Infective endocarditis, a microbial
infection of the endocardial surface of the heart has been classified
as "acute" or "subacute-chronic" on the basis of the tempo and
severity of the clinical presentation and progression of the
untreated disease. The characteristic lesion, the vegetation,
is composed of a collection of platelets, fibrin, microorganisms,
and inflammatory cells. It most commonly involves heart valves
but may also occur at the site of a septal defect, on the chordae
tendineae, or on the mural endocardium.
This report will focus on progress
made over the last decade in the diagnosis and management of
endocarditis affecting native and prosthetic valves in adults.
EPIDEMIOLOGIC FEATURES
AND PREDISPOSITION FACTORS
Infective Endocarditis of Native
Valves
The epidemiologic features of
infective endocarditis in developed countries are changing as
a result of increasing longevity, new predisposing factors,
and an increase in nosocomical cases. In the United States and
western Europe the incidence of community-acquired native- valve
endocarditis in most recent studies is 1.7 to 6.2 cases per
100,000 person-years. Men are more often affected than women
(mean male- to-female ratio, 1.7 to 1. as increasing longevity
has given rise to degenerative valvular disease, placement of
prosthetic valves, and increased exposure to nosocomial bacteremia,
the median age patients has gradually increased; it was 30 to
40 years during the preantibiotic era and 47 to 69 years more
recently. Among patients with infective endocarditis associated
with injection-drug use, there is a trend toward younger persons.
The incidence of infected endocarditis in this group is estimated
at 150 to 2000 per 100,000 person-years and can be higher among
patients with known valvular heart disease.
Other conditions associated
with an increased incidence of infective endocarditis include
poor dental hygiene, long term hemodialysis , and diabetes mellitus.
Infection with the human immunodeficiency virus (HIV) may independently
increase the risk of infected endocarditis. However, among patients
infected with HIV, infective endocarditis is usually associated
with injection-drug use or long term indwelling intravenous
catheters. Staphylococcus aureus is the most frequent pathogen
in these patients, and mortality is higher among those with
advanced HIV disease.
Mitral-valve prolapse is now
the most common cardiovascular diagnosis predisposing patients
to infective endocarditis; the frequency of mitral-valve prolapse
in patients with infective endocarditis is more reflective of
the high frequency of this lesion in the general population
than of the small to moderate increase in the intrinsic rate
of infection associated with this lesion. The incidence of infective
endocarditis in persons with known mitral-valve prolapse is
approximately 100 per 100,000 patient-years; the risk may be
higher in men over 45 years of age. Risk factors for infective
endocarditis in patients with mitral-valve prolapse include
the presence of mitral regurgitation or thickened mitral leaflets.
In developed countries, rheumatic heart disease, which occurs
primarily among the young, remains the most frequent underlying
cardiac condition predisposing patients to infective endocarditis.
Infective Endocarditis of Prosthetic
Valves
Prosthetic-valve endocarditis
accounts for 7 to 25% of cases of infective endocarditis in
most developed countries. In metropolitan Philadelphia, for
example, the frequency of infective endocarditis involving prosthetic
valves was 0.94 per 100,000 patient-years although the mechanical
heart valves are probably at higher risk for infection than
are bio prostheses during the first three months after surgery,
the rates of infection for the two valve types converge later
and are similar at five years. In 1985 it was reported that
the cumulative risk of prosthetic- valve endocarditis as 3.1
% at 12 months and 5.7 % at 60 months after surgery. In more
recent studies,this risk was approximately 1% at 12 months and
2 to 3 % at 60 months.
Cases with onset within two months
after surgery are called early prosthetic-valve endocarditis
and are usually acquired in the hospital. Cases that occur more
than 12months after surgery are called late prosthetic-valve
endocarditis and largely community acquired. Cases occurring
between 2 and 12 months after surgery are a mixture of hospital
acquired episodes caused by less virulent organisms and community
acquired episodes.
