INFECTIVE ENDOCARDITIS

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 INFECTIVE ENDOCARDITIS
Defn:- It is the proliferation of microorganisms on the
endocardium of the heart.
Infections most commonly involve the heart valve (high
pressure area), either native or prosthetic but can also
involve: -
– the low pressure side ventricular septum at the site of
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.
Classification: -is based on
 Temporal evolution 3
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The acute form follows a fulminant course, usually with high fever,
systemic toxicity, and leukocytosis; death occurs in several days to less
than 6 weeks. It classically is associated with infection caused by
Staphylococcus aureus, Streptococcus pyogenes, Streptococcus
pneumoniae, or Neisseria gonorrhoeae. The subacute form (death
occurring in 6 weeks to 3 months) and the chronic form (death occurring
later than 3 months) usually are considered together. They commonly
occur in the setting of prior valvular disease and are characterized by a
slow, indolent course with low-grade fever, night sweats, weight loss, and
vague systemic complaints. These two forms of IE classically are caused by
the viridans streptococci

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When associated with valvular insufficiency, IE characteristically
occurs on the atrial surface of the mitral valve and the ventricular
surface of the aortic valve. Rodbard showed that this localization is
related to a decrease in lateral pressure (presumably with decreased
perfusion of the intima) immediately downstream from the regurgitant
flow. Lesions with high degrees of turbulence (e.g., small ventricular
septal defect with a jet lesion, valvular stenosis resulting from
insufficient valves) readily create conditions that lead to bacterial
colonization, whereas defects with a large surface area (large ventricular
septal defect), low flow (ostium secundum atrial septal defect),
or attenuation of turbulence (chronic congestive heart failure [CHF]
with atrial fibrillation) rarely are implicated in IE.

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• 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.

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 Classification:
• 1-Acute:
- Aggressive.
- Virulent organisms such as Staph. Aureus.
- Often affects the normal valves.
2- Subacute:
- Indolent course over weeks to months.
- Less virulent organisms such as Strep. Viridans.
- Usually develops on abnormal valves.
3- Early Prosthetic Valve Endocarditis (EPVE):
- Infection of the artificial valves within 2 months after
surgery.
4- Late Prosthetic Valve Endocarditis (LPVE):
-Infection of the artificial valves > 2 months after
surgery.
5- Non - Bacterial Thrombotic Endocarditis (NBTE).
- Any endocardial sterile vegetations – wide spectrum.
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Epidemiology: -
incidence in developed countries is 2.6- 7/100,000 popn/yr.
Men are predominant in most case series, M:F= 2:1-9:1
Incidence is increasing among the elderly.
Rate of prosthetic valve endocarditis is 1.5-3 % in the first year, 3-6 % at 5 year
after replacement
The risk of prosthesis infection is greatest during the first 6 months after valve
replacement; gradually declines to a low, stable rate thereafter; and is similar for
mechanical and bioprosthetic devices.

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In developed
countries, 25–35% of cases of native valve endocarditis (NVE) are
associated with health care, and 16–30% of all cases of endocarditis
involve prosthetic valves. The risk of prosthesis infection 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. The incidence of endocarditis involving cardiovascular
implantable electronic devices (CIED), primarily permanent
pacemakers and implantable cardioverter-defibrillators, ranges
from 0.5 to 1.14 cases per 1000 device recipients and is higher among
patients with an implantable cardioverter-defibrillator than among
those with a permanent pacemaker.

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 Etiology
•The pathogens vary somewhat with the clinical
types of endocarditis, and in part because of
different portals of entry.
•The oral cavity, skin, and URT are the respective
primary portals for the viridans streptococci,
staphylococci, and HACEK organisms causing
community-acquired native valve endocarditis.
•Streptococcus bovis originates from the GIT,
where it is associated with polyps and colonic
tumors
•Enterococci enter the bloodstream from the GUT.
•only a few bacterial species cause the majority of
cases. 13
•
Streptococcus gallolyticus subspecies
gallolyticus (formerly S. bovis biotype 1) originates from the
gastrointestinal tract, where it is associated with polyps and colonic
tumors, and enterococci enter the bloodstream from the genitourinary
tract. Health care–associated NVE, most commonly caused by
Staphylococcus aureus, coagulase-negative staphylococci (CoNS), and
enterococci, may have either a nosocomial onset (55%) or a community
onset (45%); community-onset cases develop in patients who have
had extensive contact with the health care system over the preceding
90 days.

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•Health care–associated native valve
endocarditis is the consequence of
bacteremia arising from IV catheter
infections, nosocomial wound and urinary
tract infections, and chronic invasive
procedures such as hemodialysis.
•Endocarditis complicates 6–25% of episodes
of catheter-associated Staphylococcus
aureus bacteremia; the higher rates are
detected by careful transesophageal
echocardiography (TEE) screening.
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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.

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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

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Injection drug use–associated endocarditis, especially that involving
the tricuspid valve, is commonly caused by S. aureus, which in many
cases is resistant to methicillin. Left-sided valve infections in addicts
have a more varied etiology. In addition to the usual causes of endocarditis,
these cases can be due to Pseudomonas aeruginosa and Candida
species, and sporadic cases can be caused by unusual organisms such
as Bacillus, Lactobacillus, and Corynebacterium species. Polymicrobial
endocarditis occurs among injection drug users. HIV infection in drug
users does not significantly influence the causes of endocarditis.

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From 5% to 15% of patients with endocarditis have negative blood
cultures; 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
bacteria (now designated Granulicatella and Abiotrophia species),
HACEK organisms, Coxiella burnetii, and Bartonella species. 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.

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Organisms that cause endocarditis 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. The organisms that commonly
cause endocarditis have surface adhesin molecules, collectively called
microbial surface components recognizing adhesin matrix molecules
(MSCRAMMs), that mediate adherence to NBTE sites or injured
endothelium. Adherence is facilitated by fibronectin-binding proteins
present on many gram-positive bacteria

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; by clumping factor
(a fibrinogen- and fibrin-binding surface protein) on S. aureus; by
fibrinogen-binding surface proteins (Fss2), collagen-binding surface
protein (Ace), and Ebp pili (the latter mediating platelet adherence)
in Enterococcus faecalis; and by glucans or FimA (a member of the
family of oral mucosal adhesins) on streptococci. Fibronectin-binding
proteins are required for S. aureus invasion of intact endothelium; thus
these surface proteins may facilitate infection of previously normal
valves. If resistant to the bactericidal activity of serum and the microbicidal
peptides released locally by platelets, adherent organisms proliferate
to form dense microcolonies.

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The causative microorganism is primarily
responsible for the temporal course of endocarditis. β-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 coagulasenegative
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, T. whipplei, or C. burnetii is exceptionally indolent.

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 Causative organism %
Streptococcus 30-40
Enterococcus Spp 5-10
Other streptococcus 10-25
S.Aureus 10-27
Coagulase –Ve staphylococcus 1-3
Gram –Ve bacilli 2-13
Fungi 2-5
Culture negative 5
HACEK 3

• Recently in developed countries S. aureus accounts for higher

proportions of IE than do the viridans, 32% Vs 18%.

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 Risk factors
Number of factors predispose to development of IE
IDU
Prosthetic valve
< 2month post-op nosocomial
2-12 month post-op nosocomial with delayed onset
>12 month community acquired
Nosocomial and health care associated endocarditis
Accounts for 10% of IE
Complication of bacteremia induced by procedures or
vascular device
Structural heart disease: -¾th of patients with IE have pre-existing structural cardiac abnormality.
Hx. Of endocarditis- recurrence is 4-5%
HIV infection- associated with unusual organisms like salmonella & listeria

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1- High Risk:
Prosthetic Heart Valves.
Previous Endocarditis.
Congenital cyanotic heart disease.
MR.
AR.
VSD.
PDA.
Coarctation of the Aorta.

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2- Intermediate Risk:
MVP with mild MR.
Pure MS.
TVD.
PVD.
HOCM (IHSS).
AS.
Non-Valvular prosthetic cardiac implants.
Intracardiac catheters.

3- Low Risk:
ASD ( Ostium secundum Type).
MVP without MR.

4- Other Risk Factors:

- IV. Drug abuse.
- AV shunts for hemodialysis.
- Massive Wounds such as burns.

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 Causative organisms:
1- ABE:
- Staph. aureus. - Hemophilus Influenza.
- Strep. Pneumonia. - enterococcal Species.
2- SBE:
- Strep. Viridans. - Strep. Bovis.
- Enterococcal Species. - HACEK group.
3- EPVE:Prosthetic valve endocarditis arising within 2 months of
valve surgery is generally the result of intraoperative
contamination of the prosthesis or a bacteremic postoperative
complication.
- Staph. Epidermedis. - Staph. Aureus.
- Asperigillus Species. - Gram -ve. Rods (E-Coli,
Pseudomonas).

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4- LPVE: prosthetic valve endocarditis within 2–12
months after surgery often represents delayed-onset
nosocomial infection
- St. Viridans. - Enterococci (S. Bovis &
Fecalis).
- CoNS
At least 85% of CoNS strains that cause prosthetic valve
endocarditis within 12 months of surgery are methicillin-
resistant; the rate of methicillin resistance decreases to
25% among CoNS strains causing prosthetic valve
endocarditis that presents >1 year after valve surgery.
5- Drug Abusers:
- Staph. Aureus. - Candidiasis.
- Pseudomonas & E-coli. - Enterococci.
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 Pathogenesis
Unless injured normal endothelium is resistant to infection by most
bacteria except S. aureus.
Endothelial injury at high velocity jet or low pressure side of
cardiac structural lesion causes aberrant flow direct
infection

un infected fibrin platelet thrombus called NBTE

serves as a site for bacterial attachment during transient bacteremia

NBTE can also arise due to hypercoagulable state(marantic
endocarditis)
If resistant to bactericidal activity of serum proliferate and
induce procoagulant state by eliciting tissue factor from monocytes
fibrin deposition platelet aggregation
infected vegetation
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CLINICAL PICTURE:
Can be acute or subacute
No
. absolute relationship b/n MO & temporal course of
endocarditis
Sn/Sx often begins as flue like illness with fever, chills, body
aches, sweats, arthalgia and myalgia
• Fever (80-90%): → Low grade in SBE.
→ High grade in ABE.
• Pallor: → Anemia (70-90%)
•chills, rigors and sweating (40-75%)
• Malaise and anorexia, wt loss (25-40%)
• New murmurs or increasing the grade of an old
murmurs (10-40%)
• Murmurs may be absent in severe cases.
• Delerium and headache.
•Chest pain, dyspnea, cough and hemoptysis.
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In patients with subacute presentations, fever is typically lowgrade
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 in patients who are elderly, are severely debilitated, or
have renal failure.

