Transcript Endocarditis

Infective Endocarditis
National Institutes
of Health
National Institute of
Allergy and Infectious
Diseases
Talk Outline
History
Epidemiology
Pathophysiology
Risk factors
Clinical presentation
Causes
How to diagnose
Treatment
Special groups
Alois Alzheimer
Alois Alzheimer
1906 identified an 'unusual disease of the cerebral cortex' which caused
memory loss, disorientation, hallucinations and ultimately death and was
associated with cerebral plaques and neurofibrillary tangles.
Alois Alzheimer
1906 identified an 'unusual disease of the cerebral cortex' which caused
memory loss, disorientation, hallucinations and ultimately death and was
associated with cerebral plaques and neurofibrillary tangles.
Died in 1915 (age 51) from endocarditis.
Orville Gibson
Orville Gibson
Guitar manufacturer.
Orville Gibson
Guitar manufacturer.
Died in 1918 (age 62) from endocarditis.
Gustav Mahler
Gustav Mahler
Composer.
Mahler died on May 18, 1911, at age 50 from endocarditis.
He never heard the Ninth Symphony performed .
The Ninth tale
By Kevin Berger / SALON
Why was infective endocarditis such
a bad disease in the early 1900s?
Why was infective endocarditis such
a bad disease in the early 1900s?
No antibiotics
No cardiac surgery
Is infective endocarditis still a
problem now?
Is infective endocarditis still a
problem now?
YES
● AHA estimates there are 10,000-20,000 cases per year in the U.S.
● The incidence of disease (about 5 cases/100,000 pt years) has not
changed in several decades!!
● Mortality is 20-30% at 1 year (for GNRs and fungi is 50%)
Most common valves:
Mitral valve (40%), Aortic valve (36%), then multivalvular.
R sided <10% of all cases.
BUT, endocarditis is NOT the same
disease it was a century ago.
“Almost all aspects of the disease, including its
natural history, predisposing factors, sequelae, and
causative organisms, are virtually unrecognisable
compared with Osler’s original descriptions from
the 19th century.”
B.D. Prendergast Heart 2006;92;879-885.
Reasons IE remains a problem and why
its clinical manifestations have changed
 less rheumatic heart disease
 more degenerative valve disease in the elderly
 replacement valves
 intravenous drug use
 vascular instrumentation
 resistant bacteria
 earlier diagnosis
 detection of previously unknown pathogens
Pathophysiology
Damaged epithelium results in exposed stromal cells and extracellular
matrix proteins.
This triggers deposition of fibrin-platelet clots.
Streptococci can bind to fibrin-platelet clots and Staphylococcus aureus can bind
to beta-1 integrins expressed by inflamed endothelial cells.
Heart 2006;92;879-885.
Pathophysiology
Endothelial disruption also results in coagulation at site of defect.
Bacteria bind to the clot.
Cycle of monocyte activation and cytokine release contribute to a progressive
inflammation and enlargement of the infected vegetation.
Local extension and tissue damage may result in abscess formation.
Ultimately septic emboli may disseminate to brain, spleen, and kidney.
Heart 2006;92;879-885.
Pathophysiology
Endothelial Damage
Thrombus
Bacterial Seeding
Maturation of vegetation
(deposition of fibrin, proliferation of bacteria)
Pathophysiology
Endothelial Damage
Thrombus
Bacterial Seeding
Maturation of vegetation
(deposition of fibrin, proliferation of bacteria)
Why is endocarditis so difficult to Rx?
Pathophysiology
Endothelial Damage
Thrombus
Bacterial Seeding
Maturation of vegetation
(deposition of fibrin, proliferation of bacteria)
Why is endocarditis so difficult to Rx?
absence of vasculature makes delivery of Abx to bacteria within mature
vegetation difficult
Risk factors for infective endocarditis?
Risk factors for infective endocarditis?
● underlying heart disease
-degenerative aortic and mitral valve disease
-rheumatic heart dz (less common)
● prosthetic valve or prior valve surgery
● previous infective endocarditis
● IVDU
● iatrogenic or nosocomial infection
prior dental surgery?  risk likely overemphasized
NOTE: in one recent study 47% of patients with infective endocarditis had no
previous knowledge of an underlying cardiac disorder.
JAMA 2002;288:75-81.
Clinical Presentation of IE
-SYMPTOMS-
Clinical Presentation of IE
-SYMPTOMS-FEVER (90% of pts, but may be absent  esp in elderly)
-Chills
-Sweats
-Poor appetite
-Weight loss
NOTE: emboli to brain, spleen, or lung occur in 30% of patients and
are often the presenting symptom
Focal neurologic change if septic embolus to CNS OR if development
of a mycotic aneurysm
Cough/SOB/chest pain if septic embolus to lungs
Abdominal pain if septic embolus to spleen
Clinical Presentation of IE
-SIGNS-
Clinical Presentation of IE
-SIGNS-
-HEART MURMUR (85%)
-Cutaneous manifestations of DIC
-Focal neurologic deficits
-Embolic phenomena
Roth spots
Janeway lesions
Osler’s nodes
distal infarcts of digits
Purpuric lesions on the arm of a woman
with staphylococcal endocarditis.