Nosocomial Infective Endocarditis
In some series 70 to 29 % of
all cases of endocarditis seen in tertiary care hospitals are
nosocomial. Infected intravascular devices give rise to at least
half these cases. Other sources of nosocomial infective endocarditis
include genitourinary or gastrointestinal tract procedures or
surgical wound infection.
MICROBIOLOGIC FEATURES
In recent series, staphylococci,
particularly Staph.aureus, have surpassed viridans streptococci
as the most common cause of infective endocarditis ( table
1). In addition, coagulase-negative staphylococci, the most
common pathogens in early prosthetic-valve endocarditis, have
also been well documented as an occasional case of native valve
endocarditis. One species of community-acquired coagulase negative
staphylococcus, Staph.lugdunensis, is commonly associated with
valve destruction and the requirement for valve replacement.
The most common streptococci isolated from patients with endocarditis
continue to be Streptococcus sanquis, Strep. bovis, Strep. mutans,
and Strep. mitis. Infective endocaditis caused by Strep. bovis
is prevalent among the elderly and is associated with preexisting
colonic lesions. Enterococci are frequently implicated in nosocomial
bacteremias and is infective endocarditis that is resistant
to medical therapy. However, enterococcal endocarditis is much
less common than in enterococcal bacteremia; the frequency of
infective endocarditis is less than 10% among patients with
enterococcal bacteremia. Polymicrobial infective endocarditis
although still uncommon is encountered most often in association
with injection-drug use.
New diagnostic ,approaches including
culture and microbiological assessment of vegetations, have
yielded a better understanding of blood culture- negative infective
endocarditis.Only 5 to 7 % of patients who have been given a
diagnosis of infective endocarditis according to strict criteria
and who have not recently received antibiotics will have sterile
blood cultures. For example, blood cultures were negative in88
of 620 cases(14%) of infective endocarditis documented in France
during a one- year nation wide survey. In 42 of 88 cases, negative
cultures were associated with the administration of antibiotics
before blood was drawnfor culture. Suppression of bacteremia
often persist longer than the antibiotic is present in theblood.
Such suppression can be countered in patients with subacute
endocarditis by delaying empirical therapy and by obtaining
additional blood cultures.
The polymerase chain reaction
can be used to identify uncultural organisms in excised vegetations
or systemic emboli. This approach has been used to diagnose
infective endocarditis due to Tropheryma whipplei and bartonella
speices and is a promising tool for establishing a microbiological
diagnosis in selected patients with blood -culture- negative
infective endocarditis.
When blood culture from patients
with suspected infective endocarditis remain sterile after 48
to 72 hours of incubation, the clinical must advise the laboratory
of the suspected diagnosis. This will allow the laboratory,
if blood cultures remain negative after 5 to 7 days, to intensify
efforts to recover fastidious organisms and initiate serologic
assessment of causation. These efforts could include prolonged
incubation and in the plating of subcultures on more enriched
mediums. Use of the lysis centrifugation system for blood cultures
allows direct planting to special supportive mediums with the
potential to increase the speed of recovery of more fastidious
organisms. In table
2 some of the most common causes of blood- culture- negative
infective endocarditis and approaches to diagnosis are summarized.
CLINICAL MANIFESTATIONS
The presentation of infective
endocarditis often includes extracardiac manifestations or findings
that are associated with intracardiac extension of infection.
Fever is the most common symptom and sign; however it may be
absent or minimal in patients with congestive heart failure,
severe debility chronic renal or liver failure, previous use
of antimicrobial drugs or infective endocarditis caused by less
virulent organisms. Other common symptoms of acute infective
endocarditis include anorexia, weight loss, malaise and night
sweats. Most patients with infective endocarditis have a heart
murmur ( most commonly preexisting), and patients may have petechiae
on the skin , conjunctinae, or oral mucosal mucosa ,as well
as splenomegaly and other peripheral manifestations (Fig.
201a). Prosthetic- valve endocarditis may be manifested
as an indolent illness with low grade fever, or it can be an
acute febrile, toxic illness. The high frequency of invasive
infection in prosthetic-valve endocarditis results in higher
rates of new or changing murmurs and of congestive heart failure.