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Congestive heart failure (CHF) develops in 30–40% of patients as a
consequence of valvular dysfunction. Occasionally, CHF 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. 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.

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Abscesses may burrow from the aortic valve annulus
through the epicardium, causing pericarditis, or into the upper
ventricular septum, where they may interrupt the conduction system,
leading to varying degrees of heart block. Mitral perivalvular abscesses,
which are usually more distant from the conduction system, only
rarely cause conduction abnormalities; if such abnormalities occur in
this setting, the conduction pathway is most likely disrupted 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.

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The classic nonsuppurative peripheral manifestations of subacute
endocarditis (e.g., Janeway lesions; are related to prolonged infection;
with early diagnosis and treatment, these 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 occurs most often in the skin,
spleen, kidneys, skeletal system, and meninges. Arterial emboli, one half
of which precede the diagnosis, are clinically apparent in up to 50% of
patients

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Cerebrovascular emboli presenting as strokes or occasionally as
encephalopathy complicate 15–35% of cases of endocarditis. Again, 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. Emboli occurring late
during or after effective therapy do not in themselves constitute evidence
of failed antimicrobial treatment.

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Other neurologic complications include aseptic or purulent menin gitis, intracranial
hemorrhage due to hemorrhagic infarcts or ruptured mycotic aneurysms, and
seizures. (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.

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Almost 50% of endocarditis
associated with injection drug use is limited to the tricuspid
valve and presents with fever but with faint or no murmur and no
peripheral manifestations. Septic pulmonary emboli, which are common
with tricuspid endocarditis, cause cough, pleuritic chest pain,
nodular pulmonary infiltrates, or occasionally pyopneumothorax.
Infection of the aortic or mitral valves presents with the typical clinical
features of endocarditis, including peripheral manifestations

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Skin/mucosal lesion
petechiae-most common and non specific(10-40%)
 Splinter He
Janeway lesion
Osler’s node
Roth spot
Splenomegaly (15-50%)
Clubbing (10-20%)
Embolic events with infarction-extremities, spleen, kidney, bowel
(arterial emboli)-20-50%
Focal neurological signs ( embolic phenomena or meningitis ).-20-
40%
Aseptic/purulent meningitis
CHF
Seizure
Lab. findings -leukocytosis(20-30%)
• anemia (70-90%)
• microscopic hematuria(30-50%)
• Increased ESR >90%
• circulating immune complexes (65-100%)
• Rheumatoid factor -50%
• Elevated c- reactive protien level >90% 38
Diagnosis:-

is straight forward in patients with classic manifestations( bacteremia

or fungemia, active valvulitis, peripheral emboli, immunologic
vascular phenomena)
practical case definitions are important since under or over diagnosis
may harm the pt.
It is based on Duke’s diagnostic criteria.
The Duke criteria, stratified patients with suspected
IE into 3 categories:

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Definition of Infective Endocarditis According to the
Modified Duke Criteria
Definite infective endocarditis
• Pathological criteria
• Microorganisms demonstrated by culture or histological examination of
a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or
• Pathological lesions; vegetation or intracardiac abscess confirmed by
histological examination showing active endocarditis
• Clinical criteria
• 2 major criteria; or
• 1 major criterion and 3 minor criteria; or
• 5 minor criteria

Possible IE
• 1 major criterion and 1 minor criterion; or
• 3 minor criteria
Rejected
• Firm alternative diagnosis explaining evidence of IE; or
• Resolution of IE syndrome with antibiotic therapy for _4 days; or
• No pathological evidence of IE at surgery or autopsy, with antibiotic
• therapy for _4 days; or
• Does not meet criteria for possible IE as above

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 Definition of Terms Used in the Modified Duke
Criteria for the Diagnosis of IE
Major criteria
1. Blood culture positive for IE
• Typical microorganisms consistent with IE from 2
separate blood cultures: Viridans streptococci,
Streptococcus bovis, HACEK group, Staphylococcus
aureus; or community-acquired enterococci in the
absence of a primary focus; or
• Microorganisms consistent with IE from persistently
positive blood cultures defined as follows:
– At least 2 positive cultures of blood samples drawn 12 h
apart; or
– All of 3 or a majority of 4 separate cultures of blood (with
first and last sample drawn at least 1 h apart)
• Single positive blood culture for Coxiella burnetii or
anti–phase 1 IgG antibody titer >1:800 41
 Major criteria…
2. Evidence of endocardial involvement
• Echocardiogram positive for IE (TEE recommended for
patients with prosthetic valves, rated at least “possible
IE” by clinical criteria, or complicated IE paravalvular
abscess; TTE as first test in other patients) defined as
follows:
 oscillating intracardiac mass on valve or supporting
structures, in the path of regurgitant jets, or on implanted
material in the absence of an alternative anatomic
explanation
 abscess
 new partial dehiscence of prosthetic valve
 new valvular regurgitation (worsening or changing or
preexisting murmur not sufficient) 42
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.
To fulfill a major criterion, the isolation of an organism that causes
both endocarditis and bacteremia in the absence of endocarditis
(e.g., S. aureus, enterococci) must take place repeatedly (i.e.,
persistent
bacteremia) and in the absence of a primary focus of infection.
Organisms that rarely cause endocarditis but commonly contaminate
blood cultures (e.g., diphtheroids, CoNS) must be isolated repeatedly
if their isolation is to serve as a major criterion

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Minor criteria
• Predisposition, predisposing heart condition, or IDU
• Fever, temperature 38°C
• Vascular phenomena, major arterial emboli, septic
pulmonary infarcts, mycotic aneurysm, intracranial
hemorrhage, conjunctival hemorrhages, and Janeway’s
lesions
• Immunologic phenomena: glomerulonephritis, Osler’s
nodes, Roth’s spots, and rheumatoid factor
• Microbiological evidence: positive blood culture but
does not meet a major criterion as noted above or
serological evidence of active infection with organism
consistent with IE
• Echocardiographic minor criteria eliminated
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• 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.
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culture sets, separated from one another by at least 2 h, should be
obtained from different venipuncture sites over 24 h. 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,
especially those who have received antibiotics within the preceding
2 weeks. Thus, 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 receive empirical treatment
immediately after three sets of blood cultures are obtained over several
hours.

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Serologic tests can be used to implicate
organisms that are difficult to recover by blood culture: Brucella,
Bartonella, Legionella, Chlamydia 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 polymerase chain reaction to recover unique microbial DNA
or DNA encoding the 16S or 28S ribosomal unit (16S rRNA or 28S
rRNA); sequencing of these DNAs allows identification of bacteria
and fungi, respectively.

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Transthoracic echocardiography
(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.
TTE detects vegetations in 65–80% of patients with definite clinical
endocarditis but is not optimal for evaluating prosthetic valves or
detecting intracardiac complications. TEE is safe and detects vegetations
in >90% of patients with definite endocarditis; nevertheless, initial
studies may yield false-negative results in 6–18% of endocarditis
patients.

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When endocarditis is likely, a negative TEE result does not
exclude the diagnosis but rather warrants repetition of the study once
or twice in 7–10 days. TEE is the optimal method for the diagnosis
of PVE, the detection of myocardial abscess, valve perforation, or
intracardiac fistulae and for the detection of vegetations in patients
with CIED. In patients with CIED and negative blood cultures, a
mass adherent to the lead is likely to be a bland thrombosis rather
than an infected vegetation.

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ECHOCARDIOGRAPHY
Is central for diagnosis and management
Allows anatomic confirmation, size and detect intracardiac complications
Two types
TTE – non invasive
 for low initial patient risk and low clinical suspicion
detects only 65% of vegetations
can’t detect vegetations <2cm in diameter
TEE- invasive
•for high initial pateint risk
•moderate-high clinical suspicion of complication
•difficult imaging candidate
•detects in>90% of patients

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 COMPLICATIONS

CARDIAC
CHF common cause of death and indication for surgery
usaul cause is valvular insufficiency
more frequent in aorticvalve infection(29%) than Mitral valve(20%)or tricuspide(8%)
may develop acutely from perforation of native or bioprosthetic valve,rupture of infected
mitral chordae or valve obstruction
may develop insidiously despite therapy due to progressive worsenening of valvular
insuficiency and ventricular dysfunction
Rx is surgical:- valve replacement
• vegetectomy
• valvulectomy
Paravalvular absces
 reported in 30-40% at autopsy
 aortic valve and adjacent ring is more susceptable
 risk factors- IDU
-vegetation size??
 can extend to cardiac conduction tissue leading to various forms of heart block
 suspected when fever persists despite apropriate therapy or conduction abnormality occure
pericardditis, fistula- are rare
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Neurologic
second most common complication(25-35%)
can be presenting symptom
can be acute encephalopathy,
meningoencephalitis,purulent/aseptic meningitis, embolic stroke or
cerebral hemorrhage
stroke is common in mitral valve involvement
controversial for surgical indication; no difference seen in mortality
and neurologic deterioration b/n medical and surgical Rx
Embolization
occures in 22-25%
involve majore arterial beds including lungs, coronary arteries, spleen,
bowel and extremities.
~65%of embolic events involve CNS, and >90%occure at MCA.
common in aortic and mitral valve infection with
S.aureus,candida,HACEK,and Abiotrophia organisms
Can occur before diagnosis, during therapy or therapy is completed.
Most ocur in the first 2-4 weeks of therapy
Size of vegitation is controversial(>1cm) 52
The middle cerebral artery and its branches are involved most commonly.Three
percent of the cerebral emboli from all causes are secondary to IE. Cerebral
infarction, arteritis, abscesses, mycotic aneurysms, intracerebral or subarachnoid
hemorrhage, encephalomalacia, cerebritis, and meningitis have been reported.
Hemorrhagic transformation of an ischemic infarct due to septic emboli is the most
common mechanism leading to fatal intracerebral hemorrhage during IE.204 True
acute purulent meningitis is rare except in pneumococcal endocarditis, but
multiple microabscesses (cerebritis) due to S. aureus are relatively common in
acute staphylococcal IE

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Splenic absces
rare complication.
persistent/ recurent bacteremia, persistent fever, other signs of sepsis suggest
splenic absces.
abdominal CT/MRI best diagnostic tool.
Rx splenectomy
percutaneous drainage
splenectomy should be done before valve replacement
Mycotic aneurysm
uncommon complication
due to septic embolisation of vegetations.
common in intracranial arteries folowed by visceral and arrteries of upper
and lower extremities.
Pts may develop sever headache, alterd sensorium, or focal neurologic
deficit.
ECMA- often asymptomatic.

