection seem appropriate, because it is impossible
to know if a valve is completely normal, including its
endothelial surface, before onset of valve infection.
 In addition, animals do not develop experimental

endocarditis after an intravascular challenge with a
relatively large inoculum of virulent organisms, in
particular S. aureus, in the absence of a previous
disruption of the cardiac endothelial surface.
 Nevertheless, in vitro endothelial cell cultures studies have
demonstrated uptake of organisms by endothelial cells.
PATHOGENESIS
 The organisms proliferate and induce platelet
deposition and a procoagulant state at the site
by eliciting tissue factor from the endothelium
or, in the case of S. aureus, from monocytes as
well.
 Fibrin deposition combines with platelet

aggregation and microorganism proliferation to
generate an infected vegetation.
PATHOGENESIS
 Why are G+ve much more dominant in IE?
 Advances in molecular biologic techniques have
resulted in the ability to define virulence factors
that are unique to these organisms
 Some of these factors serve as “adhesins” and are

largely responsible for initial bacterial attachment to
an NBTE nidus or to endothelial cells. (see below)
 They also are responsible for the attachment to medical
devices, including prosthetic valves and cardiovascular
implantable electronic device (CIED) leads.
PATHOGENESIS
 Why are G+ve much more dominant in IE?
 In this regard, biofilm formation occurs with some
of these organisms and is important in both native
tissue and prosthetic valve infections in the context
of factors that are responsible for the propagation
of IE after initial bacterial attachment.
PATHOGENESIS
 Adhesion molecules
 Organisms that commonly cause endocarditis have
surface adhesin molecules
 These are collectively called microbial surface

components recognizing adhesin matrix molecules
(MSCRAMMs), that mediate adherence to NBTE
sites or injured endothelium.
PATHOGENESIS
 Adhesion molecules
 Fibronectin-binding proteins present on many gram-
positive bacteria, clumping factor (a fibrinogen- and
fibrin-binding surface protein) on S. aureus, and
glucans or FimA (a member of the family of oral
mucosal adhesins) on streptococci facilitate
adherence.
 Fibronectin-binding proteins are required for S.

aureus invasion of intact endothelium; thus these
surface proteins may facilitate infection of
previously normal valves.
PATHOGENESIS
 In the absence of host defenses, organisms
enmeshed in the growing platelet-fibrin
vegetation proliferate to form dense
microcolonies.
 Organisms deep in vegetations are metabolically

inactive (nongrowing) and relatively resistant to
killing by antimicrobial agents.
 Proliferating surface organisms are shed into

the bloodstream continuously
PATHOGENESIS
 The pathophysiologic consequences and clinical
manifestations of endocarditis arise from
 Damage to intracardiac structures;
 Embolization of vegetation fragments, leading to
infection or infarction of remote tissues;
 Hematogenous infection of sites during bacteremia;
and
 Tissue injury due to the deposition of circulating
immune complexes or immune responses to deposited
bacterial antigens.
PATHOGENESIS
 Why regurgitant lesions are affected more?
 Preexisting valvular regurgitant lesions are far more
prone to infection than stenotic lesions.
 It has been suggested that the incidence of IE is
directly related to the impact of pressure on the
closed valve, with shear stress disruption of the
valvular endothelium in the vicinity of the egressing
regurgitant jet.
 In the presence of the Venturi effect, circulating
organisms are deposited within the high-velocity,
loweredpressure eddy zones of the regurgitant
orifice of the receiving chamber, leading to the
typical localization of vegetations on the upstream
aspect of the infected valve
PATHOGENESIS
 Physics of low pressure side and endocarditis
 The velocity of the stream is a function of the
pressure gradient from source to sink.
 Ifthe orifice were wide, the large flow across it

would quickly dissipate the gradient;
 However, when the orifice is narrow, the volume of

the shunt will be small and a large pressure gradient
and a high velocity will persist.
PATHOGENESIS
 As fluid enters an orifice, momentum causes the
streamlines to continue to converge, with the result
that the velocity is greatest a short distance
beyond the anatomic constriction, at the vena
contracta.
 This appears to be the consistent locus of the
endocarditic process.
 It is at this point that hydrodynamic factors operate
through two discrete mechanisms to reduce the
contact of stream-borne materials with the vessel
walls
 By the pattern of stream line flow and
 By reduction in the rate of vascular perfusion.
PATHOGENESIS
PATHOGENESIS
 The quanltity of nultritive and defensive materials
passing from the blood stream to the vascular lining
depends in large part on
 The contact of stream-borne materials with the endothelium
and
 The rate of fliltration of plasma components into the intima
 When layers of the stream more smoothly with

respect to eachother, as occurs in most normal blood
vessels, only the boundary lamina comes in contact
with the wall
 This relatively slow moving layer bring only a very limited
quantity of streamborne materials to the wall
PATHOGENESIS
 Streamlines passing through a nozzle continue to
converge for a short distance beyond the orifice
because of momentum
 As a result, a small sector of the vessel at the vena

contracta have only negligible contact with the
materials of the stream
CLINICAL MANIFESTATIONS
 The clinical syndrome of infective endocarditis is
highly variable and spans a continuum between
acute and subacute presentations.
 NVE (whether acquired in the community or in

association with health care), PVE, and
endocarditis due to injection drug use share
clinical and laboratory manifestations.
 The causative microorganism is primarily responsible
for the temporal course of endocarditis.
 Beta hemolytic streptococci, S. aureus, and pneumococci
typically result in an acute course, although S. aureus
occasionally causes subacute disease.
 Endocarditis caused by Staphylococcus lugdunensis (a
coagulase-negative species) or by enterococci may
present acutely.
 Subacute endocarditis is typically caused by viridans
streptococci, enterococci, CoNS, and the HACEK group.
 Endocarditis caused by Bartonella species, Tropheryma
whipplei, or C. burnetii is exceptionally indolent.
 The clinical features of endocarditis are
nonspecific.
 However, these symptoms in a febrile patient with
valvular abnormalities or a behavior pattern that
predisposes to endocarditis (e.g., injection drug use)
suggest the diagnosis
 Diagnosis is also suggested by bacteremia with

organisms that frequently cause endocarditis,
otherwise-unexplained arterial emboli, and
progressive cardiac valvular incompetence.
 Fever
 In patients with subacute presentations, fever is
typically low-grade and rarely exceeds 39.4°C
(103°F)
 In contrast, temperatures of 39.4°–40°C (103°–

104°F) are often noted in acute endocarditis.
 Fever may be blunted or absent in patients who are

elderly or severely debilitated or who have marked
cardiac or renal failure
 Fever
 Fever may be absent in up to 20% of cases,
particularly in
 Elderly persons,
 The immunocompromised,
 Patients treated with previous empirical antibiotic therapy,
or
 Patients with infections of implantable cardiac device.
 Fever
 Fever defervescence usually occurs within 5 to 7
days of appropriate antibiotic therapy.
 Persistence of fever may indicate