Unexplained fever in patient with the prosthetic valve should
prompt careful evaluation for prosthetic-valve endocarditis.
Isolated right sided infective endocarditis is not associated
with peripheral emboli and other peripheral vascular phenomena:
instead, pulmonary findings may predominate.
The onset of nosocomial infective
endocarditis is usually acute, and signs of endocarditis are
infrequent.The diagnosis of infective endocarditis is suggested
by bacteremia persisting for days before treatment or for 72
hours or more after the removal of an infected catheter and
the initiation of treatment, especially in patient with an abnormal
or prosthetic valve.Among patients with the prosthetic valves
or candidemia from sources other than valves carries risks of
subsequent prosthetic-valve endocarditis of approximately 16%
and and 11%, respectively.
DIAGNOSIS
The diagnosis of infective endocarditis
requires the integration of clinical laboratory and echocardiographic
data. Nonspecific laboratory abnormalities may be present including
anemia.leukocytosis, abnormal urinaysis results and an elevated
sedimentation rate and C- reactive protein level. Patients with
suspected infective endocarditis should have electrocardiogram
perfomed on admission( and repeated during their course as appropiate
). New atrioventricular, fascicular, or bundle branch block,
particularly in the setting of aortic- valve endocarditis, suggests
privavular invasion, and such patients may need cardiac monitoring
until they are stable. New atrioventricular block carries a
moderately high positive predictive value for the formation
of a myocardial abscess, but the sensitivity is low.
The Duke Criteria
In 1994, a group at Duke University
proposed standardized criteria for assessing patients with suspected
infective endocarditis. these criteria integrated factors predisposing
patients to the development of infective endocarditis, the blood
culture isolate and persistence of bacteremia, and echocardiographic
findings with other laboratory and clinical information. The
usefulness of these Duke criteria in assessing patients with
potential infective endocarditis have been validated in several
subsequent studies. The specificity of the initially proposed
criteria(the ability to reject the diagnosis correctly) was
high (0.99, with a 95% confidence interval of 0.97 to 1.0) and
the negative predictive value was greater than 92%. Also, a
retrospective study of 410 patients with diagnosed endocarditis
found that the Duke criteria had good (72 to 90 percent) agreement
with clinical assessment of infectious-disease experts. Most
discrepancies occurred when the experts rejected cases categorized
as possible endocarditis according to the Duke criteria. Misclassification
of the culture- negative cases, the increasing role of transesophogeal
echocardiography, the relative risk of endocarditis in Staph.aureus
bacteremia and the overly broad categorization of cases as "possible"
were problems with the original criteria. A modified version
of Duke criteriapont terrier has recently been proposed (table
3).
Echocardiography
Transthoracic echocardiography
is rapid and noninvasive and has excellent specificity for vegetations
(98%). However, transthoracic echocardiography may be in- adequate
in up to 20 percent of adult patients because of obesity, chronic
obstructive pulmonary disease, or chest wall deformities; the
overall sensitivity for vegetations may be less than 60 to 70%.
Transesophageal echocardiography
(see video 1, 2,
3, and picture
1) is more costly and invasive but increases the sensitivity
for detecting vegetations to 75 to 95 percent while maintaining
specificity and 85 to 98 percent. Panel A and Video Clip 1 show
a large area of vegetation (VEG, arrow in Panel A) on the anterior
mitral valve (AMV), seen on the midesophageal four-chamber view.
PMV denotes posterior mitral valve, and TV tricuspid valve.
Panel B and Video Clip 2 of the Supplementary Appendix show
a perforation (arrow in Panel B) of the right aortic valve (AV)
leaflet and an abscess (triangles in Panel B) of the anterior
aortic (Ao) root, seen on the midesophageal short-axis view
of the aortic root. Panel C and Video Clip 3 of the Supplementary
Appendix show a color Doppler study of a posteriorly directed
jet of aortic regurgitation (AR, arrow in Panel C) against the
anterior mitral leaflet. AoR denotes aortic root, and LVOT left
ventricular outflow tract. A pulsed Doppler study (Panel D)
shows the pan-diastolic flow reversal (arrows) in the distal
ascending aorta. The scale to the right indicates flow velocity
measured in centimeters per second, the signal above the baseline
indicates forward flow, and the signal below the baseline indicates
reverse flow.