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They are more common with viridans streptococcal infections and are found in
10% to 15% of autopsied cases. They may arise by any of several mechanisms: (1)
direct bacterial invasion of the arterial wall with subsequent abscess formation or
rupture, (2) septic or bland embolic occlusion of the vasa vasorum, or (3) immune
complex deposition with resultant injury to the arterial wall. The aneurysms tend
to occur at bifurcation points. They are found most commonly in the cerebral
vessels (primarily the peripheral branches of the middle cerebral artery), but they
also occur in the abdominal aorta; the sinus of Valsalva; a ligated patent ductus
arteriosus; and the splenic, coronary, pulmonary, and superior mesenteric arteries.
Mycotic aneurysms usually are clinically silent until rupture occurs; consequently,
their true incidence in active IE is unknown.

55
 ANTICOAGULATION
Controversial particularly in prosthetic valve endocarditis.

Native valve IE
use of prophylactic anticoagulation is not justified in this group and there is no
evidence that it decreases incidence of embolization.
In contrast prompt use of antibiotics reduces incidence of embolization.
Prosthetic valve IE
discontinuation-hemorrhagic transformation
continuation- aggravate thrombus formation
antibiotic treatment is more important than anticoagulation.
USE OF ASPRINE
Rate of embolic stroke was not significantly different with
aspirin compared to placebo and there is high incidence of
bleeding in patients taking aspirin.
Routine use of aspirin for established IE is not recommended.

56
 TREATMENT
Antimicrobial
difficult to eradicate micro organism because site is relatively in accessible to
host defense and bacteria is non growing and metabolically in active.
since all bacteria should be killed therapy need to be bactericidal and for
prolonged period.
Initiation of therapy should balance need for surgery and establish
microbiologic Dx.

57
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

58
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.

59
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

60
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 (Table 155-4). 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

61
. 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

62
. 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

63
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.

64
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
(Table 155-4). 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

65
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.

66
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).

67
68
• 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

69
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

70
 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

71
CIED Endocarditis Removal of all hardware is recommended for
patients with established CIED infection (pocket or intracardiac lead)
or erosion of the device through the skin. Percutaneous lead extraction
is preferred. With lead vegetations of >3 cm and the resulting
risk of a pulmonary embolus or with retained hardware after
attempted percutaneous extraction, surgical removal should be
considered. Removal of the infected CIED during the initial hospitalization
is associated with increased 30-day and 1-year survival rates over those
attained with antibiotic therapy and device retention. If
necessary, the CIED can be reimplanted percutaneously or surgically
(epicardial leads) at a new site after at least 10–14 days of effective
antimicrobial therapy. CIEDs should be removed and replaced
subsequently when patients undergo valve surgery for endocarditis.

72
73
 MONITORING THERAPY
Clinical –fever subside with in 7 days ,if persists abscess.
Laboratory
serum concentration of amino glycosides
and vancomicine.
toxicity occur in 25-40%, during third week
of therapy.
blood culture -daily until sterile
-negative within two days
- S. aureus 3-5 days.
ESR, rheumatoid factor resolve slowly and don’t
reflect response to treatment.
Vegetation become smaller with effective therapy
at 3 month -½ unchanged
- ¼ slightly larger

74
 Culture-Negative Endocarditis
• Positive blood cultures are a major diagnostic criterion for IE
and key to identifying the etiologic agent and the optimal
antimicrobial regimen.
• Blood cultures are negative in up to 20% of patients with IE
diagnosed by strict diagnostic criteria.
• Failure to culture the microorganism causing endocarditis
may result from: -
• inadequate microbiological techniques
• infection with highly fastidious bacteria
• nonbacterial pathogens
• previous administration of antimicrobial agents before blood cultures were
obtained.
• Administration of antimicrobial agents to IE patients before
blood cultures are obtained reduces the recovery rate of
bacteria by 35% to 40%.
• Selection of the most appropriate medical therapy for patients
with culture-negative endocarditis is difficult.
75
Emperic Antibiotic Therapy for culture negative Endocarditis
There is a need to provide empiric antimicrobials for all likely
pathogens.
• Selection of an empirical treatment regimen should include
consideration of epidemiological features and the clinical
course of infection.
• Patients should be classified into 1 of 2 groups when choice of
empirical therapy is considered.
Group-I includes patients who received antibiotic therapy before
collection of blood cultures.
For those with acute clinical presentations of native valve
infection-- coverage for S aureus should be provided.
For patients with a subacute presentation, coverage of S
aureus, viridans group streptococci, and enterococci should be
given.
Patients with culture-negative prosthetic valve infection should
receive vancomycin if onset of symptoms begins within 1 year of
prosthetic valve placement to provide coverage of oxacillin-
resistant staphylococci. 76
• Coverage for aerobic Gram-negative bacilli with
cefepime 2 g IV every 8 hours could be considered for
onset of infection within 2 months of valve
replacement. If symptom onset is 1 year after valve
placement, then infection is more likely to be
cloxacillin-susceptible staphylococci, viridans group
streptococci, and enterococci, and antibiotic therapy
for these potential pathogens should be administered
for at least 6 weeks.
The second group of patients has infection caused by
uncommon or rare endocarditis pathogens that do not grow
in routinely used blood culture systems.
These are Bartonella species, Chlamydia species, Coxiella
burnetii, Brucella species, Legionella species, Tropheryma
whippleii, and non-Candida fungi.
• Antibiotic regimens should include at least 2 weeks of
aminoglycoside therapy.
77
78
Noninfectious causes of valvular vegetations can
produce a syndrome similar to culture-negative
endocarditis.
Antiphospholipid syndrome,
Autoimmune disorders, particularly SLE,
and
Malignancies

79
 OUT COME
poor out come: –
• old age
• sever comorbid condition
• delayed diagnosis
• prosthetic valve
• invasive( S. aureus) or resistant (P. aeroginosa) pathogen
• Intracardiac complication
• Major neurologic complication
• Overall survival rates
• for patients with native valve endocarditis caused by viridans streptococci,
HACEK organisms, or enterococci (susceptible to synergistic therapy) are 85–
90%.
• For S. aureus native valve endocarditis in patients who do not inject drugs,
survival rates are 55–70%, whereas 85–90% of injection drug users survive this
infection.
• Prosthetic valve endocarditis beginning within 2 months of valve replacement
results in mortality rates of 40–50%, whereas rates are only 10–20% in later-
onset cases.

80
• Prosthetic valve endocarditis (PVE) can arise early or late after
surgery. The timing of the infection reflects different pathogenic
mechanisms that, in turn, influence the epidemiology, microbiology,
pathology, and clinical manifestations of the infection.
• Early infection  — Microorganisms can reach the valve prosthesis by
direct contamination intraoperatively or via hematogenous spread
during the initial days and weeks after surgery. These pathogens have
direct access to the prosthesis-annulus interface and to perivalvular
tissue along suture pathways because the valve sewing ring, cardiac
annulus, and anchoring sutures are not endothelialized early after
valve implantation. These structures are coated with host proteins,
such as fibronectin and fibrinogen, to which some organisms can
adhere and initiate infection

81
• Late infection  — As the sewing ring, sutures, and adjacent tissues
become endothelialized over the months after valve replacement,
sites for adherence of microorganisms and access to host tissues
adjacent to the prosthesis are altered. The pathogenesis of late PVE
has been postulated to resemble native valve endocarditis (NVE)

82
• Unless the infecting organism is Staphylococcus aureus or another
highly virulent or invasive pathogen, the perivalvular tissues are less
likely to be affected in late PVE since endothelialization limits access
to these tissues. Later onset infections tend to be less invasive, are
less often complicated by perivalvular abscess formation and valve
dehiscence, and are more commonly restricted to the sewing ring or
the bioprosthetic leaflet.
• However, the leaflets of porcine bioprosthetic valves experience age-
related alterations in their surface characteristics. These aging leaflets
become sites for platelet-fibrin thrombus deposition and subsequent
infection. As a result, the infection rates on bioprostheses increase
during this later period when compared to mechanical valves 

83
• The risk is greatest during the initial three months after surgery,
remains high through the sixth month, and then falls gradually with
an annual rate of approximately 0.4 percent from 12 months
postoperatively onward for the life of the valve recipient . The
percentage of patients developing PVE during the initial year after
valve replacement ranges from 1 to 3 percent in studies with active
follow-up; by five years, the cumulative percentage ranges from 3 to
6 percent 

84
• Although conclusions vary among studies, infection generally occurs
with equal frequency at aortic and mitral sites and on mechanical
and bioprosthetic devices during the first postoperative year . As
noted above, bioprosthetic valves carry a greater risk for infection
than mechanical valves after the first 18 months . When a valve is
replaced in a patient with endocarditis, whether the infection was
active or healed at the time of surgery, there is an increased risk for
both early (some of which is recrudescence of active endocarditis)
and late PVE

85
• Healthcare-associated infection  — Some cases of prosthetic valve
endocarditis result from infection acquired in healthcare settings,
both inpatient (nosocomial) and outpatient (non-nosocomial)
• 70 percent were labeled as nosocomial and 30 percent as outpatient
acquired. Approximately 70 percent of the healthcare-associated
infections were diagnosed within the first year after valve
implantation, with the majority occurring within the first sixty days.
Staphylococcus aureus was the most common organism, being
identified as the pathogen in 34 percent of cases.
• Nosocomial bacteremia occurring in patients with prosthetic valves
carries a significant risk for seeding the prosthesis

86
definition

• Intravenous therapy, wound care, or specialized nursing care at

home, or intravenous chemotherapy within the prior 30 days
• Residence in a nursing home or other long-term care facility
• Hospitalization in an acute care hospital for two or more days within
the prior 90 days
• Attendance at a hospital or hemodialysis clinic within the prior 30
days

87
• The most frequently encountered pathogens in early PVE (within two
months of implantation) were Staphylococcus aureus and coagulase-
negative staphylococci; next in frequency were gram-negative bacilli
and fungal infection.
• The most frequently encountered pathogens in late PVE (two months
after valve implantation) were streptococci and S. aureus, followed
by coagulase negative staphylococci and enterococci. Culture-
negative cases occur in all time intervals after valve surgery; they are
due largely to the confounding effect of recent or concurrent
antibiotic therapy. Coxiella burnetii, although an unusual cause of
endocarditis, has a unique predisposition to cause PVE. Thus, in areas
where this pathogen is endemic, it must be considered a potential
cause of late onset culture-negative PVE.

