Infective Endocarditis

Definition
◼ Endovascular microbial infection of cardiovascular
structures, including endarteritis of large
intrathoracic vessels or intracardiac foreign bodies
facing the bloodstream
◼ Native valve, atrium/ventricle endocardium
◼ PDA, arterio-venous shunt, coarctation aorta

◼ Conduit, prosthetic valve, pacemaker

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

INFECTIVE ENDOCARDITIS
◼ characterized by inflammation or infection

◼ two major predisposing factors:

◼ susceptible cardiac or vascular substrate
◼ lesions associated with high-velocity flow, jet impact and focal
increases in the rate of shear
◼ source of bacteremia
 PATIENTS AT RISK
◼ acquired valvular heart disease
◼ rheumatic heart disease
◼ degenerative conditions
◼ mitral valve prolapse with valve leakage
◼ congenital heart diseases
◼ hypertrophic cardiomyopathy
◼ after cardiac surgery with
◼ prosthetic valves
◼ constructed systemic or pulmonary conduits
◼ previous history of IE

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

Proposed scheme for the pathogenesis of infective endocarditis

Mandell, Bennett, & Dolin:

Principles and Practice of Infectious Diseases, 6th ed
PATHOGENESIS OF INFECTIVE ENDOCARDITIS

Traumatized Non Bacterial Bacteremia Bacterial Fibrin

endothelium Thrombotic Endocarditis Deposition
Endocarditis
+
Platelet
+
Fibrin

Embolization Layering
 Classification
◼ Old clasiffication: acute/subacute/chronic
◼ Present classification, based on:
◼ Activity and recurrence
◼ Diagnostic status

◼ Pathogenesis

◼ Anatomical site

◼ Microbiology

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

 Classification based on
Activity and recurrence
◼ Activity related to surgery
◼ Active IE : if diagnosis of IE  2 months
before surgery
◼ Recurrent IE: IE develops after had been
eradicated
◼ Persistent IE: IE has never been eradicated

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

 Classification based on Diagnosis
◼ Established IE: clinically and involvement of
endocardium is established
◼ Suspected IE: clinical strongly suspected, but no
evidence of endocardium involvement
◼ Possible IE: potential differential diagnosis

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

 Classification based on Pathogenesis

◼ Native valve endocarditis (NVE)

◼ Prosthetic valve endocarditis (PVE)
◼ Early PVE (<1 year since surgery)
◼ Late PVE (>1 year since surgery)

◼ IE in iv drug abuse (IE in IVDA)

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

 Classification based on
Anatomic location
◼ Right side IE
◼ Left side IE
◼ Specific anatomical site (mitral, aortic, mural,
etc)

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

 Classification based on Microbiology

◼ Culture, serological test, histological and/or

molecular biology (PCR)
◼ Culture negative, serological negative,
histological negative, and/or PCR negative
◼ If all negative → microbiologically negative

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

DIAGNOSIS
 Diagnosis
◼ Modified Duke Criteria
◼ Based on
◼ pathological (surgery/autopsy)
◼ Microbiological

◼ Echocardiography

◼ Clinical
 Definition of IE According to Modified Duke Criteria

Definite IE

Pathological criteria
◼ Microorganisms: demonstrated by culture or histology in
a vegetation, or in an intracardiac abscess, or
◼ Pathological lesions: vegetation or intracardiac abscess
confirmed by histology

Clinical criteria
◼ 2 major criteria, or
◼ 1 major and 3 minor criteria, or
◼ 5 minor criteria

AHA guidelines IE. Circulation 2005;111;e394-e433

Possible IE
Findings consistent with IE that fall short of “Definite” but
not “Rejected”

1 major criterion and 1 minor criterion; or

3 minor criteria

Rejected
• Firm alternate diagnosis for IE, or
• Resolution of manifestations of IE with antibiotic therapy
for < 4 days, or
• No pathological evidence of IE at surgery or autopsy,
after antibiotic therapy for <4 days
• Does not meet criteria for possible IE as above

AHA guidelines IE. Circulation 2005;111;e394-e433

◼ Major criteria

1. Positive blood culture for IE

A. Typical microorganism consistent with IE from 2 separate blood cultures
as noted below:
(i) viridans streptococci,* Streptococcus bovis, or HACEK group,
(ii) Staphylococcus aureus or community-acquired enterococci,
in the absence of a primary focus

B. Microorganisms consistent with IE from persistently positive blood

cultures defined as
(i) At least 2 positive cultures of blood samples drawn >12
hours apart
(ii) all of 3 or a majority of ≥ 4 separate cultures of blood (with
first and last sample drawn at least 1 hour apart)

Single positive blood culture for Coxiella burnetti or anti-phase1 IgG

antibody titer > 1:800
AHA guidelines IE. Circulation 2005;111;e394-e433
2. Evidence of endocardial involvement
A. Positive echocardiogram for IE
(i) 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
(ii) abscess, or
(iii) new partial dehiscence of prosthetic valve, or