Transesophagealent echocardiography
is particularly useful in patients with Prosthetic valves and
for the valuation of myocardial invasion. A negative transesophageal
echocardiogram has a negative predictive value for infective
endocarditis of over 92%.
Recent guidelines suggest that
among patients with suspected infective endocarditis transthoracic
echocardiography should be used in the valuation of those with
native valves who are good candidates for imaging. In fact,
the appropriate use of echocardiography depends on the prior
probability of infective endocarditis. If this probability is
less than 4 percent, a negative transthoracic echocardiogram
is cost effective and clinically satisfactory in ruling out
infective endocarditis. For patients whose prior probability
of infective endocarditis is 4 to 60 percent, initial use of
a transesophageal echocardiography is more cost effective and
diagnostically efficient than initial use of transthoracic echocardiography,
which, if negative, is followed by a transesophageal echocardiography.
This category of intermediate prior probability includes patients
with unexplained bacteremia with a gram positive coccus, those
with catheter-associated Staph.aureus bacteremia, and those
admitted with fever or bacteremia in the setting for recent
injection-drug use.
Clinical diagnosis of perivavular
extension of infective endocarditis is imprecise. Persistent
bacteremia or fever, recurrent emboli, heart block, congestive
heart failure or a new pathological murmur in a patient with
infective endocarditis may suggest such extension. Transesophageal
echocardiography is more sensitive than transthoracic echocardiography
for defining perivalvular extension of the infective endocarditis
and the presence of a myocardial abscess. Transesophageal echocardiography
with spectral and color-flow Doppler techniques can also demonstrate
the distinctive flow patterns of fistulas, pseudo aneurysms,
ruptured abscess cavities and is more sensitive than transthoracic
echocardiography for identifying valve perforations.
Patients with Staph. aureus Bacteremia
The prevalence of endocarditis
among patients with Staphylococcus aureus bacteremia is variable.
In a study that included 103 patients with fever and Staph.
aureus bacteremia, all of whom underwent both transthoracic
and transesophageal echocardiography, infective endocarditis
was diagnosed in 25 percent of all patients (and in 23 % of
69 intravenous-catheter-associated infection). Among another
262 patients with staphylococcus aureus bacteremia 34 (13%)
were found to have definite infective endocarditis and the frequency
of infective endocarditis was similar whether or not bacteremia
was associated with an intravascular catheter. Factors associated
with an increased probability of infective endocarditis in patients
with Staph. aureus bacteremia include community acquisition,
absence of a primary focus, presence of metastatic sequelae,
and fever or bacteremia persisting for more than three days
after the removal of the catheter. Although these risk factors
are useful clinical aids, recent studies suggest that the use
of transesophageal echocardiogram to determine the appropriate
duration of therapy in patients with uncomplicated, intravascular
-catheter- associated Staph.aureus bacteremia may be a more
cost effective approach than an empirical choice of either two
to four weeks of therapy.
COMPLICATIONS
Cardiac Complications
Congestive heart failure and
neurologic events have the greatest influence on the prognosis
of infective endocarditis. The usual cause of congestive heart
failure in patients with infective endocarditis is infective-induced
valvular damage. Rarely, embolism of fragments of vegetations
can cause acute myocardial infarction and subsequent congestive
heart failure. Aortic-valve infection is more frequently associated
with congestive heart failure than is mitral valve infection.
Extension of infective endocarditis
beyond the valve annulus predicts higher mortality , the more
frequent development of congestive heart failure, and the need
for cardiac surgery. Extension of infection into the septum
may lead to atrioventricular, fascicular, or a bundle-branch
block. Erosion of a mycotic aneurysm of the sinus of Valsava
can cause pericarditis, hemopericardium and tamponade, or fistula
to the right or left ventricle. Pericarditis can also occur
as a complication of myocardial infarction due to coronary-artery
embolization.
