Infective Endocarditis

Irsad Andi Arso

Faculty of Medicine Gadjah Mada
University

Objectives
Describe the incidence of IE in various
heart conditions.
Review the Duke criteria of infective
endocarditis
Review the indications for prophylaxis and
current recommendations for antimicrobial
therapy.
Review the efficacy and controversies in
IE prophylaxis.

Background
Relatively rare in children
Pre-antibiotic era: mortality was nearly
100%
Mortality approaches 15-25%

Epidemiology
Increasing incidence beginning in the 80s
Increasing number of surgical patients
Increasing number of complex congenital
heart disease
Increased use of prosthetic materials
NICUs and PICUs

Pathogenesis, Part 1
Damaged endothelium
undamaged endothelium not conducive to
bacterial colonization
endothelium can be damaged by high-velocity
flows
trauma to endothelium can induce
thrombogenesis, leading to nonbacterial
thrombotic endocarditis (NBTE). NBTE is
more receptive to colonization

Heart disease and IE

Disease
Acyanotic Heart Disease
VSD
Aortic stenosis
PDA
Coarctation of the aorta
Pulmonary stenosis
VSD with other defects
Atrioventricular septal defect
Mitral valve abnormality
Atrial septal defect
Mitral valve prolapse
Cyanotic Heart Disease
Tetralogy of Fallot
Transposition of Great Vessels
Tricuspid Atresia
Rheumatic Heart Disease
No Heart Disease

No.

194
89
25
25
21
18
16
16
11
8

21.8
10.0
2.8
2.8
2.4
2.0
1.8
1.8
1.2
0.9

143
35
9
86
75

16.0
3.9
1.0
9.7
8.4

Berkowitz, FE: Infective endocarditis. IN Nichols EG, Cameron DE, Greeley WJ, et al (eds):
Critical Heart Disease in Infants and Children. St. Louis, Mosby-Year Book, 1995.

Pathogenesis, Part 2
Microorganism

No.

Streptococcus viridans

289

31.3

Staphylococcus aureus

225

24.4

Negative cultures

152

16.4

Other streptoccal species (e.g. enterococci)

55

5.9

HACEK and diphtheroids

50

5.4

Gram negative bacilli

45

4.8

Strept pneumoniae

18

1.9

Fungi

14

1.5

Others

28

3.0

Berkowitz, FE: Infective endocarditis. IN Nichols EG, Cameron DE, Greeley WJ, et al (eds):
Critical Heart Disease in Infants and Children. St. Louis, Mosby-Year Book, 1995.

Microbiology
S. Viridans
Most common causative organism

Gram negative bacilli

Neonates and immunocompromised patients

Prosthetic valves
Within first year of surgery: Coag-negative staph
After first year: similar to native valve endocarditis

HACEK organisms
Hemophilus, Actinobacillus, Cardiobacterium, Eikenella,
Kingella
Frequently affect damaged valves and can cause emboli

Diagnosis
Traditionally based upon positive blood
cultures in the presence of a new or
changing heart murmur, or persistent
fever in the presence of heart disease.
Shortcomings include culture-negative
endocarditis, lack of typical
echocardiographic findings, etc.

Duke Criteria
Based on pathological and clinical criteria.
Utilizes microbiological data, evidence of
endocardial involvement, and other phenomenon
associated with infective endocarditis to estimate
the probability of infective endocarditis in a given
patient.
Has been shown to be valid and reproducible in
children
Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization
of specific echocardiographic findings. AM J Med 96:200, 1994
Stockheim JA, Chadwick EG, Kessler S, et al. Are the Duke Criteria superior to the Beth Israel
criteria for the diagnosis of infective endocarditis in children? Clin Infect Dis 27:1451, 1998

Duke criteria
Definitive
Pathological criteria
Microorganisms, or
Pathologic lesions
Clinical criteria
2 major criteria, or
1 major and 3 minor criteria, or
5 minor

Possible
Findings consistent with infective endocarditis that fall short of definitive but are not
rejected

Rejected

Firm alternative diagnosis, or

Resolution of manifestations of endocarditis with antibiotic therapy of 4 days or less, or
No pathological evidence of endocarditis at surgery or autopsy with antibiotic therapy of 4
days or less