B. New valvular regurgitation (worsening or changing of preexisting

murmur not sufficient)

TEE recommended for patient with

◼ prosthetic valves;
◼ at least possible IE by clinical criteria, or
◼ complicated IE
◼ Minor criteria

1. Predisposition: predisposing heart condition or intravenous drug

use
2. Fever: temperature >38.0°C
3. Vascular phenomena: major arterial emboli, septic pulmonary
infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival
hemorrhages, and Janeway lesions
4. Immunologic phenomena: glomerulonephritis, Osler’s nodes,
Roth spots, and rheumatoid factor
5. 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
6. Echocardiographic findings: consistent with IE but do not meet
a major criterion as noted above
 CLINICAL FEATURES of IE in GENERAL POPULATION & in SPECIFIC AT-RISK GROUPS
No. of episodes (% of total)
Clinical features Intravenous drug Prosthetic valve
Native valve
abusers Early Late
Symptoms
Fever 170 (75) 42 (87) 7 (77) 47 (78)
Chills 104 (46) 35 (73) 5 (55) 32 (53)
Arthralgias/myalgias 44 (19) 13 (27) - 10 (17)
Back pain 22 (10) 5 (10) - 2 (2)
Pleuritic chest pain 10 (4) 17 (45) - 3 (5)
Clinical signs
Cardiac murmur 196 (86) 45 (93) 8 (88) 58 (96)
Petechia, emboli 80 (35) 3 (6) 3 (33) 30 (50)
Osler nodes, Janeway lesions, Roth spots 26 (11) 3 (6) 0 (0) 6 (10)
Splinter hemorrhages * 28/80 (35) 3/15 (30) 5/7 (71) 17/33 (51)
Palpable spleen * 15/80 (19) 3/15 (30) 2/7 (28) 2/33 (6)
Central nervous system manifestations † 38/148 (25) 4/33 (12) 0/2 (0) 5/27 (18)
Renal insufficiency † 45/148 (30) 5/33 (15) 1/2 (50) 8/27 (30)
Temperature (°F (°C))
<100.4 (<37.8) 64 (28) 15 (31) 3 (34) 21 (35)
100.4–102 (37.8–38.9) 82 (36) 12 (25) 6 (66) 22 (37)
>102.2 (>39) 81 (36) 21 (44) 0 (0) 17 (28)
Total episodes 228 48 9 60
Embolic skin lesions (Janeway spots) in mitral valve endocarditis
caused by Staphylococcus aureus

Mandell, Bennett, & Dolin: Principles and Practice of Infectious Diseases, 6th ed. 2005
 Conjungtival petechiae Splinter hemorrhages

Braunwald E [ed]: Heart Disease. 4th ed. Philadelphia, WB Saunders, 1992, p 1087
Kaye D: Infective Endocarditis. Baltimore, University Park Press, 1976
Osler Node

Cohen & Powderly: Infectious Diseases, 2nd ed

Roth spot

University of Michigan
Diagnostic: Janeway Lesions
Diagnostic: Splinter Hemorrhage
Diagnostic: Osler’s Nodes
Diagnostic: Roth’s Spots
Parasternal long-axis view of patient with aortic valve vegetation

Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed

Use of Echo during diagnosis & treatment of IE

◼ Early
◼ ASAP (<12 h after initial evaluation)
◼ TEE preferred. (TTE if TEE is not available)

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

 Evaluation of infective endocarditis
Suspected
Endocarditis

Ancillary laboratory Transthoracic Blood culture x3

tests Echocardiogram

Nondiagnostic Diagnostic

Transesophageal Diagnostic
Echocardiogram

Negative

Diagnosis unlikely Ferri's Clinical Advisor 2007: Instant Diagnosis and Treatment, 9th ed. 2007
 Blood culture

◼ In prospective series of IE, positive cultures were

significantly higher in venous blood culture than
arterial blood
◼ No correlation between body temperature and
positive blood culture → for diagnosing IE, can
draw blood sample at anytime (not only during
fever)

ESC Guidelines of IE. EHJ 2004; 25: 267 – 276

COMPLICATIONS
 Embolic events
◼ Most common & predictor of death
◼ Higher prevalence in cerebral than peripheral
◼ Increased risk of emboli in:
◼ Infection of staphylococci, enterococci, HACEK,
fungi
◼ Vegetation: 10 mm, mobile, low density, rapid
growth
◼ IE in Mitral valve

◼ Early course of IE
 Cardiac failure
◼ Acute regurgitation, myocarditis
◼ Has greatest impact in prognosis
◼ Acute aortic regurgitation has worse clinical
tolerance than mitral & tricuspid
◼ Should undergo surgery. Delay should be
discouraged.
◼ Poor outcome for surgery, but better than
medical therapy alone
 Acute renal failure
◼ Due to
◼ Immune complex glomerulonephritis
◼ Hemodynamic instability