Neurologic Complications
Up to 65 percent of embolic
events in infective endocarditis involve the central nervous
system, and neurologic complications develop 20 to 40 percent
of all patients with infective endocarditis. A stroke syndrome
in a patient with fever and underlying valvular heart disease
suggests the possibility of infective endocarditis. The rate
of embolic events in patients with infective endocarditis decreases
rapidly after the initiation of effective antibiotic therapy,
from 13 per thousand patient-days during the first week of therapy
to fewer than 1.2 per 1,000 patient-days after two weeks of
therapy. Mycotic aneurysms result from septic embolization of
vegetations to the arterial vasa vasorum or the intraluminal
space, with subsequent spread of infection through the intima
and vessel wall. Arterial branching points favor the impaction
of emboli and are the most common sites of mycotic aneurysms.
The clinical presentation of patients with intracranial mycotic
aneurysms is quite variable. Some intracranial leak slowly before
rupture and produce headache and mild meningeal irritation,
whereas in other patients, there are no clinically recognized
premonitory findings before sudden intracranial hemorrhage.
Imaging procedures to detect intracranial aneurysm may be useful
in patients with localized to severe headaches ,meningitis with
negative cultures ,or focal neurological signs. Contrast-enhanced
computed tomography (CT )or MRI may provide useful information;
these techniques have approximately 90 to 95 percent sensitivity
for intracerebral bleeding and may identify the location of
an aneurysm. Magnetic resonance angiography is a promising new
technique for the detection of intracranial mycotic aneurysms
but its sensitivity for aneurysms smaller than 5mm is inferior
to that of conventional four-vessel cerebral angiography, which
remains the standard for evaluation .
Systemic Emboli and Splenic Abscess
Systemic embolism is a frequent
complication of infective endocarditis andmost commonly involves
the sleen the kidney, the liver, and the iliac or mesenteric
arteries. Splenic abscess may develop from bacteremic seeding
of a previously infarcted area or direct seeding of the spleen
by an infected embolus. Splenic abscess can be a cause for prolonged
fever and may cause diaphragmatic irritation with pleuritic
or left shoulder pain; abdominal pain and splenomegaly may be
absent. Abdominal C T and MRI appear to be the best tests for
the diagnosis of splenic lesions each with a sensitivity and
specificity 90 to 95 percent .
Prolonged Fever
Fever associated with infective
endocarditis often resolves within two to three days after the
start of appropriate antimicrobial treatment in patients with
less virulent pathogens, and defervescence occurs in 90 percent
of patients by the end of the second week of treatment. The
most common causes of persistent fever (more than fourteen days)
are the extension of infection beyond the valve (often with
myocardial abscess) focal metastatic infection, drug hypersensitivity
(particularly if the fever resolves and recurs), or a nosocomial
infection or other complication of hospitalization such as pulmonary
embolism.
TREATMENT
Choice of Antimicrobial Agents
Treatment of the most common causes of infective endocarditis
is summarized in table 4.
Prolonged parenteral administration of a bactericidal antimicrobial
agent or combination of agents is currently recommended. Treatment
is usually begun in the hospital, but it is often completed
on an outpatient basis once the fever has resolved and follow-up
blood cultures are negative, as long as indications for cardiac
surgery are not present.
The optimal therapy for infective
endocarditis resulting from less common causes is still not
adequately defined. Aminoglycosides and flouroquinolones are
bactericial for bartonella species. However, most patients with
reported cases of infective endocarditis due to bartonella species
has been treated with a beta-lactum antibiotic and an aminoglycoside.