88
• Cases occurring during the initial two months after surgery are often
nosocomial in origin, which accounts for the spectrum of causative
organisms. In contrast, those cases presenting more than 12 months
after valve surgery are usually caused by the same pathogens that
produce native valve endocarditis (NVE) in patients who are not
injection drug users, since late PVE, like NVE, usually results from
transient bacteremia occurring among ambulatory patients 
• Cases that present after 2 months and before 12 months post-surgery
are a blend of delayed onset nosocomial and community-acquired
infections; this is reflected in the spectrum of organisms encountered
in these cases.

89
• The coagulase-negative staphylococci causing PVE during the initial
year after surgery are almost exclusively S. epidermidis. Between 84
and 87 percent of these organisms are methicillin-resistant and thus
resistant to all of the beta-lactam antibiotics , with the likely
exception of ceftaroline
• By contrast, almost half of the coagulase-negative staphylococci
causing PVE one year or more after surgery are non-epidermidis
species, and only 22 to 30 percent are methicillin-resistant

90
• Methicillin-resistant coagulase-negative staphylococci, while
uniformly possessing the resistant genotype, do not always express
the phenotype, a phenomenon called heteroresistance. This makes
detection of methicillin-resistance among coagulase-negative
staphylococci more difficult. As a result, before embarking upon
therapy with a beta-lactam antibiotic, the microbiology laboratory
must be asked to thoroughly exclude possible methicillin-resistance.
If this cannot be done, methicillin resistance should be assumed. 

91
• The histologic features that characterize PVE in bioprosthetic valves
are not well defined. As bioprosthetic valves degenerate, they may
form noninfective, calcific, vegetative-like lesions and inflammatory
infiltrates thus potentially causing a noninfectious process to be
misdiagnosed as PVE
•  Histologically, PVE was characterized by microorganisms,
vegetations, and neutrophil-rich, inflammatory infiltrates. In contrast,
inflammatory infiltrates in valve tissue samples from the noninfective
control group consisted mainly of macrophages and lymphocytes. A
neutrophil surface area with a cutoff value of >1.5 percent of total
valve tissue surface was highly specific for PVE (94 percent)

92
• Valvular dysfunction, fever which persists for nine days or more
despite appropriate antibiotic therapy, new electrocardiographic
conduction disturbances, and echocardiographic evidence of abscess
formation are clinical manifestations of invasive infection
• DIAGNOSIS  — Laboratory findings in patients with prosthetic valve
endocarditis (PVE) are similar to those noted in patients with native
valve endocarditis (NVE) of comparable duration.

93
• Blood cultures  — In the absence of prior antibiotic therapy, blood
cultures will be positive in 90 percent or more of patients with PVE.
Because bacteremia is continuous, cultures will be positive regardless
of whether or not blood cultures are obtained in proximity to the
fever. When blood cultures are drawn over a period of hours to days
in a patient with a prosthetic valve and all or most are positive, PVE is
highly probable. The duration of documented bacteremia is
particularly important when the isolate is a common contaminant,
such as coagulase-negative staphylococci or diphtheroids. A high rate
of blood culture positivity, or molecular evidence that a sporadically
isolated organism represents a single clone, helps to distinguish
infecting pathogens from contaminants

94
• If antibiotics have not been administered prior to obtaining blood
cultures, it is unusual to have persistently negative blood cultures in
patients with clinically overt PVE. Nevertheless, culture-negative
cases can occur when infection is caused by fastidious organisms
such as Legionella species, Bartonella species, Coxiella burnetii,
Mycoplasma hominis, fungi other than Candida species, and the
HACEK organisms.

95
•  Although transthoracic (TTE) and transesophageal echocardiograms
are complementary in the diagnosis of PVE, TEE has a sensitivity of 82
to 96 percent compared with 17 to 36 percent for TTE . This
increased sensitivity is achieved without regard to valve position and
without loss of specificity

96
• A high resolution biplane or multiplane transducer that allows
continuous-wave and pulse-wave Doppler and color-flow imaging
should be employed. TTE provides superior images of the ventricular
surfaces of prostheses in the mitral, tricuspid, and aortic positions,
whereas the atrial surfaces of the mitral and tricuspid valves and the
aortic surface and outflow track of prostheses in the aortic position
are better viewed by TEE. TEE is unquestionably superior to TTE for
visualizing a mitral valve prosthesis.

97
• TEE is also superior to TTE in the detection of abscesses, fistulae, and
paraprosthetic leaks 
• The negative predictive value of a full echocardiographic evaluation
of a patient with suspected PVE is 86 to 94 percent. Nevertheless, if
PVE is strongly suspected in the face of a negative evaluation, repeat
echocardiography one week later can provide evidence of PVE in
some cases

98
• There was no diagnostic benefit beyond the third TEE. Although
echocardiography has replaced other modalities of cardiac imaging in
the diagnosis of PVE, including cardiac catheterization (which is now
reserved for defining coronary artery anatomy), multislice computed
tomography may be comparable to TEE, and in some instances of
PVE, may yield diagnostic evidence of infection where TEE has been
non-diagnostic

99
• When sporadic blood cultures yield coagulase-negative staphylococci
or when only several cultures have been obtained and are positive
for these organisms, molecular techniques, such as DNA examination
by pulsed-field gel electrophoresis, should be used to compare the
isolates. Establishing clonality of isolates from separate cultures
argues against contamination and favors that the isolates are true
pathogens . However, there is a potential for polyclonal infections to
arise, especially from direct contamination in the operating room.

100
Pelletier and Petersdorf criteria  — The classification scheme of Pelletier and
Petersdorf consisted of three case categories: definite, probable, and possible.
•Definite IE required histologic evidence of infected endocardial vegetation(s)
from examination of tissue obtained from cardiac surgery, embolectomy, or
autopsy.
•Probable IE required either uniformly positive blood cultures with known
underlying valvular heart disease and evidence of emboli to the skin or
viscera; or negative blood cultures in individuals with fever (>38ºC), new
regurgitant valvular heart murmurs, and embolic phenomena.
•Possible IE required either uniformly positive blood cultures with known
underlying heart disease or embolic phenomena; or negative blood cultures
with fever, known underlying valvular heart disease, and embolic episodes
These criteria were reasonably specific but lacked sensitivity. In practice, many
patients with clinical features presumed to be due to IE did not meet the
above criteria.

101
• von Reyn criteria  — In 1981, von Reyn and colleagues modified the case
definitions of Pelletier and Petersdorf with the intent of improving specificity and
clinical utility. These authors divided cases into four categories: definite,
probable, possible, and rejecte.
• As with the previous classification system, pathological confirmation of
vegetations or an abscess was required to define a case as definite. Other criteria
for diagnosis included:
• Persistent bacteremia
• Evidence of active endocardial pathology (eg, the presence of a new regurgitant
murmur)
• Predisposing valvular heart disease
• The presence of vascular phenomena such as emboli or splinter hemorrhages
• The von Reyn criteria lacked prospective validation, although they improved the
specificity of the classification system of Pelletier and Petersdorf. Furthermore,
application of the von Reyn criteria results in a large proportion of cases being
classified as probable or possible, because most patients with IE do not require
valve surgery during the acute phase of their illness 

102
• DUKE CRITERIA  — In 1994, investigators from Duke University
modified the von Reyn criteria to include the role of
echocardiography in diagnosis. They also expanded the category of
predisposing heart conditions to include injection drug use . Later,
Fournier et al proposed further expansion of the Duke criteria to
include serologic criteria for a diagnosis of Q fever endocarditis . In
2000, Li et al modified the original Duke criteria to include Q fever
serology as a major criterion and refined the criteria to define a case
as probable IE

103
Definite endocarditis  — According to the Duke criteria, endocarditis is
considered definitely present if any one of the following pathological
findings or combinations of clinical findings are present :
•Direct evidence of endocarditis based upon histological findings (a
pathological criterion)
•Positive Gram stain results or cultures of specimens obtained from
surgery or autopsy (a pathological criterion)
•Two major clinical criteria
•One major and any three minor clinical criteria, or
•Five minor clinical criteria

104
• All were correctly classified if a single positive blood culture for
Coxiella burnetii and an antiphase I IgG antibody titer to C. burnetii
greater than 1:800 were changed from minor to major criteria.

105
• Possible endocarditis  — Possible endocarditis is defined as the
presence of one major and one or two minor clinical criteria or the
presence of three minor clinical criteria
• Rejected endocarditis  — The diagnosis of endocarditis is considered
rejected if any of the following are present:
• A firm alternate diagnosis is made
• Resolution of clinical manifestations occurs after four days of
antibiotic therapy or less
• No pathological evidence of infective endocarditis is found at surgery
or autopsy after antibiotic therapy for four days or less
• Clinical criteria for possible or definite infective endocarditis not met

106
• The negative predictive value of the Duke criteria for rejected
endocarditis was at least 92 percent in one report of 49 cases of
rejected IE cases . There were no proven cases of IE; one patient had
"possible" IE at autopsy.

