INFECTIVE ENDOCARDITIS

INTRODUCTION
 Infection most commonly involves heart
valves (either native or prosthetic) but may
also occur on ventricular septal defect
mural endocardium or on intracardiac
devices
 The analogous process involving
arteriovenous shunts, arterioarterial shunts
(patent ductus arteriosus), or a coarctation
of the aorta is called infective endarteritis
 Endocarditis usually occurred more
frequently in men than in women, with a
2:1 ratio
 Pathogenesis
 Disruption of the endocardial layer as
a complication of abnormal blood
flow associated with underlying
cardiac defect
 Bacterium-endothelium interaction
with bacterial attachment and
invasion of endothelial cells
 Infective Endocarditis
 Pathogenesis

Endothelial damage

Platelet-fibrin thrombi

Microorganism adherence
 Infective Endocarditis
 Nonbacterial Thrombotic Endocarditis
 Endothelial injury
Platelet-fibrin thrombi
 Hypercoagulable state
• Lesions seen at coaptation points of valves
 Atrial surface mitral/tricuspid
 Ventricular surface aortic/pulmonic
 Modes of endothelial injury
 High velocity jet
 Flow from high pressure to low pressure chamber
 Flow across narrow orifice of high velocity
• Bacteria deposited on edges of low pressure
sink or site of jet impaction
Venturi Effect
 Conversion of NBTE to IE
 Frequency & magnitude of bacteremia
 Density of colonizing bacteria
 Oral > GU > GI
 Disease state of surface
 Infected surface > colonized surface
 Extent of trauma
 Resistance of organism to host defenses
 Most aerobic gram negatives susceptible to
complement-mediated bactericidal effect of serum
 Tendency to adhere to endothelium
 Dextran producing strep
 Fibronectin receptors on staph, enterococcus,
strep, Candida
 Infective Endocarditis
 Febrile illness
 Persistent bacteremia
 Characteristic lesion of microbial
infection of the endothelial surface of
the heart the vegetation

• Variable in size
• Amorphous mass of fibrin & platelets
• Abundant organisms
• Few inflammatory cells
 EPIDEMIOLOGY
 An estimated 10,000 to 15,000 new cases
of IE are diagnosed in the United States
each year
 IE has increasingly become a disease of the
elderly
 More than one-half of all IE cases in the
United States now occur in patients over the
age of 60
 This trend is probably due to two factors
• the decline in the incidence of rheumatic heart
disease
• the increasing proportion of elderly subjects in
the general population
 CLASSIFICATION (BASED ON TEMPORAL EVOLUTION OF
DISEASE)
 Acute endocarditis: is a hectically febrile
illness that rapidly damages cardiac
structures, hematogenously seeds
extracardiac sites, and, if untreated,
progresses to death within weeks;
 Sub acute 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
CLASSIFICATION (BASED ON PREDISPOSING RISK FACTORS)
1. Native valve endocarditis
 Community acquired
 Health care-associated (nosocomial)
endocarditis: defined as a diagnosis of
IE made more than 72 hours after
admission in patients with no evidence
of IE on admission, or IE developing
within 60 days of a prior admission
when there was a risk factor for
bacteremia or any risk factor for IE
during the hospitalization
2. Prosthetic valve endocarditis
 <2 months
 2-12 months
 >12 months
 RISK FACTORS
 Injection drug use
• Highest risk factor in patients < 40 years of
age
 Prosthetic heart valves
• Prosthetic valve endocarditis comprises a
small but important segment of IE cases
• More than 100,000 heart valves are
implanted annually in the United States
• IE develops in 1 to 4 % of valve recipients
during the 1st year valve replacement, and in
following approximately 1 percent per year
thereafter
 RISK FACTORS
 Nosocomial endocarditis
• Usually a complication of bacteremia induced by
an invasive procedure or a vascular device
 Structural heart disease
• Approximately three-fourths of all patients with
IE have a preexisting structural cardiac
abnormality
• Congenital heart disease is present in 10-20%
cases
• The most common predisposing congenital heart
lesions are bicuspid aortic valves, PDA, VSD,
coarctation of the aorta, and tetralogy of Fallot
 RISK FACTORS
 Degenerative valvular lesions
• The risk of IE in patients with MVP
and associated regurgitation is
estimated to be 5 to 8 times higher
than that in the normal population
• Aortic valve disease(stenosis or/and
regurgitation) is present in 12 to 30
percent of cases
 RISK FACTORS
 History of infective endocarditis
• Recurrent endocarditis occurred in 4.5
percent of one large cohort of non-
addicts
• Other studies have reported rates of IE
recurrence ranging from 2.5 to 9
percent
 HIV infection
• A number of cases of IE have been
reported in patients with HIV infection
• It has been suggested that HIV
infection is an independent risk factor
for IE in IV drug abusers
 A number of other, less common
predisposing factors for IE include
• Pregnancy
• AV fistulas used for hemodialysis
• Central venous and pulmonary artery
catheters
• Peritoneovenous shunts for the control of
ascites
• Ventriculoatrial shunts for the management
of hydrocephalus
 In addition, patients with ulcerative
lesions of the colon due to carcinoma or
inflammatory bowel disease have a
poorly understood predilection to
develop endocarditis secondary to
 Clinical manifestations