Duke criteria: Major criteria

Positive blood culture
Typical microorganism consistent with IE, from two separate blood cultures
S. viridans, S. bovis, HACEK
community-acquired S. aureus or enterocci (no primary focus)
Persistently positive cultures
at least two positive cultures, drawn 12 hours apart
all of three, or a majority of four or more cultures (with first and last
sample drawn at least one hour apart

Evidence of endocardial involvement

Positive echocardiogram
oscillating intracardiac mass on valve or supporting structures, or
myocardial abscess, or
new partial dehiscence of prosthetic valve
New valvar regurgitation

The echocardiogram in IE

Duke criteria: Minor criteria

Predisposition
Predisposing heart condition or IV
drug abuser
Fever
> 38.0 C
Vascular phenomena
arterial emboli, septic pulmonary
infarct, mycotic aneurysm,
intracranial hemorrhage, conjunctival
hemorrhage, Janeways lesion
Immunologic phenomena
glomerulonephritis, Oslers nodes,
Roths spots, rheumatoid factors
Microbiologic evidence
positive blood culture but does not
meet major criteria as noted
Echocardiographic evidence
consistent with IE but does not meet
major criteria as noted

Sequelae
Neurologic manifestations, 20%
Cerebral emboli, mycotic aneurysms,
cerebritis, brain abscess, hemorrhage, etc.

Peripheral embolization
Ischemia, infarction, mycotic aneurysms, etc

Pulmonary infarction
Renal insufficiency
Congestive heart failure

Treatment of infective
endocarditis

GENERAL CONSIDERATIONS
Antimicrobial therapy should be
administered in a dose designed to give
sustained bactericidal serum
concentrations throughout much or all of
the dosing interval
In vitro determination of the minimum
inhibitory concentration of the etiologic
cause of the endocarditis should be
performed in all patients

Treatment of infective
endocarditis

GENERAL CONSIDERATIONS
The duration of therapy has to be
sufficient to eradicate microorganisms
growing within the valvular vegetations
The need for prolonged therapy in
treating endocarditis has stimulated
interest in using combination therapy to
treat endocarditis

VIRIDANS STREPTOCOCCI AND STREP. BOVIS

Antibiotic

Dosage and route

Duration Comments

Aqueous crystalline 12-18 million U/24 h 4 wks

preferred in most patients older than 65 yrs
penicillin G sodium IV either continuously
and in those with impairment of the eighth
or in 6 = divided doses
nerve or renal function
or
Ceftriaxone sodium 2g once daily IV or IM
2 wks
Aqueous crystalline
penicillin G sodium
or in six equally
divided doses
with gentamicin
< 1 pg/mL
sulfate

12-18 million U/24 h 2 wks

when obtained 1h after a 20-30 min.
IV either continuously
IV infusion or IM injection, serum
concentration of gentamicin of
approximately 3 mcg/mL is desirable;
1 g IM or IV every 8 h
2 wks
trough concentration should be

Vancomycin
30 mg/kg per 24 h IV 4 wks
vancomycin therapy is recommended for
hydrochloride
in two equally divided
patients allergic to beta lactams; peak
doses, not to exceed 2
serum concentrations of vancomycin should
gram/24h unless serum
be obtained one h after completion of the
levels are monitored
infusion and should be in the range of
30-45 mcg/mL for twice-daily dosing

JAMA 1995; 274:1706

ENTEROCOCCI

STAPH. ENDOCARDITIS IN NATIVE

VALVES

STAPH. ENDOCARDITIS IN PROSTHETIC

VALVES

HACEK ORGANISMS

Indications for surgery in

IE

The indications for surgery in patients with nativevalve IE and prosthetic-valve IE are essentially the
same
Surgery is warranted for patients with active IE who
have one or more of the following complications:
CHF that is directly related to valve dysfunction
Persistent or uncontrolled infection while
receiving appropriate antimicrobial therapy,
including evidence of perivalvular extension
Recurrent emboli, particularly in the presence of
large vegetations

Indications for surgery in

IE

Relative indications for surgery

Evidence of perivalvular infection, such as

intracardiac abscess or fistula formation
Rupture of a sinus of Valsalva aneurysm
Fungal endocarditis
Endocarditis due to highly resistant microorganism
Relapse after a course of adequate antimicrobial
therapy, particularly in prosthetic valve
endocarditis
Culture-negative IE with fever more than 10 days
after starting empirical therapy