107
108
• TEE had a positive predictive value of 90 percent for both native and
prosthetic valve endocarditis in this study. The negative predictive
value of TEE is nearly 100 percent for patients with native valves, but
patients with prosthetic valves may have a negative TEE and still have
IE. In the latter patients, clinical assessment is especially important.
TEE improved the sensitivity of the Duke criteria when clinical
evidence of IE was present, especially in patients with prosthetic
valves

109
• Cerebral imaging  — Routine magnetic resonance imaging (MRI) may
be useful in patients with definite or suspected IE. In one study
including 53 patients, early use of cerebral MRI led to the
reclassification from possible to definite IE in one-third of cases
• Prolonged staphylococcal bacteremia in patients with long-term
central vascular catheters is usually an indication for long-term
antistaphylococcal therapy even if Duke criteria for endocarditis are
not met 

110
The diagnosis is usually obvious when a patient has the characteristic
findings of IE:
•Several positive blood cultures in the presence of a well recognized
predisposing cardiac lesion
•Evidence of endocardial involvement
•However, some patients with IE do not have positive blood cultures
(ie, culture-negative endocarditis), and approximately one-third to
one-fourth of patients have no identifiable predisposing cardiac lesion
at disease onset. The presence of atypical features may result in
misdiagnosis or a correct diagnosis that is delayed

111
• HISTORY  — During the initial assessment of patients with suspected
endocarditis, 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, such as
indwelling intravascular catheters or intravenous drug use.
• With the rise in rates of infective endocarditis (IE) due to S. aureus in
the 21st century, IE is more often presents as acute rather than
chronic disease 

112
• A vigorous search should be undertaken for the classic clinical
stigmata of endocarditis, including evidence of small and large emboli
with special attention to the fundi, conjunctivae, skin, and digits. A
neurologic evaluation may reveal evidence of focal neurologic
impairment; it is also useful as a baseline examination should such
abnormalities appear later. 

113
• Associated peripheral cutaneous or mucocutaneous lesions of
infective endocarditis (IE) include petechiae, splinter hemorrhages,
Janeway lesions, Osler's nodes, and Roth spots. Petechiae are not
specific for IE but are its most common skin manifestation . They may
be present on the skin, usually on the extremities, or on mucous
membranes such as the palate or conjunctivae, the latter usually as
hemorrhages best seen with eversion of either upper or lower
eyelids. Splinter hemorrhages, also nonspecific for endocarditis, are
nonblanching, linear reddish-brown lesions found under the nail bed 

114
Janeway lesions, Osler's nodes, and Roth spots are more specific (but
still not diagnostic) for IE. All three findings are uncommon in modern
practice.
•Janeway lesions are macular, nonpainful, erythematous lesions on the
palms and soles .
•Osler's nodes are painful, violaceous nodules 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.

115
• A minimum of three blood cultures should be obtained over a time
period based upon the severity of the illness. If the tempo of illness is
subacute and the patient is not critically ill, it is reasonable and often
preferable to delay therapy for one to three days while awaiting the
results of blood cultures and other diagnostic tests. However, if the
patient is acutely ill, three blood cultures should be obtained over a
one-hour time span before beginning empiric therapy. Almost all
cases of bacterial infective endocarditis (IE) are due to aerobic
organisms; thus, culturing for anaerobes is rarely useful or necessary.

116
• The bacteriologic diagnosis of IE is facilitated by the relative
constancy, rather than random, release of bacteria from the cardiac
vegetations . However, since many patients with bacterial
endocarditis have low grade bacteremia (eg, 1 to 10 CFU/mL of
blood) , a minimum of 10 mL (and preferably 20 mL) of blood should
be obtained from adults and 0.5 to 5 mL from infants and children. In
one study, blood cultures inoculated with at least 5 mL of blood had a
significantly higher detection rate for bacteremia than bottles
inoculated with less than 5 mL of blood (92 versus 69 percent) . The
estimated yield of blood cultures in bacteremic adults increased
approximately 3 percent per mL of blood cultured

117
• Each set of cultures should be obtained from separate venipuncture
sites, and, when possible, blood cultures should not be obtained
from preexisting vascular catheters. 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

118
• Organism  — Not all microorganisms have the same propensity to
cause endocarditis. As an example, organisms such as viridans
streptococci and Staphylococcus aureus are more likely to cause
endocarditis than are gram-negative rods such as Escherichia coli and
Proteus spp. This distinction is important. The Duke Criteria for the
diagnosis of endocarditis define the following organisms as "typical
causes" of IE
• Staphylococcus aureus
• Viridans streptococci and Streptococcus bovis
• Enterococci
• HACEK group organisms

119
The probability of endocarditis varies by species of bacteria. As
examples:
•S. sanguis bacteremia is more often indicative of endocarditis than is
bacteremia due to S. milleri (also known as S. anginosus).
•Bacteremia with groups A or C streptococci are seldom associated
with IE whereas group G streptococcal infection is often indicative of
endocarditis
•In a study of enterococcal bacteremia cited above, infection with E.
faecalis, compared to other enterococcal species, was associated with
IE by both univariate and multivariate analysis

120
• Positive cultures  — The interpretation of positive blood cultures in
patients with suspected endocarditis is confounded by the fact that
false-positive results occasionally occur despite use of the most
exacting techniques for collection and processing. When organisms
such as Propionibacterium spp, Corynebacterium spp, Bacillus spp,
and coagulase-negative staphylococci are recovered from a single
blood culture or a minority of blood culture bottles, the result is
probably falsely positive. However, since all of these organisms are
capable of causing endocarditis, it is important to determine if the
bacteremia is persistent

121
The definition of persistent bacteremia varies with the likelihood that
the organism is a cause of endocarditis :
•For an organism likely to cause endocarditis (eg, S. aureus, viridans
streptococci), two positive samples collected more than 12 hours apart
•For an organism that is more commonly a skin contaminant, three or
a majority of four or more separate blood cultures are positive and the
first and last samples are collected at least one hour apart

122
The following findings may be identified among patients with IE but are
relatively nonspecific:
•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 elevated rheumatoid factor titer in patients without a known prior
rheumatologic disorder is one of six minor criteria in the Duke diagnostic
schem

123
•  TTE has relatively low sensitivity for vegetation in infective
endocarditis (IE) (29 to 63 percent in different series) although the
specificity approaches 100 percent . Thus, the absence of vegetation
does not preclude the diagnosis and, as described in the next section,
TEE is usually warranted. However, the finding of normal valves (both
morphology and function) substantially reduces the probability of IE.
In one study, 96 percent of patients with normal valves and no
vegetation on TTE also had a negative TEE

124
it is reasonable to begin with TEE in selected settings:
•Limited transthoracic windows (eg, due to obesity, chest wall
deformity, or mechanical ventilation)
•Prosthetic valves, especially prosthetic aortic or mitral valves in which
shadowing may make visualization difficult by TTE
•A prior valvular abnormality (including previous endocarditis)
•S. aureus bacteremia
•Bacteremia due to an organism known to be a common cause of IE
such as viridans streptococci

125
For patients with a normal TTE (both morphology and function), the
likelihood of IE is very low . A subsequent TEE is not necessary unless
one or more of the following is present:
•A high clinical suspicion of IE (persistently positive blood
cultures and/or multiple minor criteria for endocarditis)
•A technically limited TTE study

126
Some patients with abnormal on findings on TTE may require further
evaluation by TEE. These include patients with significant valvular
regurgitation in whom surgery is contemplated and patients who have
one or more of the following risk factors for perivalvular abscess:
•Conduction delay by ECG that is not known to be old
•Persistent fever despite appropriate antimicrobial therapy
•Aortic valve endocarditis

127
• Controversies  — There are a number of unresolved controversies
related to the use of echocardiography in the diagnosis and
management of patients with IE:
• Some experts recommend that all patients with suspected IE,
especially those with staphylococcal bacteremia should have a TEE as
the initial study [ 21 ]. However, we regard the steps outlined above
as sufficient to exclude IE without TEE in many cases, and do not
require that all patients undergo this invasive procedure.
• Some experts believe that patients with staphylococcal bacteremia
associated with a condition (such as vertebral osteomyelitis) that will
require a protracted course of antimicrobial therapy do not require
echocardiography to rule out associated IE, especially if there are no
hemodynamic signs or symptoms of IE. However, we recommend
that echocardiography be performed in such patients, since a positive
result will influence the type and intensity of follow-up examinations

128
• On theoretical grounds, some physicians delay echocardiography for
several days after the onset of bacteremia, because both TTE and TEE
can be falsely negative if vegetations are small (and, occasionally, if
previously present vegetations have embolized). In addition, even TEE
can miss a perivalvular abscess, especially if the study is done in the
first few days of illness 

129
Infection of a prosthetic heart valve can be difficult to diagnose and
manage. Optimal treatment of prosthetic valve endocarditis (PVE)
requires:
•Identification of the causative microorganism.
•Selection of a bactericidal antimicrobial regimen of proven efficacy.
•A clear understanding of the intracardiac pathology and attendant
complications of PVE.
•Surgical intervention, especially when infection has extended beyond
the valve to contiguous cardiac tissue.

130
• It is essential to isolate the causative organism in patients with
suspected PVE. For patients who are hemodynamically stable with an
indolent clinical course, antibiotic therapy should be delayed pending
the blood culture results. This delay allows additional blood cultures
to be obtained without the confounding effect of antibiotics, which is
particularly important for patients who have received recent
antimicrobial agents and whose initial blood cultures may be
negative.