Roth spots: “white-centered” hemorrhages. Likely are microinfarcts. In
addition to endocarditis, occur in HTN, HIV, connective tissue disease,
severe anemia, Behçet's disease, viremia, & hypercoagulable states.
Osler’s nodes
-small hemorrhages with
nodular quality on fingers,
palms, and soles
-very uncommon
-likely septic emboli
(could culture these)
Merk Medicus online
-no real difference between these and Janeway
lesions (some say Osler’s nodes on digit tips and
tender and Janeway lesions on palms/soles and
non-tender)
Note: Mahler, who had streptococcal endocarditis, developed septic
abscesses all over his body. We just don’t see this anymore.
What about splinter hemorrhages?
What about splinter hemorrhages?
Splinter hemorrhages have been reported in up to 66% of all
hospital admissions and in up to 56% of all healthy adults.
(Sapira 1996)
splinter hemorrhages
Merk Medicus online
Clinical Presentation of IE
-LAB VALUES-
Clinical Presentation of IE
-LAB VALUES-
Nothing particularly helpful.
-Elevated ESR or CRP
-May have elevated WBC count as well as other
changes in CBC.
-May see changes c/w glomerulonephritis
(due to immune complex deposition and/or septic emboli)
So, how is the prognosis for patients
diagnosed with infective
endocarditis?
So, how is the prognosis for patients
diagnosed with infective
endocarditis?
Not good.
ANNUAL MORTALITY FROM INFECTIVE
ENDOCARDITIS APPROACHES 40%.
Arch Intern Med 2002;162:90-4.
Clinical complications of IE
HEART
heart failure
perivalvular abscess
pericarditis
Ao valve dsxn
BRAIN
abscess
meningitis
encephalopathy
hemorrhage
KIDNEY
infarct
abscess
glomerulonephritis
OTHER
vertebral osteomyelitis
septic arthritis
metastatic abscesses
NNMC case from 8/07
(with thanks to Dr. Mark Johnson)
31yo M
Symptoms for a few weeks, dental procedure 2
months prior
Fevers
HA
Homonymous hemianopsia
+ MURMUR (and possible Osler’s node)
TTE  large MV anterior leaflet vegetation
BlCx’s positive with Streptococcus mitis
Brain MRI c/w L MCA septic embolism
Treated with PCN/gent and, developed heart
failure from mitral regurgitation
Taken to OR
Had a mechanical valve placed.
Placed on anticoagulation.
Had a cerebral angiogram done which showed a
4mm right sided parietal “mycotic” (really, “infected”
aneurysm). That vessel was then closed/filled with
a glue by interventional neurology.
Morbidity in this 31 yo pt
Morbidity in this 31 yo pt
1. Stroke causing loss of vision
2. Infected brain aneurysm that required interventional
embolization that may still have chance of bleeding.
3. In-hospital stay for >1 month with long course of Abx.
4. Had to undergo open heart surgery and now has a
mechanical valve which
will probably need to be changed at some point
high risk for endocarditis
5. On life-long anticoagulation.
Because this is a highly morbid disease and
because the clinical presentation is usually
pretty non-focal (fever and chills), what is the
best thing we can do on exam to help us think
about the possibility of endocarditis?
Because this is a highly morbid disease and
because the clinical presentation is usually
pretty non-focal (fever and chills), what is the
best thing we can do on exam to help us think
about the possibility of endocarditis?
 Do a careful examination for a
heart murmur in all patients with
fever.
Etiologic agents of IE
Etiologic agents of IE
Agent
Streptococci
Viridans streptococci
Enterococci
other streptococci
Staphylococci
coagulase +
coagulase Aerobic GNRs
Fungi
Miscellaneous bacteria
Culture Negative
Cases (%)
70%
35%
10%
20%
20%
18%
2%
5%
2%
<5%
<5-25%
Agents that make you think of
endocarditis when they grow in the blood
Agent
Streptococcus mutans
Streptococcus bovis
Streptococcus mitior
Streptococcus sanguis
Unclassified viridans strep
Endocarditis/non-endocarditis
14:1
6:1
3:1
3:1
1.4:1
Adapted from PPID
AND….when we diagnose which organism from a line infection?