 Progressive infection with perivalvular extension such as
abscess,
 Septic embolization,
 An extracardiac site of infection (native or prosthetic),
 Infected indwelling catheters or devices,
 Inadequate antibiotic treatment of a resistant organism,
or
 Even an adverse reaction to the antibiotic therapy itself
 Valvular damage and ruptured chordae may
result in new regurgitant murmurs.
 In acute endocarditis involving a normal valve,
murmurs may be absent initially but ultimately are
detected in 85% of cases.
 CHF develops in 30–40% of patients; it is usually

a consequence of valvular dysfunction but
occasionally is due to endocarditis-associated
myocarditis or an intracardiac fistula.
 Heart failure due to aortic valve dysfunction
progresses more rapidly than does that due to
mitral valve dysfunction. Why?
 Extension of infection beyond valve leaflets into

adjacent annular or myocardial tissue results in
perivalvular abscesses, which in turn may cause
intracardiac fistulae with new murmurs.
 Abscesses may burrow from the aortic valve
annulus through the epicardium, causing
pericarditis, or into the upper ventricular
septum, interrupting the conduction system,
leading to varying degrees of heart block.
 Perivalvular abscesses arising from the mitral valve
rarely interrupt conduction pathways near the
atrioventricular node or in the proximal bundle of
His
 Emboli to a coronary artery occur in 2% of patients
and may result in myocardial infarction.
 The classic nonsuppurative peripheral
manifestations of subacute endocarditis are
related to the duration of infection and, with
early diagnosis and treatment, have become
infrequent.
 In contrast, septic embolization mimicking some

of these lesions (subungual hemorrhage, Osler's
nodes) is common in patients with acute S.
aureus endocarditis.
 Musculoskeletal pain usually remits promptly with
treatment but must be distinguished from focal
metastatic infections (e.g., spondylodiscitis),
which may complicate 10–15% of cases.
 Hematogenously seeded focal infection is most

often clinically evident in the skin, spleen,
kidneys, skeletal system, and meninges
 Spleen-found to be the second commonest site of
metastasis in a recent study
 Splenomegaly- seen in ~10% of patients
 LUQ tenderness can be the presentation
 Arterial emboli are clinically apparent in up to
50% of patients.
 Increased risk of embolization is associated

independently with
 Endocarditis caused by S. aureus,
 Vegetations >10 mm in diameter, and
 Infection involving the mitral valve- Why?
 Emboli occurring late during or after effective
therapy do not in themselves constitute evidence
of failed antimicrobial treatment
 Cerebrovascular emboli presenting as strokes or

occasionally as encephalopathy complicate 15–
35% of cases of endocarditis
 One-half of these events precede the diagnosis

of endocarditis
 The frequency of stroke is 8 per 1000 patient-
days during the week prior to diagnosis
 The figure falls to 4.8 and 1.7 per 1000 patient-days
during the first and second weeks of effective
antimicrobial therapy, respectively.
 This decline exceeds that which can be attributed to
change in vegetation size.
 Only 3% of strokes occur after 1 week of

effective therapy
 Other neurologic complications include
 Aseptic or purulent meningitis,
 Intracranial hemorrhage due to hemorrhagic infarcts
or ruptured mycotic aneurysms, and
 Seizures.
N.B. Mycotic aneurysms are focal dilations of arteries
occurring at points in the artery wall that have been
weakened by infection in the vasa vasorum or where
septic emboli have lodged.
 Microabscesses in brain and meninges occur
commonly in S. aureus endocarditis; surgically
drainable intracerebral abscesses are
infrequent.
 Immune complex deposition on the glomerular
basement membrane causes diffuse
hypocomplementemic glomerulonephritis and
renal dysfunction, which typically improve with
effective antimicrobial therapy.
 Embolic renal infarcts cause flank pain and

hematuria but rarely cause renal dysfunction
 Janeway lesions
 Macular, nonpainful, erythematous lesions on the
palms and soles
 Pathologically,
the lesion is described to be a
microabscess of the dermis with marked necrosis
and inflammatory infiltrate not involving the
epidermis.
 They are caused by septic emboli which deposit

bacteria, forming microabscesses
 Osler's nodes
 Red-purple, slightly raised, tender lumps, often with
a pale centre.
 Pain often precedes the development of the visible
lesion by up to 24 hours.
 They are typically found on the fingers and/or toes.
 They can occur at any time during the course of
endocarditis (usually subacute) and last from hours
to several days.Can be seen in 10-25% of patients
with IE
 Osler’s node ctd
 Though to be due to immune complex deposition
 It can also be seen in

 Systemic lupus erythematosus
 Marantic endocarditis
 Disseminated gonococcal infection
 Distal to infected arterial catheter
 Osler’s node & Janeway lesion
 The pathogenesis of Osler's nodes and Janeway
lesions remains a mystery despite vigorous debate
over the last 113 years.
 Although the appearance is usually consistent, it is

not always possible to distinguish Osler's nodes from
Janeway lesions based purely on clinical presentation.
Furthermore, the histology of both clinical signs can
look similar.
 Roth's spots
 named after Moritz Roth
 Exudative, edematous hemorrhagic lesions of the retina.
 Are retinal hemorrhages with white or pale centers.
 Present-day analysis shows that they can be composed of
coagulated fibrin including platelets, focal ischemia,
inflammatory infiltrate, infectious organisms, or
neoplastic cells.
 They are usually caused by immune complex mediated
vasculitis often resulting from bacterial endocarditis.
 Roth's spots may be observed in leukemia, diabetes,
subacute bacterial endocarditis, pernicious anemia,
ischemic events, hypertensive retinopathy and rarely in
HIV retinopathy.
 Splinter hemorrhages
 Tiny blood clots that tend to run vertically under the
nails.
 Splinter hemorrhages are not specific to any
particular condition
 Can be associated with subacute
infective endocarditis, scleroderma, trichinosis,
systemic lupus erythematosus (SLE),
rheumatoid arthritis, psoriatic nails,[1]
antiphospholipid syndrome, haematological
malignancy, and trauma
 Due to advances leading to earlier diagnosis and
therapy, these classic peripheral manifestations
of IE are now uncommonly observed
 Petechiae are the most common, occurring on the

conjunctivae, oral mucosa, or extremities
 Aside from petechiae and conjunctival

hemorrhage, these peripheral findings were
detected in less than 10% of patients in the
recent ICE-PCS cohort
 Almost 50% of endocarditis cases associated
with injection drug use are limited to the
tricuspid valve and present with fever but with
faint or no murmur.
 In 75% of cases, septic emboli cause cough,

pleuritic chest pain, nodular pulmonary
infiltrates, or occasionally pyopneumothorax.
 Infection of the aortic or mitral valves on the
left side of the heart presents with the typical
clinical features of endocarditis.
 Health care–associated endocarditis has typical

manifestations if it is not associated with a
retained intracardiac device or masked by the
symptoms of concurrent comorbid illness.
 Transvenous pacemaker– or implanted
defibrillator–associated endocarditis may be
associated with obvious or cryptic generator
pocket infection and results in fever, minimal
murmur, and pulmonary symptoms due to septic
emboli.
 Late-onset PVE presents with typical clinical
features.
 In cases arising within 60 days of valve surgery
(early onset), typical symptoms may be obscured by
comorbidity associated with recent surgery.
 In both early-onset and more delayed
presentations, paravalvular infection is common
and often results in partial valve dehiscence,
regurgitant murmurs, CHF, or disruption of the
conduction system
GENERAL LAB
 CBC
 Normochromic normocytic anemia of variable
severity in SBE
 Often with low serum iron and total iron binding capacity.
 Even with the systemic infection of IE, a
leukocytosis with a left differential shift may be
detected in only 50% to 60% of patients and is more
common with acute than with subacute IE.
 Leukopenia also may uncommonly occur with subacute
IE and usually is associated with splenomegaly.
GENERAL LAB
 CBC
 Thrombocytopenia may occur in approximately 10%
of patients and has been found to be a predictor of
early adverse outcome in IE.
 Sy and colleagues reported a hazard ratio of

approximately 1.13 for each 20 × 109/L decrement in
the platelet count as a multivariate predictor of
mortality from days 1 to 15 after presentation with
IE.
GENERAL LAB
 ESR: Elevated in 61% of patients in the ICE-PCS
cohort study
 Elevated ESR was independently associated with a
decreased risk of in-hospital death, presumably
owing to association with subacute IE with a more
indolent course
 CRP: Elevated 60% of patients
 Rheumatoid factor concentration was abnormal

in 5%
GENERAL LAB
 A new elevation in serum creatinine occurs in
10% to 30% of patients
 May be related to multifactorial reasons including
 Renal hypoperfusion due to severe sepsis or heart failure,
 Embolic renal infarction,
 Immune complex–mediated glomerulonephritis, and
 Toxicity from either antibiotic therapy or contrast agents
used for imaging