◼ Renal infarct / emboli

◼ Drug toxicity

◼ Treatment depends on clinical

◼ Usually reversible
 Periannular extension of infection

◼ Can manifest as
◼ Perivalvular abscess (usually in PVE)
◼ Arrhytmia or conduction disturbance (aortic NVE)

◼ Fistula, pseudoaneurysm

◼ Obstructive lesion

Predict death, CHF and need of surgery

 Mycotic aneurysm
◼ Uncommon
◼ Result from septic embolization of vegetations
to arterial vasa vasorum or intraluminal space
◼ Intracranial MA is more frequent than
extracranial MA (visceral and extremities)
Antimicrobial Therapy and Surgery
 Antimicrobial Therapy

◼ If initiation of antimicrobial therapy is urgent, empiric

antibiotic treatment can be started thereafter (blood
culture)
◼ In all other cases it is recommended to post-pone
therapy until blood cultures become positive.
◼ Previous short term antibiotic → discontinue for at
least 3 day before taking blood cultures.
◼ Previous long term antibiotic treatment → discontinue
for 6 - 7 days.

ESC guideline; European Heart J 2004

Therapy of NVE Caused by Highly Penicillin-Susceptible
Viridans Group Streptococci and Streptococcus bovis

AHA guidelines IE.

Circulation 2005;111
◼ 2 week regimen (combination) has similar cure
rates to 4 week regimen
◼ 4 week regimen (monotherapy) preferred in
◼ patients >65 yo
◼ with 8th cranial nerve impairment
◼ renal dysfunction
◼ Cardiac/extracardiac abscess

◼ Vancomycin only for patients not tolerate to

penicillin / ceftriaxone
◼ For combination antibiotics → given at same
time or close together to increase synergistic
effect
Therapy of NVE by Viridans Group Streptococci and Streptococcus bovis
Relatively Resistant to Penicillin

AHA guidelines IE. Circulation 2005;111;e394-e433

◼ Patients with endocarditis caused by penicillin-
resistant (MIC 0.5 g/mL) strains should be
treated with regimen for enterococcal
endocarditis
Therapy for NVE / PVE by Enterococcal Susceptible to
Penicillin, Gentamicin, and Vancomycin
Therapy for NVE / PVE by Enterococcal Susceptible to Penicillin
and Vancomycin, but resistant to gentamicin
Therapy for NVE / PVE by Enterococcal Resistant to Penicillin,
Gentamicin, and Vancomycin

◼ All regimens in  8 weeks

◼ E faecium
◼ Linezolid 1200 mg/24 h iv or po in 2 divided doses, or
◼ Quinupristin –dalfopristin 22.5 mg/kg/24 h iv in 3 divided doses
◼ E faecalis
◼ Imipenem / cilastatin 2 g/24 h iv in 4 divided doses
PLUS
◼ Ampicillin sodium 12 g/24 h iv in 6 divided doses

OR
Ceftriaxone sodium 2 g/24 h iv/im in 1 dose
PLUS
◼ Ampicillin sodium 12 g/24 h iv in 6 divided doses
Therapy for Endocarditis of Prosthetic Valves or Other Prosthetic Material
by Viridans Group Streptococci & Streptococcus bovis

Highly Penicillin-Susceptible

AHA guidelines IE. Circulation 2005;111;e394-e433

Therapy for Endocarditis NVE Caused by Staphylococci

Oxacillin
susceptible strains
Oxacillin resistant strains
Therapy for Both NVE & PVE Caused by HACEK Microorganisms
 Culture negative Endocarditis
◼ Up to 20% of IE patients
◼ Result from
◼ Inadequate microbiological techniques
◼ Highly fastidious (slow growing) bacteria or
nonbacterial pathogens
◼ Previous administration of antimicrobial agents
before blood cultures were obtained
◼ If negative culture due to previous antibiotics
◼ Native valve endocarditis
◼ For acute presentation → should cover S aureus
◼ For subacute → cover S aureus, viridans group
streptococci, & enterococci
◼ Prosthetic valve endocarditis
◼ < 2 mo after surgery → aerobic Gram-negative bacilli
◼ < 1 year → Oxacillin resistant staphylococci

◼ > 1 year → Oxacillin sensitive staphylococci, viridans

group streptococci, enterococci
◼ If negative culture due to uncommon / rare
endocarditis pathogens
◼ Bartonella species
◼ Coxiella burnetii Most Common
◼ Brucella species