Most patients with infective endocarditis due to bartonella
have also required valve- replacement surgery for cure. Doxycycline
with a second antimicrobial agent, often given for three of
four years until IgG antibody titers drop below 1 to 400, has
been the recommended treatment for infective endocarditis due
to Q fever. A prospective study among 35 patients with Q fever
infective endocarditis suggested that the combination of doxycycline
and hydroxychloroquine (median duration, 26 months ) was associated
with a lower rate of relapse than was therapy with doxycycline
and a fluoroquinolone for a medium of 60 months. Eradication
of Q fever infective endocarditis usually requires valve- replacement
surgery, although relapse of infection on the replaced valve
may occur.
In the absence of clinical clues
to a specific cause,therapy for culture- negative native valve
endocarditis should be individualized and generally includes
penicillin, ampicillin ,ceftriaxone,or vancomycin in combination
with an aminoglycoside. Therapy for culture- negative prosthetic-valve
endocarditis within the initial twelve months after valve replacement
includes at least vancomycin and gentamicin.For patients with
prosthetic-valve endocarditis that begins to twelve months more
after valve surgery, ceftriaxone or cefotaxime self could be
added to cover for HACEK organisms(Haemophilus parainfluenzae,
H.aphrophilus, and H.paraphrophilus, Actinobacillus actinomycetemcomitans,Cardiobacterium
hominis,Eikenella corrodens,and Kingella Kingae). If fevery
due to infective endocarditis persist after empirical therapy,
vale-replacement surgery for debridement and to obtain material
for microbiologic and pathologic evaluation may be considered.
Antimicrobial- Susceptibility
Testing
Determination of minimal inhibitory
concentration ( M I C) of penicillin is necessary to define
optimal therapy for streptococcal infection (table4).
Susceptibility of staphylococci should be determined for oxacillin
(or methicillin), vancomycin, rifampin, gentamicin (or an alternative
aminoglycoside). Strains of staphococci that are resistant to
oxacillin(or methicillin) are cross resistant to all beta-lactum
antibiotics, regardless of the results of in vitro antimicrobial
susceptibility testing. Optimal therapy for enterococcal infective
endocarditis requires a synergistic bactericidal combination
of a cell-wall-active antimicrobial agent to which the organism
is susceptible (penicillin, ampicillin, or vancomycin) plus
an aminoglycoside. Susceptibility testing of enterococci from
patients with infective endocarditis should include determination
of the MICs of penicillin (or ampicillin) and vancomycin and
evaluation for the presence of high level resistance to both
gentamicin and streptomycin. Optimal synergistic antimicrobial
terribly is not available for strains of enterococci with high
level resistance to both gentamicin and streptomycin; therapy
for infective endocarditis due to such organisms (or organisms
highly resistant to penicillin or ampicillin and resistant to
vancomycin) should be developed in consultation with an infectious
disease specialists. Because of the frequency of adverse events
in patients treated for infective endocarditis and the associated
need to revise therapy, the causation organism should ideally
be retained until cure has been ensured. In addition, to ensure
optimal therapeutic regimen, organisms recovered from surgical
specimens or blood cultures at relapse should be studied for
antimicrobial susceptibility.
Anticoagulant Therapy
Anticoagulant therapy has not
been shown to prevent embolization in infective endocarditis
and may increase the risk of intracerebral hemorrhage. Anticoagulant
therapy for native- valve endocarditis is restricted to patients
with a clear indication separate from infective endocarditis;
in the presence of intracranial hemorrhage or mycotic aneurysm,
anticoagulant therapy should be suspended until the complications
have resolved. In general patients with infective endocarditis
involving a prosthetic heart valve that requires maintenance
anticoagulant therapy are cautiously given continued anticoagulant
therapy during treatment of prosthetic-valve endocarditis. However,
in the presence of central nervous system emboli with hemorrhage,
temporary discontinuation of anticoagulant therapy is appropriate.
Patients with Staph.aureus prothestic-valve
endocarditis ff warriors Prosthetic-valve endocarditis who are
receiving anticoagulant therapy are particularly susceptible
to central nervous system hemorrhage; indirect evidence from
uncontrolled studies in a limited number of patients suggests
that anticoagulant therapy should generally be suspended in
such petitions during the acute phase of the illness. If cardiac
surgery for infective endocarditis is planned, warfarin may
be discontinued and replaced with heparin to allow more rapid
reversal ofanticoagulation at the time of surgery. The role
(if any ) of aspirin in the prevention of embolism in infective
endocaditis is still under evaluation.