GENERAL LAB
 Renal dysfunction developing within the first 8
days of presentation is independently predictive
of early IE mortality
 HR: 1.13 per incremental increase in serum creatinine
of 0.23 mg/Dl
 And persistent serum creatinine elevation to greater

than 2 mg/dL is predictive of 2-year mortality.
GENERAL LAB
 Urinalysis commonly demonstrates hematuria,
and proteinuria.
 In cases of immune complex glomerulonephritis,

red blood cell casts are evident, associated with
depressed serum complement levels.
ECG
 Conduction blocks
 Owing to the close proximity of the atrioventricular
node and proximal intraventricular conduction system
to the aortic valve and root, perivalvular extension of
infection from this location can cause AVB or BBB
 With perivalvular extension of infection, the

incidence of AVB ranges from 10% to 20%, whereas
new bundle branch block occurs in approximately 3%
 The occurrence of a new conduction abnormality also

is a multivariate risk predictor for death associated
with IE
ECG
 Ischemia
 More uncommonly, perivalvular extension
complicating aortic valve IE may compromise
proximal coronary artery patency, or emboli from
aortic valve vegetations may cause damage resulting
in ischemic ECG changes or even ST-segment
elevation acute coronary syndromes
 Others
 Other atrial and ventricular arrhythmias may
potentially complicate structural or hemodynamic
complications of IE but have not been systematically
examined in the recent literature.
DIAGNOSIS
 The diagnosis of infective endocarditis is
established with certainty only when vegetations
are examined histologically and microbiologically.
 More recently, ICE-PCS* has detailed the

clinical presentation in 2781 patients with
definite IE.
 Native valve IE was predominant (72%), followed by
 Prosthetic valve endocarditis (21%) and
 Pacemaker or ICD IE (7%).
DIAGNOSIS
 Consistent with numerous earlier series, this
international cohort study found that IE
manifests with definite vegetations most
commonly in the
 Mitral valve position (41%), followed by
 Aortic valve position (38%),
 The tricuspid (12%) and
 Pulmonary (1%)
DIAGNOSIS
 1994: A highly sensitive and specific diagnostic
schema—known as the Duke criteria—has been
developed on the basis of clinical, laboratory,
and echocardiographic findings
 Sensitivity:~80%,
 Both specificity and negative predictive value
exceeding 90%.
 2000: Modified Duke’s criteria

 Liand colleagues
 Validated subsequently with diagnostic accuracy
DIAGNOSIS
 Clinical diagnosis of definite endocarditis is
made with documentation of
 Two major criteria,
 One major criterion and three minor criteria, or
 Five minor criteria
 The diagnosis of endocarditis is rejected if

 An alternative diagnosis is established,
 Symptoms resolve and do not recur with ≤4 days of
antibiotic therapy, or
 Surgery or autopsy after ≤4 days of antimicrobial
therapy yields no histologic evidence of endocarditis
DIAGNOSIS
 Possible infective endocarditis: Either one
major criterion and one minor criterion or three
minor criteria are fulfilled.
 The requirement for multiple positive blood

cultures over time is consistent with the
continuous low-density bacteremia characteristic
of endocarditis.
PRECIPITATING FACTOR
 Valvular disease with stenosis or regurgitation,
 presence of a prosthetic valve, congenital heart
disease including corrected or
 partially corrected conditions (except isolated
atrial septal defect, repaired ventricular septal
defect, or closed patent ductus arteriosus),
prior endocarditis, or
hypertrophiccardiomyopathy.
111
DIAGNOSIS- DUKE’S CRITERIA
Major Criteria
1. Positive blood culture
a- Typical microorganism for infective endocarditis from two separate blood cultures
Viridans streptococci, Streptococcus gallolyticus, HACEK group, Staphylococcus
aureus, or Community-acquired enterococci in the absence of a primary focus, or
b- Microorganisms consistent with IE from persistently positive blood cultures, defined as
follows:
Blood cultures drawn >12 h apart; or
All of 3 or a majority of 4 separate blood cultures, with first and last drawn at least 1 h
apart
Single positive blood culture for Coxiella burnetii or antiphase I IgG antibody titer of
>1:800
Major Criteria
2. Evidence of endocardial involvement
a-Positive echocardiogramb
- Oscillating intracardiac mass on valve or supporting structures
or in the path of regurgitant jets or in implanted material, in the
absence of an alternative anatomic explanation, or
- Abscess, or
- New partial dehiscence of prosthetic valve, or
- New valvular regurgitation (increase or change in preexisting
murmur not sufficient)
Minor Criteria
1. Predisposition: predisposing heart condition or injection drug use
2. Fever >38.0°C (100.4°F)
3. Vascular phenomena: major arterial emboli, septic pulmonary
infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival
hemorrhages, Janeway lesions
4. Immunologic phenomena: glomerulonephritis, Osler's nodes,
Roth's spots, rheumatoid factor
5. Microbiologic evidence: positive blood culture but not meeting
major criterion as noted previouslyc or serologic evidence of active
infection with organism consistent with infective endocarditis
BLOOD CULTURE
 Among patients with untreated endocarditis who
ultimately have a positive blood culture, 95% of
all blood cultures are positive
 The diagnostic criteria attach significance to

the species of organism isolated from blood
cultures.
BLOOD CULTURE
 Isolation of the causative microorganism from
blood cultures is critical for diagnosis,
determination of antimicrobial susceptibility, and
planning of treatment.
 In the absence of prior antibiotic therapy, three

2-bottle blood culture sets, separated from one
another by at least 1 h, should be obtained from
different venipuncture sites over 24 h
BLOOD CULTURE
 If the cultures remain negative after 48–72 h,
two or three additional blood culture sets should
be obtained, and the laboratory should be
consulted for advice regarding optimal culture
techniques.
 Pending culture results, empirical antimicrobial

therapy should be withheld initially from
hemodynamically stable patients with suspected
subacute endocarditis,
 Especiallythose who have received antibiotics within
the preceding 2 weeks
BLOOD CULTURE
 If necessary, additional blood culture sets can
be obtained without the confounding effect of
empirical treatment
 Patients with acute endocarditis or with

deteriorating hemodynamics who may require
urgent surgery should be treated empirically
immediately after three sets of blood cultures
are obtained over several hours.
BLOOD CULTURE
 In patients with prosthetic valves, early
prosthetic valve endocarditis has been defined
as occurring as early as 60 days or less and up to
1 year after surgery.
 In the large ICE-PCS cohort study, 62% of

patients with culture-negative IE had received
antibiotic therapy within 7 days of obtaining the
initial blood culture
NON BLOOD CULTURE TESTS
 Serologic tests can be used to implicate causally
some organisms that are difficult to recover by
blood culture:
 Brucella, Bartonella, Legionella, Chlamydophila
psittaci, and C. burnetii.
 Pathogens can also be identified in vegetations

by culture, microscopic examination with special
stains (i.e., the periodic acid–Schiff stain for T.
whipplei), or direct fluorescence antibody
techniques and by the use of PCR
ECHOCARDIOGRAPHY
 Echocardiography allows anatomic confirmation
of infective endocarditis, sizing of vegetations,
detection of intracardiac complications, and
assessment of cardiac function.
 TTE is noninvasive and exceptionally specific;

however, it cannot image vegetations <2 mm in
diameter, and in 20% of patients it is technically
inadequate because of emphysema or body
habitus
ECHOCARDIOGRAPHY FOR NVE
 TTE detects vegetations in only 65% of patients
with definite clinical endocarditis.
 Sensitivity of TTE for NVE