• Direct
 Constitutional symptoms of infection
(cytokine)
• Indirect
 Local destructive effects of infection
 Embolization – septic or bland
 Hematogenous seeding of infection
 N.B. may present as local infection or
persistent fever, metastatic abscesses may be
small, miliary
 Immune response
 Immune complex or complement-mediated
 Cont’d
 Local destructive effects
 Valvular distortion/destruction
 Chordal rupture
 Perforation/fistula formation
 Paravalvular abscess
 Conduction abnormalities
 Purulent pericarditis
 Functional valve obstruction
 Cont’d
 Embolization
 Clinically evident 11 – 43% of patients
 Pathologically present 45 – 65%
 High risk for embolization
 Large > 10 mm vegetation
 Hypermobile vegetation
 Mitral vegetations (esp. anterior leaflet)
 Pulmonary (septic) – 65 – 75% of i.v. drug
abusers with tricuspid IE
 Cont’d
 Interval between index bacteremia &
onset of sx’s usually < 2 weeks
 May be substantially longer in early PVE
 Fever most common sign
 May be absent in elderly/debilitated pt.
 Murmur present in 80 – 85%
 Generally indication of underlying lesion
 Frequently absent in tricuspid IE
 Changing murmur
Classical Peripheral Manifestations

 Less common today

 Not seen in tricuspid endocarditis

 Petechiae most common

CLINICAL FEATURES OF IE
 PERIPHERAL MANIFESTATIONS OF IE
 Janeway lesions: are macular, blanching,
nonpainful, erythematous lesions on the
palms and soles
 Osler's nodes: are painful, papulopustular
to violaceous nodular lesions found in the
pulp of fingers and toes and are seen
more often in subacute than acute cases
of IE
 Roth spots are exudative, edematous

hemorrhagic lesions of the retina

 Petechiae

 Splinter hemorrhage: are nonblanching,

Janeway Lesions
Splinter Hemorrhage
Osler’s Nodes
Subconjunctival Hemorrhages
Roth’s Spots
 Clinical Features
 Systemic emboli
 Incidence decreases with effective anti-microbial Rx
 Neurological sequelae
 Embolic stroke 15 – 20% of patients
 Mycotic aneurysm
 Cerebritis
 CHF
 Due to mechanical disruption
 High mortality without surgical intervention
 Renal insufficiency
 Immune complex mediated
 Impaired hemodynamics/drug toxicity
 Diagnosis
 Published criteria for diagnostic