131
132
• However, patients presenting with hemodynamic instability or acute
disease should receive empiric antibiotics promptly after three sets of
blood cultures have been obtained. Empiric antibiotic therapy with
three agents should be initiated: vancomycin , gentamicin , and
either cefepime or a carbapenem. Subsequent therapy should be
adjusted based on culture results;

133
• No randomized controlled studies have evaluated the optimal
duration of therapy for PVE. Treatment guidelines from the American
Heart Association (AHA) and the European Society for Cardiology
(ESC) recommend that PVE should be treated with an agent(s) that is
bactericidal for the isolated microorganism for at least six weeks

134
• Optimal therapy of PVE caused by methicillin-resistant S. aureus with
reduced vancomycin susceptibility or when failing vancomycin
therapy has not been established. High-dose daptomycin (if the
isolate remains daptomycin susceptible), telavancin , ceftaroline ,
and linezolid are often active against these organisms, although
clinical experience in the treatment of PVE is limited

135
• Optimal therapy of PVE caused by methicillin-resistant S. aureus with
reduced vancomycin susceptibility or when failing vancomycin
therapy has not been established. High-dose daptomycin (if the
isolate remains daptomycin susceptible), telavancin , ceftaroline ,
and linezolid are often active against these organisms, although
clinical experience in the treatment of PVE is limited
• Rifampin  —  Rifampin appears to have the unique ability to kill
staphylococci that are adherent to foreign material, based upon in
vitro data, evidence from animal model experiments, and clinical
observations . This drug is an essential component of regimens used
to treat staphylococcal PVE. However, bacterial cells have a relatively
high intrinsic mutation rate for the gene controlling the rifampin site
of action. These mutations allow the selection of a rifampin-resistant
subpopulation when large numbers of staphylococci are exposed to
ineffective rifampin-containing regimens 

136
• STREPTOCOCCI  — Combination therapy with a beta-lactam antibiotic
and an aminoglycoside (if the isolate does not exhibit high level
resistance to the aminoglycoside) is the preferred regimen for
streptococcal prosthetic valve endocarditis (PVE). In an effort to
provide maximal therapy, combination beta-lactam-aminoglycoside
therapy is used to achieve synergistic killing of the organism. This
synergistic interaction is similar to that seen with combination
therapy for enterococcal endocarditis

137
• If the streptococcus is relatively resistant to penicillin (MIC
>0.12 mcg/mL), the AHA recommends that the aminoglycoside
should be continued for the entire four to six weeks of therapy, if not
precluded by nephrotoxicity . Although there is a theoretical benefit
to a longer course of aminoglycoside therapy when treating PVE
caused by these less penicillin-susceptible strains, there are not
sufficient data upon which to base recommendations on duration of
therapy or dosing frequency.

138
• We would recommend gentamicin be administered in three divided
doses for two weeks when the isolate has penicillin MIC
>0.12 mcg/mL and for four to six weeks if the MIC >0.5 mcg/mL or if
PVE is caused by Abiotrophia defectiva, Granulicatella spp, or
Gemella spp. We base these recommendations on limited data
generated from native valve endocarditis treatment and the risk of
enhanced aminoglycoside nephrotoxicity with longer courses of
therapy. The ESC recommends that the aminoglycoside be given
during the initial two weeks of treatment even when the isolate is
relatively resistant to penicillin (MIC 0.125 to 2.0 mcg/mL) and for
three to four weeks if the MIC is >2.0 mcg/mL

139
• ENTEROCOCCI  — To achieve bactericidal activity against enterococci
requires the synergistic interaction of a cell wall active agent
(penicillin, ampicillin , or vancomycin ) and an aminoglycoside ( 
gentamicin orstreptomycin ) 
we, along with the AHA and ESC recommend combination therapy with
a cell wall active agent (penicillin, ampicillin , or vancomycin ) plus an
aminoglycoside (usually gentamicin or streptomycin ) for treatment
of PVE caused by enterococci (as long as the strain is confirmed to be
susceptible).

140
• Cephalosporins are not usually active against enterococci and also do
not interact with aminoglycosides to result in bactericidal synergy.
The cephalosporins should not be used alone as the cell wall active
agent in the treatment of enterococcal PVE in patients allergic to
penicillin. Rather, such patients should be treated with vancomycin 
plus an aminoglycoside. When the risk of nephrotoxicity with this
regimen is unacceptable, patients should be desensitized to penicillin
to allow treatment with penicillin or ampicillinplus an
aminoglycoside.

141
• If the enterococcus has high-level resistance to both streptomycin 
and gentamicin , synergy is not feasible and an aminoglycoside
should not be administered. When resistance precludes bactericidal
therapy, a prolonged course of 8 to 12 weeks of one of the cell wall
active agents should be administered instead, but therapy in patients
with native valve endocarditis has only a 40 percent chance of being
successful.
• Data in native valve E. faecalis endocarditis suggest that ampicillin (2
g every 4 hours) and ceftriaxone (2 g every 12 hours) for six weeks
may yield superior cure rates than single drug therapy . Surgery may
be indicated for patients not sufficiently responsive to therapy.

142
• Optimal therapy of PVE caused by vancomycin -resistant E. faecium
(VRE) organisms, which often are also resistant to penicillin and 
ampicillin , and highly resistant to gentamicin and streptomycin , has
not been established. VRE are occasionally susceptible to penicillin
and ampicillin and may not have high-level resistance to streptomycin
and gentamicin. A full evaluation of the isolates resistance profile is
required to select optimal therapy. Although quinupristin-
dalfopristin (E. faecium only) and linezolid (E. faecium and E. faecalis)
are often active against these organisms, their effectiveness in the
treatment of PVE caused by VRE is not known 

143
• HACEK  — Because some of these organisms are ampicillin -resistant
due to the production of beta-lactamase, and all are highly
susceptible to third generation cephalosporins, we, along with the
AHA recommend therapy for HACEK PVE with one of the following
antibiotics: ceftriaxone , cefotaxime , or a comparable third
generation cephalosporin; ampicillin-sulbactam ;
or ciprofloxacin (recommended only for patients unable to tolerate
cephalosporin or ampicillin therapy), administered for six weeks . The
ESC recommends ampicillin (if the organism is susceptible) or a third
generation cephalosporin. Patients with HACEK PVE, who do not have
valvular dysfunction, generally can be cured with antibiotics alone

144
• CORYNEBACTERIA (DIPHTHEROIDS)  — If the strain is susceptible
to gentamicin (MIC <4.0mcg/mL), penicillin plus gentamicin will
result in synergistic bactericidal activity and is recommended as
therapy. Gentamicin resistance precludes bactericidal
synergy . Vancomycin is bactericidal against diphtheroids and is
recommended for therapy when strains are resistant to gentamicin or
when patients are allergic to penicillin.

145
• GRAM-NEGATIVE BACILLI  — We recommend treatment of PVE
caused by gram-negative bacilli be based upon the susceptibility of
the causative organism. Where possible, a synergistic bactericidal
regimen should be used. Treatment for Pseudomonas aeruginosa is
based upon experience in patients with NVE. If the organism is
susceptible, high dose tobramycin (8 mg/kg per day IV or
intramuscularly in once-daily doses with maintenance of peak and
trough concentrations of 15 to 20 mcg/mL and less than or equal to
2 mcg/mL, respectively) plus ticarcillin, piperacillin , cefepime ,
or ceftazidime is recommended

146
• Surgery to excise the infected valve is often required in gram-negative
bacillus endocarditis, especially that caused by P. aeruginosa or when
infection involves the left-sided heart valves
• FUNGI  — No randomized, controlled studies have evaluated the
optimal therapy for fungal PVE. We, along with most infectious
disease specialists, recommend a combined approach that utilizes
both antifungal agents and valve replacement . Amphotericin B (daily
doses ranging from 0.7 to 1.0mg/kg per day) is the antimicrobial of
choice for treatment of fungal PVE as the greatest clinical experience
in treating fungal PVE is with this agent

147
• In the absence of clinical clues to a specific etiology, we along with
the AHA recommend that treatment for culture-negative PVE, with
onset within the first year following valve surgery, should
includevancomycin , gentamicin , cefepime , and rifampin  . The ESC
recommendations for this group omit cefepime . For initial therapy of
PVE with onset greater than one year after surgery, the AHA and the
ESC recommend treatment with ampicillin-sulbactam plus gentamicin
or vancomycin, gentamicin andciprofloxacin . The AHA recommends
the addition of rifampin to these regimens . For patients with the
onset of disease 12 months or more after valve implantation where
Bartonella is suspected, the AHA and we recommend treatment
with ceftriaxone , gentamicin, and doxycycline  . Aggressive efforts
must be made to identify a causative agent and specific therapy
defined, since treatment regimens for the causes of true blood
culture-negative endocarditis vary widely

148
Q fever endocarditis

• The minimum duration of therapy is 18 months

with doxycycline and hydroxychloroquine  . We do not prolong
treatment after three years unless there is no decrease of IgG
antibodies. Some recommend life-long therapy with doxycycline
following the initial combination treatment. There is a major risk of
sunburn, since tetracyclines and chloroquine are photosensitizing; as
a result, sun protection should be employed in such patients.

149
150
Valve dysfunction  — The outcome of PVE in patients who experience
moderate to severe heart failure due to prosthesis dysfunction is
improved if patients are treated surgically
•An unstable hypermobile prosthesis due to dehiscence of anchoring
sutures is a surgical emergency, requiring urgent intervention, because
the valve is likely to become increasingly unstable with acute severe
valve regurgitation.
•As with NVE, surgical intervention to correct valve dysfunction and
severe heart failure is associated with reduced mortality . Surgery must
be performed before heart failure becomes intractable. There is no
evidence that delaying surgery in this setting improves outcome or
reduces the frequency of recurrent endocarditis . In fact, the operative
mortality of these patients is proportional to the severity of
hemodynamic disability at the time of surgery

151
Patients with PVE complicated by perivalvular invasion experience high
mortality rates and are rarely curable with medical treatment alone. By
contrast, complex reconstructive procedures have been associated
with survival rates of 80 percent . Echocardiographic findings are
enhanced with transesophageal (versus transthoracic) but can still be
limited by "shadowing" from prosthetic valve sewing rings.
Echocardiographic findings of perivalvular invasion include :
•Valve dehiscence
•Perivalvular abscess
•Aortic aneurysm or pseudoaneurysm
•Fistula formation

152
• Relapse after optimal medical therapy  — If PVE relapses after
appropriate antimicrobial therapy, surgical intervention should
usually be performed since relapses often reflect unrecognized
perivalvular infection 

153
• Microorganisms usually requiring surgery  — Retrospective studies
suggest that S. aureus PVE is associated with significant mortality, up
to 70 percent in patients treated with antibiotics alone . While
mortality outcomes in patients who had surgery in these studies have
varied, intracardiac complications in patients with S. aureus PVE are
consistently associated with an increased mortality and surgical
intervention reduces mortality in this group

154
• Early surgical intervention is considered by most experts to be a
standard element of treatment for fungal PVE
• Patients who have fungal PVE have significant co-morbidities (such as
end-stage renal disease on hemodialysis or immunosuppressed states
from chemotherapy or HIV for example). Timing and duration of
medical therapy and surgical intervention are frequently complex.
• Some other pathogens, such as P. aeruginosa and probably multi-
resistant enterococci for which there is no synergistic bactericidal
regimen, are also less amenable to medical therapy. Surgery is
generally advised for PVE caused by these microorganisms.