 Early-generation imaging systems: 40 - 60%
 Recent advances: 82% and as high as 89% if high-
quality transthoracic images are available
 Specificity of TTE for NVE: 70 - 90%

 TEE circumvents multiple potential impediments
to TTE imaging, such as body habitus, pulmonary
disease, and other sources of acoustic
interference between the chest wall and heart.
 Owing to much closer proximity of the

transducer to the heart, TEE is performed with
higher-frequency imaging, greatly enhancing
spatial resolution
 With numerous imaging projections available,
multiplane two-dimensional and threedimensional
TEE can characterize vegetations with a
resolution size of approaching 2 to 3 mm
 Sensitivity: 90% to 100%
 Specificity: >90%
ECHOCARDIOGRAPHY FOR PVE
 A lower incidence of valvular vegetations and
higher incidence of periannular infection and
associated complications
 Sensitivity of TTE for PVE is 36-69%
 TEE
 Sensitivity: 80% to 95% and
 Specificity: >90%
 So, TEE clearly is the imaging procedure of

choice for the evaluation of suspected
prosthetic valve endocarditis
ECHOCARDIOGRAPHY FOR PVE
 Differential diagnosis for mobile echodensities
on echocardiography
 Degenerative changes in a native valve, such as
Lambl’s excrescences,
 Endocardial fenestrations,
 Ruptured or retracted chordae, and
 Even acoustic artifacts reflected by calcified tissue
ECHOCARDIOGRAPHY
 Valvular thickening, myxomatous changes, and
sclerotic lesions:
 Move in concert with leaflet or cusp motion, without
independent mobility of a vegetation
 May be difficult to discern from sessile vegetations
 Filamentous valvular strands may be seen on both

native and prosthetic valves.
 Thrombus associated with prosthetic valves may
or may not be infected.
 Valvular neoplasms, such as papillary
fibroelastoma or rarely, myxomas, also are
included in the differential possibilities.
ECHOCARDIOGRAPHY
 Vegetations
 located on the upstream, lower-pressure side of the
regurgitant valve,
 have soft, tissue echocardiographic density
(particularly early in the course of infection) and
 often are multiple and lobulated, with motion
independent of the valve structure.
 Hyperrefractile, discretely nodular, or

filamentous echo densities located on the
downstream side of the valve are far less likely
to represent vegetations associated with IE
ECHOCARDIOGRAPHY
 Read Braunwald p. 1799-1803 for further on
imaging
ECHOCARDIOGRAPHY
 When endocarditis is likely, a negative TEE
result does not exclude the diagnosis but rather
warrants repetition of the study in 7–10 days.
 TEE is the optimal method for the diagnosis of

PVE or the detection of myocardial abscess,
valve perforation, or intracardiac fistulae.
 Echocardiography should not be used to screen

patients with a low probability of endocarditis
(e.g., patients with unexplained fever).
OTHER STUDIES
 CBC, creatinine determination, liver function
tests, chest radiography, and
electrocardiography
 ESR, CRP and circulating immune complex titer

are commonly increased in endocarditis.
 Cardiac catheterization is useful primarily to

assess coronary artery patency in older
individuals who are to undergo surgery for
endocarditis.
TREATMENT
 It is difficult to eradicate bacteria from the
vegetation because local host defenses are
deficient and because the largely nongrowing,
metabolically inactive bacteria are less easily
killed by antibiotics
 To cure endocarditis, all bacteria in the

vegetation must be killed; therefore, therapy
must be bactericidal and prolonged.
TREATMENT
 Antibiotics are generally given parenterally to
achieve serum concentrations that, through
passive diffusion, lead to effective
concentrations in the depths of the vegetation.
 To select effective therapy requires knowledge

of the susceptibility of the causative
microorganisms.
 The decision to initiate treatment empirically must
balance the need to establish a microbiologic
diagnosis against the potential progression of
disease or the need for urgent surgery
TREATMENT
 Simultaneous infection at other sites (such as
meningitis), allergies, end-organ dysfunction,
interactions with concomitant medications, and
risks of adverse events must be considered in
the selection of therapy.
 Although given for several weeks longer, the

regimens recommended for the treatment of
endocarditis involving prosthetic valves (except
for staphylococcal infections) are similar to
those used to treat NVE
TREATMENT
Organism Drug (Dose, Duration) Comments
Streptococci
Penicillin-susceptbleb Penicillin G (2–3 mU IV q4h —
streptococci, S. for 4 weeks) Can use ceftriaxone in
gallolyticus Ceftriaxone (2 g/d IV as a patients with
single dose for 4 weeks) nonimmediate penicillin
Vancomycinc (15 mg/kg IV allergy
q12h for 4 weeks) Use vancomycin in
Penicillin G (2–3 mU IV patients with severe or
q4h) or ceftriaxone (2 g IV immediate -lactam allergy
qd) for 2 weeks Avoid 2-week regimen
PLUS when risk of
Gentamicind (3 mg/kg qd IV aminoglycoside toxicity is
or IM, as a single dosee or increased and in prosthetic
divided into equal doses q8h valve or complicated
for 2 weeks) endocarditis
TREATMENT
Streptococci
Relatively penicillin- Penicillin G (4 mU IV Penicillin alone at this
resistantf streptococci q4h) or ceftriaxone (2 g IV dose for 6 weeks or with
qd) for 4 weeks plus gentamicin during initial 2
Gentamicind (3 mg/kg qd weeks preferred for
IV or IM, as a single dosee prosthetic valve
or divided into equal doses endocarditis caused by
q8h for 2 weeks) streptococci with penicillin
Vancomycinc as noted MICs of 0.1 g/mL
above for 4 weeks —
TREATMENT
Streptococci
Moderately penicillin- Penicillin G (4–5 mU IV Preferred for prosthetic
resistantg streptococci, q4h) or ceftriaxone (2 g IV valve endocarditis caused
nutritionally variant qd) for 6 weeks plus by streptococci with
organisms, or Gemella Gentamicind (3 mg/kg qd penicillin MICs of >0.1
morbillorum IV or IM as a single dosee g/mL
or divided into equal doses
q8h for 6 weeks)
Vancomycinc as noted
above for 4 weeks —
TREATMENT
Enterococci
Penicillin G (4–5 mU IV q4h) Can use streptomycin (7.5
plus mg/kg q12h) in lieu of
Gentamicind (1 mg/kg IV q8h), gentamicin if there is not
both for 4–6 weeks high-level resistance to
Ampicillin (2 g IV q4h) streptomycin
plus Gentamicind (1 mg/kg IV —
q8h), both for 4–6 weeks
Vancomycinc (15 mg/kg IV
q12h) plus Use vancomycin plus
Gentamicind (1 mg/kg IV q8h), gentamicin for penicillin-
both for 4–6 weeks allergic patients, or
desensitize to penicillin
TREATMENT
Staphylococci
Methicillin-susceptible, Nafcillin or oxacillin (2 g IV q4h
Can use penicillin (4 mU
infecting native valves for 4–6 weeks) q4h) if isolate is penicillin-
(no foreign devices) Cefazolin (2 g IV q8h for 4–6 susceptible (does not produce
weeks) -lactamase)
Vancomycinc (15 mg/kg IV q12h Can use cefazolin regimen for
for 4–6 weeks) patients with nonimmediate
penicillin allergy
Use vancomycin for patients
with immediate (urticarial) or
severe penicillin allergy
Methicillin-resistant, Vancomycinc (15 mg/kg IV q8–12h No role for routine use of
infecting native valves for 4–6 weeks) rifampin
(no foreign devices)
TREATMENT
Staphylococci
Methicillin-susceptible, Nafcillin or oxacillin (2 g IV q4h for
Use gentamicin during initial 2
infecting prosthetic 6–8 weeks) plus weeks; determine susceptibility
valves Gentamicind (1 mg/kg IM or IV q8h to gentamicin before initiating
for 2 weeks) plus Rifampini (300 mg rifampin (see text); if patient is
PO q8h for 6–8 weeks) highly allergic to penicillin, use
regimen for methicillin-resistant
staphylococci; if -lactam allergy
is of the minor, nonimmediate
type, can substitute cefazolin for
oxacillin/nafcillin
Methicillin-resistant, Vancomycinc (15 mg/kg IV q12h for Use gentamicin during initial 2
infecting prosthetic 6–8 weeks) plus weeks; determine gentamicin
valves Gentamicin (1 mg/kg IM or IV q8h susceptibility before initiating
d
for 2 weeks) plus Rifampini (300 mg rifampin (see text)