Indications for surgery in

prosthetic valve IE

Same as native valve endocarditis

Perivalvular infection
Valve Dehiscence
excessively mobile prosthesis on echo
results in hemodynamic instability

OUTCOME OF
The outcome of
surgery in patients with IE has been
SURGERY
good, particularly when surgical treatment is radical
with the removal of all infected and necrotic tissue
In a recent study of 138 patients who underwent
valve surgery in the presence of active infection, the
early mortality, due to heart failure or septic
multiorgan failure, was 11.5 %
Risk factors for early mortality were NYHA class IV
or cardiogenic shock, advanced age, preoperative
acute renal failure, and staphylococcal infection
Operation for infective endocarditis: Results after implantation of
mechanical valves. Ann Thorac Surg 1998; 65:359.

ACC/AHA recommendation for surgery in patients

with
native valve endocarditis

ACC/AHA recommendation for surgery in

patients with prosthetic valve endocarditis

ACC/AHA recommendation for valve

replacement with mechanical prosthesis

ACC/AHA recommendation for

valve replacement with bioprosthesis

Prevention of IE
No randomized controlled human trials which
definitively establishes the efficacy of antibiotic
prophylaxis.
Most cases of endocarditis are NOT attributable to
an invasive procedure
Current recommendations are based upon literature
analysis of procedure-related endocarditis,
prophylaxis studies in experimental animal models,
and retrospective analysis of human endocarditis
Dajani AS, Taubert KA, Wilson W, et al. Prevention of bacterial endocarditis:
Recommendations by the American Heart Association. JAMA 277;1794: 1997

Endocarditis prophylaxis
recommended
High-risk

Prosthestic cardiac valves

Previous bacterial endocarditis
Complex cyanotic heart disease
Surgically constructed systemic-pulmonary shunts or conduits

Moderate-risk

Most other congenital heart disease

Acquired valvar dysfunction
Hypertrophic cardiomyopathy
Mitral valve prolapse WITH regurgitation and/or thickened
leaflets

Endocarditis prophylaxis NOT

recommended
Isolated secundum ASD
Surgically repaired VSD, ASD, or PDA after 6
months (no residua)
s/p CABG
MVP without MR
Previous Kawasaki disease w/o valvar dysfunction
Previous rheumatic fever w/o valvar dysfunction
Pacemakers and AICDs
Flow murmurs

Dental procedures and IE

prophylaxis: Recommended
Dental extractions
Periodontal procedures
Dental implants and reimplantation of avulsed teeth
Endodontic procedures
Subgingival placement of antibiotic fibers and strips
Initial placement of orthodontic bands (not brackets)
intraligamentary local anesthetic injections
Prophylactic cleaning

Dental procedures and IE

prophylaxis: Not recommended
Restorative dentistry
Non-intraligamentary local anesthetic injections
Taking oral impressions
Fluoride treatments
Oral radiographs
Orthodontic appliance adjustment
Shedding primary teeth

Other procedures and IE

prophylaxis: Recommended
Respiratory
T&A
Surgical procedures involving respiratory mucosa
Rigid bronchoscopy

Gastrointestinal

Sclerotherapy
Esophageal stricture dilation
ERCP with biliary obstruction
Surgery involving biliary tract or intestinal mucosa

Genitourinary tract
Prostatic surgery, cystoscopy
Urethral dilation

Other procedures and IE

prophylaxis: Not Recommended
Respiratory

Endotracheal intubation
PE tubes
Flexible bronchoscopy

Gastrointestinal

Transesophageal echocardiography
Endoscopy (with or without biopsy)

Genitourinary tract

Vaginal hysterectomy, and vaginal or Caesarean deliveries

In uninfected tissues: urethral catheterization, uterine D&C,
therapeutic abortions, sterilization procedures, insertion or
removal of IUDs
Circumcision

How about
Tattoos and Body piercing?
Ear piercing

43% of respondents had ear piercing

Only 6% took antibiotics
23% reported infections but no IE reported

Tattoos
5% of respondents had tattoos
No antibiotics or infections reported

Physicians
Majority of physicians did not approve of piercing or tattoos
60% felt that IE prophylaxis use was appropriate

Cetta F, Graham LC, Lichtenberg RC, Warnes CA. Piercing and tattooing
in patients with congenital heart disease. J Adolesc Health 1999;24:160