155
• Embolization  — The frequency of embolic complications is higher in
patients with NVE who have vegetations exceeding 10 mm in
diameter compared to those with smaller vegetations. Comparable
data are not available for patients with PVE. The risk of emboli in this
setting, rather than constituting an indication for surgery, should be
weighed with other findings that might benefit from surgical
intervention and then factored into the overall management plan.
Recurrent emboli despite appropriate antibiotic therapy are an
indication for surgical intervention.

156
ESC recommendation  —

•  The European Society of Cardiology recommends emergent or

urgent surgery for PVE when there is severe valve dysfunction or
fistula formation and refractory pulmonary edema, cardiogenic
shock, or persisting heart failure. Urgent surgery is also advised for
uncontrolled infection (abscess, fistula), bacteremia persisting for 7
to 10 days, PVE caused by fungi or multiresistant organisms, and PVE
caused by staphylococci or gram-negative bacilli (especially if onset is
early after surgery). Similarly, for prevention of emboli after a prior
embolus, when there are other indications for surgery and
vegetations are large (>10 mm), or perhaps very large vegetations
(>15 mm) are present, urgent surgery is recommended. Surgery to
prevent emboli based on large vegetations alone is supported by
expert opinion only and relatively controversial . Surgery for
dehiscent, dysfunctional prosthetic valves in the absence of heart
failure can be elective.

157
• Following valve replacement for active bacterial endocarditis, the
Task Force on Infective Endocarditis of the European Society of
Cardiology (ESC) recommends another full course (six weeks) of
antimicrobial treatment if the intraoperative valve culture is positive .
We would agree with this approach for culture positive settings and
when an acute necrotizing process is found at surgery. If the culture is
negative and pathology does not indicate acute necrotizing infection,
we would agree with the ESC recommendations that the full
treatment course be completed (counting the duration of
preoperative antibiotics).

158
DEFINITIONS  — Complications of infective
endocarditis (IE) can be broadly categorized as:

• Cardiac
• Septic
• Embolic
• Neurologic
• Musculoskeletal
• Renal
• Associated with medical treatment

159
One can also consider complications in terms of their pathogenesis,
which leads to different groupings:
•Embolic (eg, cerebral infarct)
•Local spread of infection (eg, heart valve destruction)
•Metastatic infection (eg, vertebral osteomyelitis)
•Immune-mediated damage (eg, glomerulonephritis)

160
• CARDIAC COMPLICATIONS  — Cardiac complications are the most
common complications seen in infective endocarditis (IE), occurring
in one-third to one-half of patients in most recent case series
• heart failure  — Heart failure (HF) remains the most common cause
of death due to IE in the modern era and is the most frequent reason
for cardiac surgery in patients with IE
• The usual cause of HF in patients with IE is valvular insufficiency
resulting from infection-induced valvular damage. Rarely, embolism
of fragments of valvular vegetations or vegetation-induced stenosis
of the coronary ostia can cause acute myocardial infarction and
subsequent HF

161
• Perivalvular abscesses  — Among patients with IE, the reported
incidence of perivalvular abscess at surgery or autopsy has ranged
from about 30 to 40 percent . The aortic valve and its adjacent
annulus are more susceptible to abscess formation and the
complications of perivalvular extension of infection than are the
mitral valve and ring Perivalvular abscesses can extend into adjacent
cardiac conduction tissues, possibly leading to various forms of heart
block. Involvement of the conducting system is most common with
infection of the aortic valve, especially when there is involvement of
the valve ring between the right and non-coronary cusp (this
anatomic site overlies the intraventricular septum that contains the
proximal ventricular conduction system). Rarely perivalvular infection
can result in extrinsic coronary compression and can cause acute
coronary syndrome

162
• Perivalvular abscess should be suspected when fever persists despite
appropriate antimicrobial therapyand/or when conduction
abnormalities appear on the ECG

163
• Other extravalvular complications  — Other rare extravalvular
cardiac complications of IE include:
• Pericarditis, which may be suppurative or nonsuppurative, can rarely
cause pain or even cardiac tamponade 
• Fistulous intracardiac connections (eg, aorta-atrial or aorta-
ventricular) due to extension of infection from the valve to adjacent
myocardium may rarely result in large aneurysms, a pseudoaneurysm
if the aortic wall is involved , or even myocardial perforation

164
Emboli

• consisting of vegetation fragments can occlude or damage virtually any

blood vessel, large or small, in the systemic or pulmonary arterial circulation.
As a result, emboli can produce:
• 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
• The incidence of cerebral emboli detected in patients with IE undergoing
magnetic resonance imaging (MRI) is markedly higher than the incidence of
emboli detected on the basis of clinical signs and symptoms

165
• The size of a vegetation as determined by echocardiography has been
assessed as a risk factor for clinical findings of embolization in
patients with IE. Although some data are conflicting, vegetation size
is generally a risk factor for embolization.
• However, the presence or absence of vegetations, the location of the
vegetations, the characteristics of vegetations by TEE, the specific
etiologic microorganism, or antiphospholipid antibodies may also
have predictive value

166
• NEUROLOGIC COMPLICATIONS  — Symptomatic cerebrovascular
complications occur in about 35 percent of patients . Silent
cerebrovascular complications (including ischemia and
microhemorrhage) may occur in up to 80 percent of patients

167
• Manifestations  — 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)

168
• MYCOTIC ANEURYSMS  — Mycotic aneurysms can occur in the
cerebral or systemic circulation of patients with infective endocarditis
(IE), usually at points of vessel bifurcation

169
• RENAL DISEASE  — Renal infarction (due to emboli), drug-induced
acute interstitial nephritis, glomerulonephritis (due to deposition of
immunoglobulins and complement in the glomerular membrane)
and, rarely, renal abscess can occur in patients with infective
endocarditis (IE)

170
• Acute renal failure, defined as a serum creatinine of
2 mg/dL (177 µmol/L) or greater, has been reported in up to one-
third of patients . By contrast, chronic renal failure due to immune-
complex mediated glomerulonephritis, which was a common
contributing cause of death in patients who presented with classic IE
in the preantibiotic era, is now rare. Immune complex-mediated renal
disease is also uncommon in the antibiotic era, especially in patients
whose infection is detected and treated early.

171
• METASTATIC ABSCESSES  — Rarely, metastatic abscesses develop in
the kidneys, spleen, brain, or soft tissues (eg, the psoas muscle) in
the setting of infective endocarditis (IE).
• There is a strong association between IE and splenic abscess, even
though otherwise splenic abscesses are less frequently observed
than other types of intraabdominal abscesses. Patients with splenic
abscesses usually do not have marked abdominal pain or
splenomegaly; persistent fever during or after treatment for IE and
occasionally recurrent bacteremia after cure of the valvular infection
may be the only clues to the presence of this complication

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• MUSCULOSKELETAL COMPLICATIONS  — Vertebral osteomyelitis is a
well known but relatively rare complication of infective endocarditis
(IE). Although the majority of patients with IE and back pain do not
have vertebral osteomyelitis, protracted, severe back pain in any
patient with IE should alert the clinician to this possibility. Plain films
are insensitive for diagnosing vertebral osteomyelitis, especially if
taken early in the course of illness

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• Osteomyelitis more frequently complicates S. aureus endocarditis
than IE due to other microorganisms .
• Acute septic arthritis, involving one or more joints, may be the first
clue to the presence of IE in a small percentage of patients. IE should
be strongly considered in selected cases of septic arthritis:
• When infections spontaneously arise in joints of the axial skeleton
(eg, sacroiliac, pubic, or manubriosternal joints).
• When organisms with a known propensity to cause IE (eg, S. aureus,
viridans streptococci or non-group A beta-hemolytic streptococci)
grow from a joint aspirate, particularly in patients without a history
of recent surgery, joint infection, or trauma.
• When multiple joints are infected.

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Predictors of death  — Several studies have attempted to identify
predictors of death in patients with infective endocarditis (IE). Each
patient may have one or more of the following:

• Infection with S. aureus ; mortality is lower with streptococcal infection (8

versus 33 percent with S. aureus in one series)
• Heart failure
• Diabetes mellitus
• Embolic events
• Perivalvular abscess
• Larger vegetation size
• Female gender
• Contraindication to surgery
• Low serum albumin
• Persistent bacteremia
• Abnormal mental status
• Poor surgical candidac

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• THEORETICAL BASIS FOR PROPHYLAXIS  — The pathogenesis of
infective endocarditis (IE) is presumed to involve the following
sequence of events :
• Formation of a small noninfected thrombus on an abnormal
endothelial surface
• Secondary infection of this nidus with bacteria that are transiently
circulating in the bloodstream
• Proliferation of bacteria resulting in the formation of vegetations on
the endothelial surface
• Since the occurrence of bacteremia is crucial to the initiation of an
episode of IE, it is theoretically reasonable to conclude that
preventing or promptly treating transient bacteremia will prevent the
above sequence even if a predisposing valvular lesion is present.