PO q8h for 6–8 weeks)
TREATMENT

HACEK Organisms
Ceftriaxone (2 g/d IV as a Can use another
single dose for 4 weeks) third-generation
Ampicillin/sulbactam (3 g IV cephalosporin at
q6h for 4 weeks) comparable dosage
—
EMPIRICAL ANTIBIOTIC THERAPY
 Acute endocarditis in an injection drug user:

cover MRSA and gram-negative bacilli
 Vancomycin plus Gentamicin- covers these and other
potential pathogens
 Health care–associated endocarditis must cover
MRSA
 Blood culture–negative subacute NVE*:
 Ampicillin-sulbactam (12 g every 24 h) or
 Ceftriaxone plus Gentamicin;
 Doxycycline (100 mg twice daily) is added for
Bartonella coverage.
 * Exclude Marantic endocarditis; Fastidious
organisms should be sought with serologic
examination; In the absence of prior antibiotic
therapy, it is unlikely that S. aureus, CoNS, or
enterococcal infection will present with negative
blood cultures; thus, in this situation,
recommended empirical therapy targets not
these organisms but rather nutritionally variant
organisms, the HACEK group, and Bartonella
species
EMPIRICAL ANTIBIOTIC THERAPY
 Prosthetic valves in place for >1 year are involved
 Vancomycin, gentamicin, cefepime, and rifampin
 Prosthetic valves in place for ≤1 year
 similar to that for culture-negative PVE
 If negative cultures have been confounded by
prior antibiotic administration, broader empirical
therapy may be indicated, with particular
attention to pathogens likely to be inhibited by
the specific prior therapy
MONITORING OF ANTIBIOTIC THERAPY
 Most patients with IE become afebrile three to
five days after treatment is begun with an
appropriate antibiotic.
 Patientswith S. aureus endocarditis may respond
somewhat more slowly, remaining febrile for five to
seven days after the institution of therapy.
 Repeat blood cultures 48 to 72 hours after
antibiotics are begun.
 Careful serial examinations: for signs of heart
failure, emboli, or other complications.
 Blood cultures should be repeated daily until
sterile, rechecked if there is recrudescent
fever, and performed again 4–6 weeks after
therapy to document cure.
 Blood cultures become sterile within 2 days

after the start of appropriate therapy when
infection is caused by viridans streptococci,
enterococci, or HACEK organisms.
 In S. aureus endocarditis, beta-lactam therapy

results in sterile cultures in 3–5 days, whereas
with MRSA endocarditis positive cultures may
persist for 7–9 days with vancomycin treatment
 When fever persists for 7 days despite
appropriate antibiotic therapy, the following
should be suspected
 Paravalvularabscess,
 Extracardiac abscesses (spleen, kidney), or
 Complications (embolic events).
 Drug reactions or
 Complications of hospitalization.
 Vegetations become smaller with effective

therapy; however, 3 months after cure, 50% are
unchanged and 25% are slightly larger
DISCONTINUING ANTICOAGULATION
 Temporary discontinuation of VKA anticoagulation might be
considered in patients receiving VKA anticoagulation at the
time of IE diagnosis (Class IIb)
 In patients with NVE, routine use of VKA is not recommended
unless a separate indication exists.
 There is no conclusive evidence that prophylactic use of VKA

anticoagulation reduces the incidence of emboli in patients with
NVE who have no other indication for anticoagulation
 The evidence and propensity of expert consensus would
suggest that VKAs be discontinued at the time of initial
presentation with IE secondary to the combined risk of
bleeding from potentially urgent invasive procedures and the
risk of developing hemorrhagic stroke.
 Early surgery is required in roughly 50% of patients with PVE.
 Discontinuation of VKA anticoagulation …
 Alternatively,for patients already receiving
anticoagulation with VKA or aspirin for other
evidence-based indications at the time of diagnosis
with IE, there is little information on the risks and
benefits of continued anticoagulation therapy.
 Continuing anticoagulant therapy in the face of IE

potentially increases the risk of hemorrhagic
transformation of an embolic stroke or accentuation
of bleeding from septic arteritis or mycotic
aneurysms should they occur
 Discontinuation of VKA anticoagulation…
 Although there is no evidence regarding the use of
bridging therapy with intravenous or subcutaneous
anticoagulant therapy while patients are off VKAs,
studies indicate that there is increased risk of
hemorrhagic stroke in patients on intravenous UFH
during the acute phase of acute IE.
It should be noted that the strength of this
evidence is low, and some institutional practices
continue VKA anticoagulation until an invasive
procedure is deemed a definitive necessity or until
a neurological complication develops or is noted on
imaging studies.
 It is reasonable to temporarily discontinue
anticoagulation in patients with IE who develop
central nervous system symptoms compatible with
embolism or stroke regardless of the other
indications for anticoagulation (Class IIa)
 Potential mechanisms of stroke in patients

with IE:-
 Hemorrhagic transformation of an ischemic infarct,
 Septic erosion of an arteritic vessel without
aneurysm formation, and
 Rupture of a mycotic aneurysm
 Approximately 15% to 35% of all patients with
IE develop clinically evident systemic emboli.
 If more sensitive tests such as cerebral magnetic
resonance imaging are used, a much higher
proportion of patients with IE have evidence of
emboli (≥30%).
 The most common cause of stroke in patients

with IE in the modern antimicrobial era is a
septic embolus resulting in ischemia, often
followed by hemorrhagic transformation
 Anticoagulant therapy may increase the risk of
an embolic infarct converting to a hemorrhagic
infarct.
 Hemorrhagic transformations can occur up to 11