Agents that make you think of
endocarditis when they grow in the blood
Agent
Streptococcus mutans
Streptococcus bovis I
Streptococcus mitior
Streptococcus sanguis
Unclassified viridans strep
Endocarditis/non-endocarditis
14:1
6:1
3:1
3:1
1.4:1
Adapted from PPID
AND….Staphylococcus aureus in the setting of a line infection
S. aureus line infection carries a 22% likelihood of endocarditis.
How to diagnose endocarditis
How to diagnose endocarditis
BLOOD CULTURES!!!!
Three sets of PERIPHERALLY drawn blood cultures drawn
one hour apart before the introduction of antibiotics.
How much to draw?
How to diagnose endocarditis
If antibiotics were started before adequate blood cultures
were drawn, what can be done to make a microbiologic dx?
How to diagnose endocarditis
If antibiotics were started before adequate blood cultures
were drawn, what can be done to make a microbiologic dx?
Strongly consider stopping antibiotics for 24-48 hours and
then obtaining blood cultures.
How else to diagnose endocarditis
How else to diagnose endocarditis
ECHOCARDIOGRAPHY
Classic finding is of an oscillating intracardiac mass on
a valve or in the path of a regurgitant jet.
Other possible findings: abscess, dehiscence of a
prosthetic valve, aneurysm, fistula, leaflet perforation.
What kind of ECHO?
What kind of ECHO?
TEE  93% sensitive
TTE  46% sensitive
Both are very specific.
Diagnostic value of harmonic transthoracic
echocardiography in native valve infective endocarditis:
comparison with transesophageal echocardiography
Davinder S Jassal,
1,2 Amin Aminbakhsh,1 Tielan Fang,2 Nasir Shaikh,1 John M Embil,3 Gordon S Mackenzie,4 and James W Tam1
2007
The sensitivity for the detection of
vegetations by hTTE was 84%
Modified Duke criteria
Minor Criteria
Definite infective endocarditis
-Pathological criteria positive
-Two major criteria
-One major and three minor
-Five minor criteria
-Prior heart dz
-Fever
-Immunological phenomena
(GN, Osler’s nodes, Roth spots)
-Increased CRP or ESR
-Vascular phenomena
(emboli, petechiae, purpura, splinters)
-Microbiological data not fitting major
criteria
Major Criteria
-2 + BlCxs with typical endocarditis organisms
(Viridans strep, S. bovis,
HACEK, S. aureus, enterococcus)
-2 +BlCxs taken >12hrs apart for other bacteria
-Single + BlCx or positive serology for Coxiella
-Positive echo showing moving structures, abscess, new regurgitation, other
Treatment of Infective Endocarditis is
multidisciplinary
(primary team, surgical team, micro dept)
ABX
(typically 6 weeks from time of negative cultures)
+
possible surgery
What antibiotics to give?
http://www.idsociety.org/pg/toc.htm
Indications for surgery
Some indications for surgery
• ≥1 embolic events during 1st two weeks of Abx
• Increasing vegetation size or + BlCxs despite Abx
• Heart failure unresponsive to medications
• Valve perforation/rupture, dehiscence
• New heart block
• Large abscess
• Organism known to be difficult to Rx with Abx alone
(Candida, Pseudomonas)
About 40% of all patients with endocarditis go to surgery
What if the blood cultures are negative?
(this occurs about 15% of the time)
Reasons this occurs:
What if the blood cultures are negative?
(this occurs about 15% of the time)
Reasons this occurs:
1. slow-growing bacteria (ex Coxiella and
Bartonella species)
2. Nonbacterial organisms (eg fungi)
3. Antibiotic administration preceding blood
cultures
Culture negative endocarditis
CAUSES
• Nutritionally-variant streptococci
• Fastidious GNR of HACEK group
Haemophilus parainfluenza, aphrophilus, paraphrophilus, influenza
Aggregatibacter actinomycetemcomitans
Cardiobacterium hominis
Eikenella corrodens
Kingella kingae and denitrificans
• Brucella species
• Coxiella burnetii
• Bartonella species
• Chlamydia species
• Legionella species
• Mycoplasma species
• Tropheryma whipplei
• Fungi (Candida, Histoplasma, and Aspergillus)
Culture negative endocarditis
CAUSES
Nutritionally-variant streptococci
Fastidious GNR of HACEK group
Haemophilus parainfluenza, aphrophilus, paraphrophilus, influenza
Actinobacillus actinomycetemcomitans
Cardiobacterium hominis
Eikenella corrodens
Kingella kingae and denitrificans
Brucella species
Coxiella burnetii
Bartonella species
Chlamydia species
Legionella species
Mycoplasma species
Tropheryma whipplei
Fungi (Candida, Histoplasma, and Aspergillus)
C. burnetii in 167 cases (48 percent)
Bartonella spp in 99 cases (28 percent)
Streptococci in 4 cases
Tropheryma whipplei in 2 cases
Abiotrophia elegans in 1 case
Mycoplasma hominis in 1 case
Legionella pneumophila in 1 case
Escherichia coli in 1 case
Culture negative endocarditis
WORK-UP
First thing to do?