purposes in obscured cases

 High index of suspicion in patients
with predisposing anatomy or
behavior
 Blood cultures
 Echocardiography
• TTE – 60% sensitivity
• TEE – 80 – 95% sensitive
 Case Definition
 Duke criteria
• In 1994 investigators from Duke
University modified the previous
criteria to include the role of
echocardiography in diagnosis
• They also expanded the category of
predisposing heart conditions to
include intravenous drug use
 Duke Criteria
 Definitive infective endocarditis
• pathologic criteria
 microorganisms : demonstrated by
culture or histology in a vegetation, or in
a vegetation that has embolized, or in an
intracardiac abscess or
 Pathologic Lesions : vegetation or
intracardiac abscess, confirmed by
histology
• clinical criteria
 two major criteria, or
 one major and three minor criteria, or
 five minor criteria
 Duke Criteria
 Possible infective endocarditis
• findings consistent of IE that fall short of
“definite”, but not “rejected”
 Rejected
• firm alternate Dx for manifestation of IE
• resolution of manifestations of IE, with
antibiotic therapy for  4 days
• no pathologic evidence of IE at surgery or
autopsy, after antibiotic therapy for  4
days
 Duke Criteria
 Major criteria
• positive blood culture for IE
• evidence of endocardial involvement
 Minor criteria
• predisposition (heart condition or IV drug
use)
• fever of 100.40F or higher
• vascular or immunologic phenomena
• microbiologic or echocardiographic evidence
not meeting major criteria
 Major Criteria
 Positive blood culture for IE
• typical microorganism for IE from two
separate blood cultures in the absence of a
primary focus
 strep viridans, strep bovis, HACEK group,
staph aureus or enterococci
 Persistently positive blood culture
• blood cultures drawn more than 12 hr
apart, or
• all of 3 or a majority of 4 or more separate
blood cultures, with first and last drqwn at
least 1 hr apart
 Major Criteria
 Evidence of endocardial
involvement
• positive echocardiogram for
endocarditis
 oscillating intracardiac mass on valve or
supporting structure, or in the path of
regurgitant jets, or on implanted
material, in the absence of an alternate
anatomic explanation
 abscess
 new partial dehiscence of prosthetic valve
• new valvular regurgitation (increase or
change in pre-existing murmur not
sufficient)
 Minor Criteria
 predisposition
• predisposing heart condition or iv drug use
 fever of 100.40F or higher
 vascular phenomena
• major arterial emboli
• septic pulmonary infarcts
• mycotic aneurysm
• intracranial hemorrhage
• conjunctive hemorrhages
• Janeway lesions
 …. Minor Criteria
 immunologic phenomena
• Glomerulonephritis • Osler’s nodes
• Rheumatoid factor • Roth spots
 microbiologic evidence
• positive blood culture not meeting major
criteria or serologic evidence of active
infection with organism consistent with IE
 echocardiogram
• consistent with IE but not meeting major
criteria
 Validity of Duke criteria
 405 consecutive cases of suspected IE
were studied
 69 cases of IE were confirmed
pathologically
 55 (80 percent) were clinically classified
as definite using the Duke criteria, versus
only 35 being classified as probable by
the von Reyn criteria
 12 of the pathologically confirmed cases
were "rejected" by the von Reyn criteria
whereas none by the Duke criteria
New criteria for diagnosis of infective endocarditis:
Utilization of specific echocardiographic findings.
Duke Endocarditis Service Am J Med 1994;
 Diagnostic approach to infective
endocarditis
 History
• A careful history should be performed with
special attention given to a history of prior
cardiac lesions and historical clues pointing
toward a recent source of bacteremia
 Physical examination
• A meticulous clinical examination should be
performed looking for clinical evidence of small
and large emboli with special attention to the
fundi, conjunctivae, skin, and digits
• Cardiac examination may reveal signs of new
regurgitant murmurs and signs of CHF
 Neurologic evaluation may detect evidence
of focal neurologic impairment
 BLOOD CULTURE
 Blood cultures should be obtained prior to
antibiotic therapy
 Atleast three blood culture sets (with two
bottles per set), separated from each other by
at least 1 h, should be obtained from diff’t
venipuncture sites over 24h
 Each bottle should be inoculated with a
minimum of 10 mL (and preferably 20 mL) of
blood (the estimated yield of blood cultures
in bacteremic adults increased approximately
3 percent per mL of blood cultured)
 Blood cultures can be taken at any time; they
do not need to be obtained with the
appearance of chills or fever since patients
with IE typically have a continuous bacteremia
 From 5 to 15% of patients-negative blood
culture: 1/3-1/2 b/c of prior antibiotic intake
 ADDITIONAL TESTS
 Serologic tests can be used to implicate causally
some organisms that are difficult to recover by blood
culture: Brucella, Bartonella, Legionella, and C.
burnetii
 An elevated erythrocyte sedimentation rate and/or
an elevated level of C-reactive protein
 A normochromic normocytic anemia
 The white blood cell count may be normal or
elevated in patients with subacute presentations of
endocarditis; however, most patients with
staphylococcal endocarditis have leukocytosis and
some may have thrombocytopenia
 Hyperglobulinemia, cryoglobulins, circulating
immune complexes, hypocomplementemia, elevated
rheumatoid factor titers, and false positive serologic
tests for syphilis all occur in some patients
 An abnormal urinalysis, as manifested by microscopic
or gross hematuria, proteinuria, and/or pyuria
 RFT, CXR, CT/MRI scan
 Diagnostic approach to infective
endocarditis