days after an initial infarct.
 On the other hand, the longer anticoagulation is

withheld, the higher the chance of recurrent
embolization or valve dysfunction in patients
with PVE.
166
SURGERY
 From 25% to 40% of patients with left-sided
endocarditis undergo cardiac surgery during
active infection, with slightly higher surgery
rates with PVE than with NVE
 Clinical events resulting from intracardiac

complications, which are most reliably detected
by TEE, justify most surgery
SURGERY
 Although study results vary, surgery for
currently advised indications appears to convey a
significant survival benefit (27–55%) that
becomes apparent only with follow-up for 6
months after the intervention
 During the initial weeks after surgery, mortality

risk is actually increased (disease- plus surgery-
related mortality).
 With less demanding surgical indications, this
combined mortality risk may erode potential long-
term benefits.
 Early surgery- during initial hospitalization before
completion of a full therapeutic course of antibiotics
 Early surgery is indicated for
 IE who present with valve dysfunction resulting in
symptoms of HF
 Left-sided IE caused by S. aureus, fungal, or other
highly resistant organisms
 IE complicated by heart block, annular or aortic
abscess, or destructive penetrating lesions
 Persistent infection as manifested by persistent
bacteremia or fevers lasting longer than 5 to 7 days
after onset of appropriate antimicrobial therapy
SURGERY
Indications for Cardiac Surgical Intervention in Patients with Endocarditis
Surgery required for optimal outcome
Moderate to severe congestive heart failure due to valve dysfunction
Partially dehisced unstable prosthetic valve
Persistent bacteremia despite optimal antimicrobial therapy
Lack of effective microbicidal therapy (e.g., fungal or Brucella endocarditis)
S. aureus prosthetic valve endocarditis with an intracardiac complication
Relapse of prosthetic valve endocarditis after optimal antimicrobial therapy
SURGERY
Indications for Cardiac Surgical Intervention in Patients with Endocarditis
Surgery to be strongly considered for improved outcomea
Perivalvular extension of infection
Poorly responsive S. aureus endocarditis involving the aortic or mitral valve
Large (>10-mm diameter) hypermobile vegetations with increased risk of
embolism
Persistent unexplained fever (10 days) in culture-negative native valve
endocarditis
Poorly responsive or relapsed endocarditis due to highly antibiotic-resistant
enterococci or gram-negative bacillI
Indication for Surgical Intervention
Timing Strong Supporting Evidence Conflicting Evidence, but
Majority of Opinions Favor
Surgery
Emergent Acute aortic regurgitation plus preclosure of
(same day) mitral valve
Sinus of Valsalva abscess ruptured into right
heart
Rupture into pericardial sac
Urgent Valve obstruction by vegetation Major embolus plus persisting
(within 1–2 Unstable (dehisced) prosthesis large vegetation (>10 mm in
days) Acute aortic or mitral regurgitation with heart diameter)
failure (New York Heart Association class III or
IV)
Septal perforation
Perivalvular extension of infection with/without
new electrocardiographic conduction system
changes
Lack of effective antibiotic therapy
Elective Progressive paravalvular prosthetic regurgitation Staphylococcal PVE
(earlier usually Valve dysfunction plus persisting infection after Early PVE (2 months after
preferred) 7–10 days of antimicrobial therapy valve surgery)
Fungal (mold) endocarditis Fungal endocarditis
Antibiotic-resistant org.
SURGERY
 Complete removal of pacemaker or defibrillator

systems, including all leads and the generator
 Documented infection of the device or leads
 S.aureus or fungi, even without evidence of
device or lead infection
 In patients undergoing valve surgery for valvular IE
To cure endocarditis, all bacteria in the vegetation must be
killed. However, it is difficult to eradicate these bacteria
because local host defenses are deficient and because the
bacteria are largely nongrowing and metabolically inactive
and thus are less easily killed by antibiotics. Accordingly,
therapy must be bactericidal and prolonged. Antibiotics are
generally given parenterally to achieve serum concentrations
that, through passive diffusion, result in effective
concentrations in the depths of the vegetation Although
given for several weeks longer, the regimens recommended
for the treatment of PVE (except that caused by
staphylococci) are similar to those used to treat NVE
174
Thus empirical therapy for
acute endocarditis in an injection drug user should cover MRSA and
gram-negative bacilli. Treatment with vancomycin plus gentamicin,
initiated immediately after blood samples are obtained for culture,
covers these organisms as well as many other potential causes.
Similarly, treatment of health care–associated endocarditis must
cover MRSA. In the treatment of culture-negative episodes, marantic
endocarditis must be excluded and fastidious organisms sought
by serologic testing. In the absence of prior antibiotic therapy, it is
unlikely that S. aureus, CoNS, or enterococcal infection will present
with negative blood cultures; thus, in this situation, recommended
empirical therapy targets not these organisms but rather nutritionally
variant organisms, the HACEK group, and Bartonella species.
175
Pending the availability of diagnostic data, blood culture–negative
subacute NVE is treated with gentamicin plus ampicillin-sulbactam
(12 g every 24 h) or ceftriaxone; doxycycline (100 mg twice daily) is
added for enhanced Bartonella coverage. For culture-negative PVE,
vancomycin, gentamicin, cefepime, and rifampin should be used if
the prosthetic valve has been in place for ≤1 year. Empirical therapy
for infected prosthetic valves in place for >1 year is similar to that
for culture-negative NVE. If cultures may be negative because of
confounding by prior antibiotic administration, broader empirical
therapy may be indicated, with particular attention to pathogens
176
CIED Endocarditis Antimicrobial therapy for CIED endocarditis is
adjunctive to complete device removal. The antimicrobial selected
is based on the causative organism and should be used as
recommended
for NVE . Bacteremic CIED infection may
be complicated by coincident NVE or remote-site infection (e.g.,
osteomyelitis). A 4- to 6-week course of endocarditis-targeted
therapy is recommended for patients with CIED endocarditis and for
those with bacteremia that continues during ongoing antimicrobial
therapy after device removal. Although S. aureus bacteremia (and
persistent CoNS bacteremia) in patients who have a CIED in place
is likely—in the absence of another source—to reflect endocarditis
and should be managed accordingly, not all bloodstream infections
in these patients indicate endocarditis
177
. If evidence suggesting
endocarditis is lacking, bloodstream infection due to gram-negative
bacilli, streptococci, enterococci, and Candida species may not indicate
device infection. However, in the absence of another source,
relapse after antimicrobial therapy increases the likelihood of CIED
endocarditis and warrants treatment as such.
Blood cultures should be repeated daily until sterile in patients
with endocarditis due to S. aureus or difficult-to-treat organisms,
rechecked if there is recrudescent fever, and performed again 4–6
weeks after therapy to document cure. Blood cultures become
sterile within 2 days after the start of appropriate therapy when
infection is caused by viridans streptococci, enterococci, or HACEK
organisms
178
. In S. aureus endocarditis, β-lactam therapy results in
sterile cultures in 3–5 days, whereas in MRSA endocarditis, positive
cultures may persist for 7–9 days with vancomycin or daptomycin
treatment. MRSA bacteremia persisting despite an adequate dosage
of vancomycin may indicate infection due to a strain with reduced
vancomycin susceptibility and therefore may point to a need for
alternative therapy. When fever persists for 7 days despite appropriate
antibiotic therapy, patients should be evaluated for paravalvular
abscess, extracardiac abscesses (spleen, kidney), or complications
(embolic events). Recrudescent fever raises the possibility of these
complications but also of drug reactions or complications of
hospitalization.
Vegetations become smaller with effective therapy;
however, 3 months after cure, 50% are unchanged and 25% are
slightly larger
179
ENTEROCOCCI ENTEROCOCCI ARE RESISTANT TO OXACILLIN, NAFCILLIN, AND
THE CEPHALOSPORINS AND ARE ONLY INHIBITED—NOT KILLED—BY PENICILLIN,
AMPICILLIN, TEICOPLANIN (NOT AVAILABLE IN THE UNITED STATES), AND
VANCOMYCIN
To kill enterococci requires the synergistic interaction