Culture negative endocarditis
WORK-UP
Step 1: Talk to the microbiology lab 
Culture negative endocarditis
WORK-UP
Step 1: Talk to the microbiology lab 
hold BlCxs for 3-4 weeks
lysis centrifugation culture tubes
good for fungi and Bartonella
shell vial culture tubes
good for Coxiella, Bartonella, T. whipplei, and Brucella
special medias
blind sub onto chocolate agar
Nutritionally-variant streptococci  blood culture
Fastidious GNR of HACEK group  Long term blood CX
Haemophilus parainfluenza, aphrophilus, paraphrophilus, influenza
Actinobacillus actinomycetemcomitans
Cardiobacterium hominis
Eikenella corrodens
Kingella kingae and denitrificans
Brucella species  blood culture, serology; Cx, IH and PCR of tissue
Coxiella burnetii serology; Cx, IH and PCR of tissue
Bartonella species blood culture, serology; Cx, IH and PCR of tissue
Chlamydia species  serology; Cx, IH and PCR of tissue
Legionella species  blood culture, serology, UAg; Cx, IH, and PCR of tissue
Mycoplasma species serology; Cx, IH and PCR of tissue
Tropheryma whipplei  IH and PCR of tissue
Fungi (Candida, Histoplasma, and Aspergillus)  blood culture
IH = immunohistology
Culture negative endocarditis
Empiric therapy?
Culture negative endocarditis
Empiric therapy?
 Try to tailor therapy to the organisms
for which the patient is most at risk
Reasons we REALLY want to know the organism
Recommended regimens for Cx negative endocarditis
Native valve
amp/sulbactam + gentamicin
OR
vancomycin + gentamicin + ciprofloxacin
Prosthetic valve
vancomycin + gentamicin + cefepime + rifampin
Suspected Bartonella
Ceftriaxone + gentamicin + doxycyline
keep in mind, these don’t take into account our high
rate of community acquired MRSA
At the end of antibiotic therapy,
re-evaluate valve by
echocardiography
IE –special groups
What type of heart infection causes this
image on CT?
IE –special groups
IVDU
•Endocarditis risk 1-5% per year
•Infection often right sided (50% of time)
•Staphylococcus aureus is most common pathogen
Prosthetic valves
•Endocarditis risk 0.1-2.3% PER YEAR
•NEED TEE to evaluate
•Staphylococci predominate early
•Late, infxs spectrum resembles that of naïve valves
•Complications common (esp Ao root abscess)
•Mortality >40%
IE – Prevention (2007 AHA guidelines)
Recommendations revised b/c
● Endocarditis more likely from frequent exposure to random bacteremias from
daily activities than from dental/GI/GU procedures.
TRANSIENT BACTEREMIA
Tooth extraction: 10-100%
Peridontal surgery 40-90%
Teeth cleaning 40%
Tooth brushing/flossing: 20-70%
Wooden toothpicks: 20-40%
Chewing food: up to 50%
● Prophylaxis likely protects an exceedingly small, if any, cases of endocarditis.
To reduce risk of bacteremia from dental procedures: MAINTAIN GOOD ORAL HEALTH
IE – Prevention (2007 AHA guidelines)
Prophylaxis ONLY for high-risk patients
1) prosthetic heart valve
2) previous infective endocarditis
3) complex congenital heart disease
4) valvulopathy after heart transplant
ONLY prior to dental procedures involving
manipulation of gingival tissue
or periapical region of teeth
or perforation of oral mucosa
Single dose 30-60min b/f
oral
amoxicillin 2 g
cephalexin 2g
clindamycin 600mg
azithromycin 500mg
iv
ampicillin 2g
cefazolin or ceftriaxone 1g
clindamycin 600mg
NOT prior to GI or GU procedures
Also NOT for intubation, cardiac cath, pacer placement, TEE
JACC 2008 v52 (8) 676-85
Take home points
• a common, highly lethal infection
• signs: fever and murmur
• get TEE in pts that develop S. aureus line infections
• get ECHO and draw 3 sets of large volume blood cultures
OFF abx in patients suspected of endocarditis
• talk with the microbiology lab and the surgeons
In the summer of 1896, the German conductor Bruno Walter
visited Mahler in the Austrian alps and gazed up at the steep
cliffs. The bold composer told his young acolyte not to bother
looking at them. "I have already composed that all away," he
said. He was referring to his Third Symphony, with its
exhilarating peaks of cellos and basses, rushing river of
trumpets and trombones.