Surgical Therapy
Several studies suggest that
combined medical and surgical therapy for infective endocarditis
can decreased mortality among patients who have congestive heart
failure, perivalvular invasive disease, or uncontrolled infection
despite maximal antimicrobial therapy; congestive heart failure
is the strongest indication of surgery in infective endocarditis.
For example, medically treated patients with moderate to severe
congestive heart failure due to endocarditis-related valvular
dysfunction have the mortality rate of 56 to 86% as compared
with 11 to 35 % among patients treated with combined medical
and surgical therapy.The hemodynamic status of the patient at
the time of valve-replacement surgery is the principal determinant
of operative mortality; the optimal time to perform surgery
is before severe hemodynamic disability or spread of the infection
to perivalvular tissue has occurred. Serial echocardiograms
may be helpful to monitor the need for valve- replacement surgery.
In some patients the presence of metastatic infection may need
to be assessed before valve- replacement surgery so as to avoid
relapse of infection on the prosthetic valve that is seeded
from these sites.
Medical therapy for infective
endocarditis caused by some microorganisms is usually unsuccessful,
and surgical therapy is generally advised. These pathogens include
pseudomonas aeruginosa, brucella species, Coxiella burnetti,
candida species, other fungi, and probably enterococci for which
there is no synergistic bactericidal regimen. Also, uncontrolled
sepsis in spite of maximal antimicrobial therapy due to any
pathogen is usually an indication for surgery.
Infective-endocarditis involving
a prosthetic valve is another common indication was surgical
evaluation. Patients with prosthetic-valve endocarditis who
can be treated with antimicrobial agents alone are usually characterized
by late onset of infection(more than 12 months after implantation
of a prosthesis); infection by viridans streptococcus, HACEK
organisms or enterococci; and no evidence of perivalvular extension
of infection. Although the rate of recurrent prosthetic-valve
endocaditis after surgery for active infective endocarditis
was up to 7% over a mean follow-up period of six years, there
is no compelling evidence that delaying surgery in patients
with progressive infection or hemodynamic deterioration improves
outcome.
Relapse of prosthetic-valve endocarditis
after appropriate medical therapy should lead to careful echocardiographic
assessment for perivalvular extension of infection or for metastatic
foci of infection such as splenic abscess or osteomylitis. Some
patients with relapsed prosthetic-valve endocarditis may respond
to a second course of antimicrobial therapy, but many such patients
will require combined medical and surgical therapy for cure.
More patients with Staph.aureus prosthetic-valve endocarditis
survive with medical and surgical therapy than with medical
therapy alone ( relative risk of death, 0.18) suggesting that
Staph.aureus prosthetic-valve endocarditis alone may be an indication
for valve replacement surgery.
Some authorities recommend surgery
if there have been two episodeso of embolization or one episode
of residual large vegetations. However , there are no data from
the prospective, controlled trials to support a firm recommendation.
The development of embolic neurologic complications during infective
endocarditis is associated with an increase in mortality by
a factor of two to four. Large vegetations on the mitral-valve,
especially on the anterior leaflet, are associated with a higher
risk of embolism than vegetations of similar size elsewhere.
An increase in the size of vegetations that is detected by echocardiography
during the course of therapy may identify a subgroup of patients
with a higher rate of complications. However, there is no size
or location threshold that suitably predicts increase mortality
associated with embolization is such a way that risk-to-benefit
of surgery for the prevention of embolization can be calculated.
Also, the presence of vegetations as determined by the echocardiography,
is common after successful medical treatment of infective endocarditis
and is not necessarily associated with late complications.The
characteristics of the vegetations alone rarely justify a surgical
intervention; rather data on vegetations should be weighed in
the context of the overall clinical picture to assess the benefits
of surgery. Because of frequency of emboli decreases rapidly
with the effective antimicrobial therapy, the benefit of surgery
in preventing further emboli is greatest if it is performed
early in the course of infective endocarditis.