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Patients at highest risk  — Prophylaxis was recommended only in those
settings associated with the highest risk of developing an adverse outcome if
IE was to occur . Patients with the following cardiac conditions were
considered to meet this criterion:
•Prosthetic heart valves, including bioprosthetic and homograft valves.
•Prosthetic material used for cardiac valve repair
•A prior history of IE.
•Unrepaired cyanotic congenital heart disease, including palliative shunts and
conduits.
•Completely repaired congenital heart defects with prosthetic material or
device, whether placed by surgery or by catheter intervention, during the first
six months after the procedure.
•Repaired congenital heart disease with residual defects at the site or adjacent
to the site of the prosthetic device.
•Cardiac "valvulopathy" in a transplanted heart. Valvulopathy is defined as
documentation of substantial leaflet pathology and regurgitation

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• Procedures that may result in transient bacteremia  — The 2007
AHA guidelines recommend that antimicrobial prophylaxis be given
to patients with the cardiac lesions cited above when they undergo
procedures likely to result in bacteremia with a microorganism that
has the potential ability to cause endocarditis 

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• Dental  — The risk of IE is generally considered to be the highest for
dental procedures that involve manipulation of gingival tissue or the
periapical region of the teeth, or perforation of the oral mucosa; this
does not include routine cleaning
• All individuals at risk for developing IE should establish and maintain
a program of oral health care including regular professional care, the
regular use of manual or powered toothbrushes, dental floss, and
other plaque removing devices.
• Respiratory tract  — Although a variety of organisms may cause
bacteremia during respiratory tract procedures, there is no direct
evidence that such bacteremias cause IE. The AHA guideline does not
recommend routine antimicrobial prophylaxis for procedures unless
they involve incision or biopsy of the respiratory tract mucosa .
Examples of such procedures include tonsillectomy, adenoidectomy,
or bronchoscopy with biopsy.

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• In patients who undergo an invasive respiratory tract procedure as
part of the treatment of an established infection:
• The ongoing antibiotic regimen should include an agent that is active
against viridans group streptococci.
• In patients who have a respiratory tract infection that is known or
suspected to be caused by Staphylococcus aureus, the regimen
should include an agent active against S. aureus.

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• Genitourinary and gastrointestinal tracts  — The risk of bacteremia
is significantly lower for invasive genitourinary (GU) procedures such
as dilation of strictures, insertions of catheters, and prostatectomy
compared with dental or respiratory tract infections. Invasive
gastrointestinal (GI) procedures, such as lower bowel endoscopy with
biopsy or endoscopic retrograde cholangiopancreatography, have an
even lower risk of IE since bacteremia due to organisms capable of
causing endocarditis occurs in less than 5 to 10 percent of cases.
• The AHA guidelines no longer consider any GI (including diagnostic
colonoscopy or esophagogastroduodenoscopy) or GU procedures
high risk and therefore do not recommend routine use of IE
prophylaxis even in patients with the highest risk cardiac conditions
defined above [ 2 ]. Data evaluating the risk of IE associated with GI
endoscopy are discussed in detail elsewhere.

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• Some patients with established infections of the GI or GU tract may
have enterococcal bacteremia. For patients with the highest risk
cardiac conditions who have ongoing GI or GU tract infection or who
are undergoing a procedure for which antibiotic therapy to prevent
wound infection or sepsis is indicated, the AHA suggests an antibiotic
regimen that includes an agent active against enterococci

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• Vaginal or cesarean delivery  — Vaginal or cesarean delivery is not an
indication for routine antibiotic prophylaxis since the rate of
bacteremia with these procedures is low . The 2007 AHA guidelines
specify that prophylaxis is not indicated for vaginal delivery or
cesarean section , and the 2008 AHA/ACC guidelines note that
antibiotic prophylaxis is not recommended for genitourinary
procedures .
• The American College of Obstetricians and Gynecologists (ACOG),
Committee on Obstetic Practice has endorsed the 2007 AHA
recommendations, noting that infective endocarditis prophylaxis is
not recommended for vaginal or cesarean delivery in the absence of
infection

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• Skin or musculoskeletal tissue  — Patients with infected skin, skin
structure, or musculoskeletal tissue may have polymicrobial
infections. When such patients undergo a surgical procedure, only
bacteremia with staphylococci or beta-hemolytic streptococci are
likely to cause IE. The appropriate antibiotic regimen is discussed
below.
• NICE guideline  — The United Kingdom National Institute for Health
and Clinical Excellence (NICE) published a guideline in 2008
recommending that NO antimicrobial prophylaxis for IE be
administered prior to dental or other invasive procedures . In the two
years following the issuance of these guidelines, a ‘before and after’
study noted a 78 percent reduction in antibiotic prophylaxis
prescriptions after the guidelines were introduced, with no significant
increase in the incidence of infective endocarditis

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AHA

Table 6. Summary of Major Changes in Updated Document

We concluded that bacteremia resulting from daily activities is much
more likely to cause IE than bacteremia associated with a dental
procedure.
We concluded that only an extremely small number of cases of IE
might be prevented by antibiotic prophylaxis even if prophylaxis is
100% effective.
Antibiotic prophylaxis is not recommended based solely on an
increasedlifetime risk of acquisition of IE.
Limit recommendations for IE prophylaxis only to those conditions
listed in

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Antibiotic prophylaxis is no longer recommended for any other form of
CHD, except for the conditions listed
Antibiotic prophylaxis is reasonable for all dental procedures that
involve manipulation of gingival tissues or periapical region of teeth or
perforation of oral mucosa only for patients with underlying cardiac
conditions associated with the highest risk of adverse outcome from IE
Antibiotic prophylaxis is reasonable for procedures on respiratory tract
or infected skin, skin structures, or musculoskeletal tissue only for
patients with underlying cardiac conditions associated with the highest
risk of adverse outcome from IE

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Antibiotic prophylaxis solely to prevent IE is not recommended for GU
or GI tract procedures.
Although these guidelines recommend changes in indications for IE
prophylaxis with regard to selected dental procedures (see text), the
writing group reaffirms that those medical procedures listed as not
requiring IE prophylaxis in the 1997 statement remain unchanged and
extends this view to vaginal delivery, hysterectomy, and tattooing.
Additionally, the committee advises against body piercing for patients
with conditions listed because of the possibility of bacteremia, while
recognizing that there are minimal published data regarding the risk of
bacteremia or endocarditis associated with body piercing.

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• Among patients who undergo cardiac valve replacement,
approximately 60 percent receive mechanical valves composed of
carbon alloys with a tilting disk or bileaflet design. The remaining 40
percent receive bioprosthetic valves, which may be heterografts,
composed of porcine or bovine tissue, homografts, which are
preserved human aortic valves, or pulmonary autografts

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• There are five main issues for managing and advising the patient with
a prosthetic heart valve:
• Antithrombotic therapy to prevent valve thrombosis and
thromboembolism
• Evaluation of valve function
• Endocarditis prophylaxis
• Safety of exercise
• Pregnancy

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• ANTITHROMBOTIC THERAPY  — Antithrombotic therapy
with warfarin (or other vitamin K antagonist) and/or aspirin is
recommended in patients with prosthetic heart valves to prevent
valve thrombosis and thromboembolic events. Recommendations for
therapy vary with the type of valve (the risk is much greater with
mechanical valves), the site of valve replacement (the risk is greater
with mitral than aortic valves), the presence or absence of underlying
risk factors for thrombus formation, and certain clinical settings, such
as pregnancy and surgical procedures. The benefits of
anticoagulation therapy must be weighed against the risk of bleeding,
particularly intracranial bleeding

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• SERIAL MONITORING OF VALVE FUNCTION  — The incidence of late
structural failure varies among the different types of prosthetic heart
valves. Most current mechanical valves can be expected to last 20 to
30 years or more. In contrast, 10 to 20 percent of human aortic
homograft prostheses, and 30 to 35 percent of porcine heterograft
prostheses fail within 10 to 15 years of implantation . The failure rate
with porcine valves is higher with mitral compared to aortic valves
(eg, 36 versus 15 percent at 11 years in the Veterans Administration
Cooperative Study) 

191
• Patients with prosthetic heart valves are at high risk for endocarditis
and should use prophylactic antibiotics in accordance with current
guidelines

192
• Regular moderate exercise to maintain cardiovascular fitness is encouraged.
Issues related to participation in competitive sports were addressed by the
36th Bethesda Conference; the recommendations vary with the type and
location of the prosthetic heart valve and the intensity and type of exercis:
• Patients with a bioprosthetic mitral valve who have normal valve function,
normal or near-normal left ventricular function, and are not being treated
with anticoagulation can participate in low and moderate static and dynamic
competitive sports (class IA, IB, IIA, and IIB) ( figure 1 ).
• Patients with a mechanical or bioprosthetic aortic valve who have normal
valve and left ventricular function can participate in low and moderate static
and low and moderate dynamic competitive sports (class IA, IB, and IIA) .
• Patients participating in more than low-intensity sports (class IA) should
undergo exercise testing to at least the level of activity attained in
competition to evaluate both exercise tolerance and symptom and
hemodynamic responses.
• Independent of the above considerations, patients treated with
anticoagulation should not participate in sports associated with the risk of
bodily contact or the danger of trauma

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• PREGNANCY  — Pregnancy in women with prosthetic heart valves is
complicated by the need for antithrombotic therapy to prevent valve
thrombosis and thromboembolism. Warfarin exposure between the
sixth and twelfth week of gestation can cause a specific embryopathy
affecting cartilage and bone. Warfarin embryopathy has an estimated
incidence of 5 to 7 percent, although reported ranges vary and
appear to correlate with the dose. Heparin does not cause
embryopathy but is associated with a higher risk of valve thrombosis.

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INTRODUCTION — Prosthetic heart valves
can be classified as mechanical or biological
Mechanical valves are those that are manufactured entirely from
manmade materials; these valves typically have a tilting disk or bileaflet
design and are composed of carbon alloys.
Biological valves are composed primarily of material that originated as
living tissue, including porcine aortic valves, valves manufactured from
bovine pericardium, valves transplanted from other human beings
(homografts), and autografts from the patient.
Prosthetic heart valves are associated with a variety of complications:
Structural deterioration, particularly with bioprosthetic valves
Valve obstruction due to thrombosis or pannus formation
Systemic embolization
Bleeding
Endocarditis and other infections
Left ventricular systolic dysfunction, which may be pre-existing
Hemolytic anemia 195
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 REFERENCE
1. Harrison’s Principles of Internal
Medicine, 16th ed., 2005
2. UpToDate online reverences
3. American Heart Association,
guidelines on management of Infective
Endocarditis

198