of a cell wall–active antibiotic that is effective at achievable serum
concentrations (penicillin, ampicillin, vancomycin, or teicoplanin)
and an aminoglycoside (gentamicin or streptomycin) to which the
isolate does not exhibit high-level resistance. An isolate’s resistance
to cell wall–active agents or its ability to replicate in the presence of
gentamicin at ≥500 μg/mL or streptomycin at 1000–2000 μg/mL—a
phenomenon called high-level aminoglycoside resistance—indicates
that the ineffective antimicrobial agent cannot participate in the
interaction to produce killing. High-level resistance to gentamicin
predicts that tobramycin, netilmicin, amikacin, and kanamycin also
will be ineffective. endocarditis. High concentrations of ampicillin
plus ceftriaxone or cefotaxime, by expanded binding of penicillin-
binding proteins, also kill E. faecalis in vitro and in animal models of
endocarditis.
180
If there is high-level resistance to both gentamicin and
streptomycin, a synergistic bactericidal effect cannot be
achieved by the addition of an aminoglycoside; thus no
aminoglycoside should be given. Instead, an 8- to 12-week
course of a single cell wall–active agent can be considered;
for E. faecalis endocarditis, high doses of ampicillin
combined with ceftriaxone or cefotaxime are suggested.
Nonrandomized comparative studies suggest that ampicillin-
ceftriaxone may be as effective as (and less nephrotoxic
than) penicillin or ampicillin plus an aminoglycoside in the
treatment of E. faecalis endocarditis
181
Staphylococcal PVE is treated for 6–8 weeks with a multidrug
regimen. Rifampin is an essential component because it kills
staphylococci that are adherent to foreign material in a biofilm.
Two other agents (selected on the basis of susceptibility testing)
are combined with rifampin to prevent in vivo emergence of
resistance. Because many staphylococci (particularly MRSA and
Staphylococcus epidermidis) are resistant to gentamicin, the
isolate’s susceptibility to gentamicin or an alternative agent should
be established before rifampin treatment is begun. If the isolate is
resistant to gentamicin, then another aminoglycoside, a
fluoroquinolone (chosen on the basis of susceptibility), or another
active agent should be substituted for gentamicin.
182
Methicillin-susceptible S. aureus endocarditis that is uncomplicated
and limited to the tricuspid or pulmonic valve can often be
treated with a 2-week course that combines oxacillin or nafcillin
(but not vancomycin) with gentamicin. However, patients with
prolonged
fever (≥5 days) during therapy or multiple septic pulmonary
emboli should receive standard-duration therapy. Vancomycin plus
gentamicin for 2 weeks as treatment for right-sided endocarditis
caused by MRSA yields suboptimal results; thus this entity is treated
for 4 weeks with vancomycin or daptomycin (6 mg/kg as a single
daily dose).
183
SURGICAL TREATMENT
I
ndications- no absolute indications
 Intracardiac
 CHF class III or IV(refractory)

 Because of the highly invasive nature of prosthetic valve endocarditis, as many as
40% of affected patients merit surgical treatment.
 moderate to severe heart failure due to valve dysfunction who are treated medically,
60–90% die within 6 months, surgical treatment improves outcome, with mortality
rates of 20% in native valve endocarditis and 35–55% in prosthetic valve infection.
 Surgery can relieve functional stenosis due to large vegetations or restore
competence to damaged regurgitant valves.
 perivalvular infection-
 occurs in 10–15% of native valve and 45–60% of prosthetic valve infections.
• persistent fever
• new ECG conduction disturbance
• pericarditis
• fistula
 Uncontrolled infection
 positive blood culture or persistent fever after effective treatment
 lack of adequate effective treatment( yeasts, fungi, P. erogenous ,Brucella, C. burnetii)
184
 Poorly responsive S. aureus endocarditis involving the aortic or
mitral valve
 Prevention of systemic embolization
TIMING
No delay if indication exists. Neurologic complications of
endocarditis may be exacerbated as a consequence of cardiac
surgery. The risk of neurologic deterioration
is related to the type of neurologic complication and the
interval between the complication and surgery
 Delay in those experienced neurological complication
 hemorrhagic embolic stroke 4 weeks.
 non hemorrhagic embolic stroke 2-3 weeks
A ruptured mycotic aneurysm should be treated before

cardiac surgery
185
Detection of organisms or their DNA does not necessarily indicate
antibiotic failure; in fact, relapse of endocarditis after surgery is
uncommon. Thus, when valve cultures are negative in uncomplicated
NVE caused by susceptible organisms, the duration of preoperative
plus postoperative treatment should equal the total duration
of recommended therapy, with ~2 weeks of treatment administered
after surgery. For endocarditis complicated by paravalvular
abscess, partially treated PVE, or cases with culture-positive valves,
a full course of therapy should be given postoperatively. In patients
with aortic or mitral valve regurgitation or a prosthetic valve,
treatment of acute Q fever with doxycycline plus
hydroxychloroquine for 12 months is highly effective in preventing
C. burnetii endocarditis
186
INDICATIONS FOR CARDIAC SURGICAL INTERVENTION IN PATIENTS WITH ENDOCARDITIS
 Surgery required for optimal outcome

Moderate to severe congestive heart failure due to valve dysfunction
 Partially dehisced unstable prosthetic valve
 Persistent bacteremia despite optimal antimicrobial therapy
 Lack of effective microbicidal therapy (e.g., fungal or Brucella endocarditis)
 S. aureus prosthetic valve endocarditis with an intracardiac complication
 Relapse of prosthetic valve endocarditis after optimal antimicrobial therapy
 Surgery to be strongly considered for improved outcome

 Perivalvular extension of infection
 Poorly responsive S. aureus endocarditis involving the aortic or mitral valve
 Large (>10-mm diameter) hypermobile vegetations with increased risk of
embolism
 Persistent unexplained fever (10 days) in culture-negative native valve
endocarditis
 Poorly responsive or relapsed endocarditis due to highly antibiotic-resistant
enterococci or gram-negative bacilli
187
COMPLICATIONS
CARDIAC EXTRACARDIAC
 Heart Failure  Embolization