 Electrocardiogram
• All patients with suspected IE should
have an EKG to determine whether
there is evidence of heart block or a
conduction delay and to establish a
baseline should such a complication
develop later
 Diagnostic approach to infective
endocarditis
 Echocardiography
• Should be performed in all patients with
suspected IE
• A TTE should initially be obtained in
patients with native heart valves, while
those with prosthetic valves should
undergo TEE
• Detection of a vegetation by TTE is a
positive test
• However, a negative study does not
preclude the diagnosis and should be
followed by TEE, when there is an
intermediate or high suspicion of IE
 Major Pathogens
 Native Valve IE
• Strep.(55%), mostly
Viridans
• Staph.(30%), mostly
S.aureus
• Late (>60
• Entrococci(5-10%)
days)
 Prosthetic Valve IE  Staph(30%)
• Early (0-2 months)
 Staph(50%)- mostly S.epi.
 IE in IV drug abusers
• Staph. aureus(50-60%)
 Antibiotic Therapy
 Treatment tailored to etiologic agent
• Important to note MIC/MBC relationship
for each causative organism and the
antibiotic used
• High serum concentration necessary to
penetrate avascular vegetation
 Antibiotic Therapy
 Treatment before blood cultures turn
positive
 Suspected ABE
 Hemodynamic instability
• Neither appropriate nor necessary in
patient with suspected SBE who is
hemodynamically stable
 Antibiotic Therapy
 Effective antimicrobial treatment
should lead to defervescence within
7 – 10 days
• Persistent fever in:
 IE due to staph, pseudomonas, culture
negative
 IE with microvascular complications/major
emboli
 Intracardiac/extracardiac septic
complications
 Drug reaction
VIRIDANS STREPTOCOCCI AND STREP. BOVIS
Antibiotic Dosage and route Duration
Aqueous crystalline 12-18 million U/24 h 4 wks
penicillin G sodium IV either continuously
or in 6 = divided doses
or
Ceftriaxone sodium 2g once daily IV or IM 2 wks
Aqueous crystalline 12-18 million U/24 h 2 wks
penicillin G sodium IV either continuously
or in six equally
divided doses
with gentamicin 1 g IM or IV every 8 h 2 wks
sulfate
Vancomycin 30 mg/kg per 24 h IV 4 wks
hydrochloride in two equally divided
doses, not to exceed 2
gram/24h unless serum
levels are monitored
JAMA 1995; 274:1706
Comments
preferred in most patients older than 65 yrs
and in those with impairment of the eighth
nerve or renal function
when obtained 1h after a 20-30 min.
IV infusion or IM injection, serum
concentration of gentamicin of
approximately 3 mcg/mL is desirable;
trough concentration should be < 1 pg/mL
vancomycin therapy is recommended for
patients allergic to beta lactams; peak
serum concentrations of vancomycin should
be obtained one h after completion of the
infusion and should be in the range of
30-45 mcg/mL for twice-daily dosing
ENTEROCOCCI
STAPH. ENDOCARDITIS IN NATIVE VALVES
STAPH. ENDOCARDITIS IN PROSTHETIC VALVES
HACEK ORGANISMS
 Indications for surgery in IE
 The indications for surgery in patients with
native-valve IE and prosthetic-valve IE are
essentially the same
 Surgery is warranted for patients with
active IE who have one or more of the
following complications:
• CHF that is directly related to valve
dysfunction
• Persistent or uncontrolled infection while
receiving appropriate antimicrobial
therapy, including evidence of
perivalvular extension
• Recurrent emboli, particularly in the
presence of large vegetations
 Indications for surgery in IE
 Relative indications for surgery
• Evidence of perivalvular infection, such
as intracardiac abscess or fistula
formation
• Rupture of a sinus of Valsalva aneurysm
• Fungal endocarditis
• Endocarditis due to highly resistant
microorganism
• Relapse after a course of adequate
antimicrobial therapy, particularly in
prosthetic valve endocarditis
• Culture-negative IE with fever more than
10 days after starting empirical therapy
Indications for surgery in prosthetic
valve IE
 Same as native valve endocarditis
 Perivalvular infection
 Valve Dehiscence
• excessively mobile prosthesis on echo
• results in hemodynamic instability
 OUTCOME OF SURGERY
 The outcome of surgery in patients with IE
has been good, particularly when surgical
treatment is radical with the removal of all
infected and necrotic tissue
 In a recent study of 138 patients who
underwent valve surgery in the presence
of active infection, the early mortality, due
to heart failure or septic multiorgan failure,
was 11.5 %
 Risk factors for early mortality were NYHA
class IV or cardiogenic shock, advanced
age, preoperative acute renal failure, and
staphylococcal infection
ACC/AHA recommendation for surgery in patients with
native valve endocarditis
ACC/AHA recommendation for surgery in patients with
prosthetic valve endocarditis
 GENERAL MEASURES FOR THE PREVENTION OF IE

 The incidence of IE can be significantly

reduced by total surgical correction of
some congenital lesions, such as patent
ductus arteriosus, ventricular septal defect,
and pulmonary stenosis
 Maintaining good oral hygiene, which
decreases the frequency of bacteremia that
accompanies daily activities, is an
important preventive measure
 Infections associated with bacteremia must
be treated promptly and, if possible,
eradicated before the involved tissues are
 CHEMOPROPHYLAXIS
 Prophylactic antibiotics are advised only for
those patients at highest risk for severe morbidity
or death from endocarditis
 Prophylaxis is recommended only for dental
procedures wherein 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)
 Although prophylaxis is not advised for patients
undergoing gastrointestinal or genitourinary
tract procedures, it is recommended that
effective treatment be given to these high-risk
patients before or when they undergo
High-Risk Cardiac Lesions for Which Endocarditis Prophylaxis Is
Advised before Dental Procedures
Antibiotic Regimens for Prophylaxis of Endocarditis in Adults
with High-Risk Cardiac Lesions