Because of the potential for
postoperative neurologic deterioration or death, a recent neurological
complication of infective endocarditis has been considered a
relative contraindication to valve- replacement surgery. A retrospective
study of 181 patients with cerebral complications who underwent
surgery for infective endocarditis found that the proportion
of patients who had postoperative neurologic deterioration (
including death) depended on the interval between the preceding
cerebral event and cardiac surgery. Among those who had had
nonhemorrhagic cerebral infarcts 7 days or less before surgery,
neurological deterioration occurred in 44%; among those undergoing
surgery 8 to 14 days after the central nervous system event,
only 16.7% had neurologic deterioration. The risk of a worsening
neurological deficit after cardiac surgery fell to 2.3% when
the operation was performed four weeks or more after the central
nervous system event. However, the risk of a worsening central
nervous system deficit after cardiac surgery persisted for up
to four weeks after intracerebral hemorrhage. In contrast, other
studies have suggested that valve-replacement surgery can be
undertaken with minimal risk of neurological deterioration of
patients who have left sided endocarditis without central nervous
system hemorrhage. A conservative approach is to delay valve-replacement
surgery, if feasible, 2 to 4 weeks after embolic infarct in
the central nervous system and for at least a month after intracerebral
hemorrhage.
The duration of antimicrobial
therapy after valve- replacement surgery for active infective
endocarditis has not been assessed in carefully controlled trials,
but it should depend on the length of preoperative therapy,
the presence of perivalvular extension of infection and the
microbiologic and pathological findings that surgery. The duration
of combined preoperative and postoperative. Therapy for patients
undergoing surgery should be at least as long as that recommended
in table 4. In patients with
a positive intraoperative culture, myocardial abscess ,or a
positive Gram's stain for organisms on a prosthesis removed
from a patient with prosthetic endocarditis , a full course
of postoperative therapy is a reasonable, conservative approach.
MORTALITY AND RELAPSE
The mortality rate among patients
with infective endocarditis varies according to the following
factors: the causative microorganism ( four to 16 sixteen %
for viridans streptococcus and Strep. Bovis, 15 to 25 % for
enterococci, 25% to 47 percent for staph.aureus, 5 to 35 % for
Q fever, and more than 50% percent P.aeruginosa, Enterobacteriacae,
or fungi); the presence of complications or coexisting conditions
( for example, congestive heart failure, neurological events,
renal failure or severe immunosuppression due to HIV infection)
the development of preivalvular extension or the myocardial
abscess; and the use of combined medical and surgical therapy
fair in appropriate patients. The overall mortality rate for
both native-valve and prosthetic-valve remain as high as 25
to 25% with death resulting primarily from central nervous emboli
events and hemodynamic deterioration. The mortality rate for
right-sided endocarditis in injection drug users is generally
lower, approximately 10 percent.
Relapse of infective
endocarditis usually occurs within two months of the discontinuation
of antimicrobial therapy. The relapse rate for patients with
native-valve endocarditis caused by penicillin susceptible viridans
streptococcus who have been treated with one of the recommended
doses of therapy is generally less than 2%.The relapse rate
for the patients with enterococcal native-valve endocarditis
after standard therapy is 8 to 20% among patients with infective
endocarditis caused by Staph. aureus, enterobacteriacae or fungi,
treatment failure often occurs during the primary course of
therapy. A positive culture at the time of valve replacement
surgery, particularly in patients with staphylococcal endocarditis,
is a risk factor for subsequent relapse. The relapse rate in
prosthetic-valve endocarditis is approximately ten to fifteen
percent and relapse of infection may be an indication for combined
medical and surgical therapy.
Mylonakis,E.,and Calderwood,S.B.,N
Engl J Med ,Vol 345,No.18. Nov.1,2001,Pp.1318-1330.