 Neurologic cxns
 Perivalvular abscess
 Metastatic abscesses
 Pericarditis
 Mycotic aneurysm
 Suppurative or
 Renal
nonsuppurative
 Glomerulonephritis
 Intracardiac fistulas  Embolic infarction
 Eg, aorta-atrial or aorta-  Metastatic abcess
ventricular  Muskuloskeletal cxns
 Vertebral osteomyelitis
 Septic arthitis
COMPLICATIONS- EMBOLIZATION
 Any blood vessel, large or small, in the systemic
or pulmonary arterial circulation can be involved
producing
 Stroke
 Blindness
 Painful ischemic or frankly gangrenous extremities
 Unusual pain syndromes (eg, due to splenic or
renal infarction)
 Hypoxia (due to pulmonary emboli in right-sided
endocarditis)
 Paralysis (due to embolic infarction of either the
brain or spinal cord)
 Acute myocardial infarction
COMPLICATIONS- NEUROLOGIC
 The mechanism for and types of neurologic
complications are diverse and include:
 Embolic stroke
 Acute encephalopathy
 Meningoencephalitis
 Purulent or aseptic meningitis
 Cerebral hemorrhage (due to stroke or a ruptured
mycotic aneurysm)
 Brain abscess or cerebritis
 Seizures (secondary to abscess or embolic
infarction)
COMPLICATIONS- METASTATIC ABSCESS
 Metastatic Abscess
 Can develop in the kidneys, spleen, brain, or soft
tissues (e.g., the psoas muscle) in the setting of
infective endocarditis
 Splenicabscess in 3–5% of patients with

endocarditis.
 Effective therapy requires either image-guided
percutaneous drainage or splenectomy.
COMPLICATIONS- MYCOTIC ANEURYSMS
 Occur in 2–15% of endocarditis patients
 Both cerebral and systemic arteries can be involved
 50%- cerebral arteries and present as headaches,

focal neurologic symptoms, or hemorrhage.
 Cerebral aneurysms should be monitored by angiography.
 Some will resolve with effective antimicrobial therapy,
but those that persist, enlarge, or leak should be
treated surgically if possible.
 Extracerebral aneurysms present as local pain, a

mass, local ischemia, or bleeding; these aneurysms
are treated by resection.
OUTCOME
 Older age, severe comorbid conditions and
diabetes, delayed diagnosis
 Adverse outcomes are associated with the

following conditions
 Involvement of prosthetic valves or the aortic valve,
 An invasive (S. aureus) or antibiotic-resistant (P.
aeruginosa, yeast) pathogen,
 Intracardiac and major neurologic complications, and
 An association with health care
OUTCOME
 Overall survival rates for patients with NVE
caused by viridans streptococci, HACEK
organisms, or enterococci (susceptible to
synergistic therapy) are 85–90%.
 The in-hospital mortality rate for IE is high, at 15% to

20%, with 1-year mortality approaching 40%.
 Death and poor outcome often are related not to failure of
antibiotic therapy but rather to the interactions of
comorbidities and endocarditis-related end-organ
complications
OUTCOME
 For S. aureus NVE in patients who do not inject
drugs, survival rates are 55–70%
 Whereas 85–90% of injection drug users survive

this infection.
 PVE beginning within 2 months of valve

replacement results in mortality rates of 40–
50%, whereas rates are only 10–20% in later-
onset cases.
PREVENTION
 American Heart Association and the European
Society of Cardiology now recommend
prophylactic antibiotics only for those patients
at highest risk for severe morbidity or death
from endocarditis
 Maintaining good dental hygiene is essential.

 Prophylaxis is recommended only when there is
manipulation of gingival tissue or the periapical
region of the teeth or perforation of the oral
mucosa (including surgery on the respiratory tract).
PREVENTION
 Prophylaxis is not advised for patients
undergoing gastrointestinal or genitourinary
tract procedures.
 High-risk patients should be treated before or

when they undergo procedures on an infected
genitourinary tract or on infected skin and soft
tissue
PREVENTION
 The British Society for Antimicrobial
Chemotherapy continues to recommend
prophylaxis for at-risk patients undergoing
selected gastrointestinal and genitourinary
procedures
 In contrast, the National Institute for Health

and Clinical Excellence in the United Kingdom
found no convincing evidence that antibiotic
prophylaxis was cost effective and advised
discontinuation of the practice
PREVENTION
High-Risk Cardiac Lesions for Which Endocarditis Prophylaxis Is
Advised before Dental Procedures
Prosthetic heart valves
Prior endocarditis
Unrepaired cyanotic congenital heart disease, including palliative
shunts or conduits
Completely repaired congenital heart defects during the 6 months
after repair
Incompletely repaired congenital heart disease with residual defects
adjacent to prosthetic material
Valvulopathy developing after cardiac transplantation
PREVENTION
Antibiotic Regimens for Prophylaxis of Endocarditis in Adults with
High-Risk Cardiac Lesions
A. Standard oral regimen
1. Amoxicillin: 2 g PO 1 h before procedure
B. Inability to take oral medication
1. Ampicillin: 2 g IV or IM within 1 h before procedure
C. Penicillin allergy (all 1h before procedure)
1. Clarithromycin or azithromycin: 500 mg PO
2. Cephalexinc: 2 g PO
3. Clindamycin: 600 mg PO
D. Penicillin allergy, inability to take oral medication
1. Cefazolinc or ceftriaxonec: 1 g IV or IM 30 min before procedure
2. Clindamycin: 600 mg IV or IM 1 h before procedure
THANK YOU!

Infective Endocarditis

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Infective Endocarditis

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INFECTIVE ENDOCARDITIS

The analogous process involving arteriovenous shunts,

 Endocarditis may be classified according to the

 Subacute endocarditis follows an indolent course;

 In these countries, predisposing factors are

 30–35% of cases of native valve endocarditis

 16–30% of all cases of endocarditis involve

 The overall distribution of infecting organisms

 The viridians group includes several evolving species of

abscess formation and metastatic infection foci, both within

 For Gemella, one species designated as morbillorum

 These organisms can cause IE and exhibit metabolic

 Similarto other bacteria, viridans group streptococci

the definitions used to characterize strains as being

penicillin-resistant are not the same as the breakpoints

 Injection drug users and elderly persons are two at-

 Complications are frequent and often involve valve

 The prevalence of beta-hemolytic streptococci among

 Nevertheless, it is prudent to obtain susceptibility

 Surgery is often required for management of severe

 Although it continues to be a common cause of

 When it does cause IE, the clinical presentation

 Invasive isolates of pneumococci tend to be

 As with IE due to beta-hemolytic streptococci,

 Unfortunately, the rate of IE due to S. aureus is

 In addition, resistance to oxacillin and other

 They also can cause native valve infection in a

 Although these infections usually are subacute in

 Staphylococcus epidermidis is the most commonly

 Staphylococcus lugdunensis is another species that causes

A majority of infections are due to Enterococcus

 More recently, enterococcal species associated with

 With this group of organisms, a subacute IE

 This includes infection due to vancomycin-resistant

actinomycetemcomitans), & Aggregatibacter aphrophilus (formerly

 Kingella kingae, and Kingella denitrificans

 Accounts for approximately 5%-10% of community-acquired

 As a result, embolism to the brain or other systemic

 This group includes Escherichia coli, Klebsiella

 IE can be either community- or health care–

 Outcomes of IE due to aerobic gram-negative bacilli

 Identification of these organisms often is difficult,

 Even when selected culture media are used, fungal

 Thus fungi can cause either blood culture–positive or

 Complications are frequent, and surgical intervention

 Because relapsing IE is a concern and can be delayed

 In one-third to one-half of these cases, cultures are

 The remainder of these patients are infected by

 In the latter, blood cultures can be held for an extended

 Other techniques, such as special culture methods or serologic

 Prosthetic valve endocarditis (PVE) arising within

 The portals of entry and organisms causing cases

 Regardless of the time of onset after surgery,

 Left-sided valve infections in addicts have a

2. Infection may involve normal valves

 The endothelium, unless damaged, is resistant to

 Endothelial injury allows either direct infection by

 The cardiac conditions most commonly resulting in

 Bland vegetations complicating systemic lupus

 Except for more virulent bacteria (e.g., S. aureus)

 The microbiologic and histopathologic findings in

 In addition, animals do not develop experimental

 Fibrin deposition combines with platelet