◼ Chlamydia species

◼ Legionella species

◼ Tropheryma

◼ whippleii

◼ Fungi
 IE in Intravenous Drug User (IVDU)
◼ Most common: S aureus *, **
◼ MRSA had been emerging (60-70% in Europe)**
◼ Other organisms: P aeruginosa, Candida,
enterococci, streptococci *, **
◼ Polymicrobial infection 5-10% **

* AHA guidelines IE. Circulation 2005;111;e394-e433

** ESC guidelines Infective Endocarditis 2004

 Antibiotic in IVDU
◼ Depend on
◼ Suspected microorganism
◼ Type of drug and solvent used
◼ Side of the heart involved
◼ S aureus must always be covered
◼ In pentazocine addicts → add anti pseudomonas
◼ IVDU with underlying valve lesion and/or left side
involvement → add anti streptococci & enterococci
 Antibiotic Prophylaxis
◼ Background for prophylaxis:
◼ Bacteremia causes endocarditis
◼ Viridans group streptococci are part of normal oral flora, and
enterococci are part of normal GI and GU tract flora
◼ These microorganisms were usually susceptible to antibiotics
recommended for prophylaxis
◼ Antibiotic prophylaxis prevents viridans group streptococcal or
enterococcal experimental endocarditis in animals
◼ Large number of poorly documented case reports implicated a
dental procedure as a cause of IE
◼ In some cases, there was a temporal relationship between a
dental procedure and the onset of symptoms of IE
◼ The risk of significant adverse reactions to an antibiotic is low
in an individual patient
◼ Morbidity and mortality from IE are high.
AHA guideline: Prevention of Infective Endocarditis. Circulation 2007;115
◼ No published data accurately determine the
absolute risk of IE results from dental procedure
◼ Estimation:
◼ Normal population: 1 case of IE per 14 million dental
procedures
◼ MVP: 1 per 1.1 million dental procedures

◼ CHD: 1 per 475 000

◼ RHD: 1 per 142 000

◼ Prosthetic cardiac valve: 1 per 114 000

◼ Previous IE: 1 per 95 000

AHA guideline: Prevention of Infective Endocarditis. Circulation 2007;115

 Cardiac conditions with highest risk of adverse
outcome from endocarditis for which prophylaxis
is recommended
◼ Prosthetic cardiac valve
◼ Previous IE
◼ Cardiac transplantation
◼ Congenital Heart Disease (CHD)
◼ Unrepaired cyanotic CHD, including palliative shunt & conduit
◼ Completely repaired CHD with prosthetic material/device
during first 6 months after procedure
◼ Repaired CHD with residual defects of prosthetic patch/device

Antibiotic prophylaxis should be limited to conditions above, and not based

solely on an increased lifetime risk of acquisition of IE

AHA guideline: Prevention of Infective Endocarditis. Circulation 2007;115

Regimens in Dental Procedure for IE prophylaxis
Regimen:
Situation Agent Single Dose 30 to 60 minute
Before Procedure
Adults Children

Oral Amoxicillin 2g 50 mg/kg

Unable to take oral Ampicillin or 2 g IM or IV 50 mg/kg IM or IV
medicine Cefazolin or Ceftriaxone 1 g IM or IV 50 mg/kg IM or IV
Allergic to Penicillin Cephalexin*† or 2g 50 mg/kg
or Ampicillin ⎯ oral Clindamycin or 600 mg 20 mg/kg
Azithromycin or 500 mg 15 mg/kg
Clarithromycin
Allergic to Penicillin Cefazolin or Ceftriaxone† 1 g IM or IV 50 mg/kg IM or IV
or Ampicillin and or 600 mg IM or IV 20 mg/kg IM or IV
unable to take oral Clindamycin
medicine

19
AHA guideline: Prevention of Infective Endocarditis. Circulation 2007;115
 Regimens in Respiratory Procedure

◼ No published data conclusively demonstrate a

link between these procedures and IE
◼ Only in patients with high risk of adverse
outcome who perform incision or biopsy (not
bronchoscopy) → Similar regimens to dental
procedure
◼ If invasive respiratory tract procedure to treat an
established infection by S aureus → use agent for
S aureus (Vancomycin if MRSA)

AHA guideline: Prevention of Infective Endocarditis. Circulation 2007;115

 Regimens in GI/GU Procedure

◼ No studies demonstrate that administration of

antimicrobial prophylaxis prevents IE in
association with procedures on GI or GU tract
◼ Only in patients with high risk of adverse
outcome who have GI/GU infections → use
agent for enterococci

AHA guideline: Prevention of Infective Endocarditis. Circulation 2007;115

 New from AHA for IE prophylaxis
◼ Bacteremia from daily activities (chewing food, tooth
brushing and flossing, use of wooden toothpicks, use
of water irrigation devices) is much more likely to cause
IE than a dental procedure
◼ Extremely small number of IE might be prevented by
antibiotic prophylaxis, even if prophylaxis is 100%
effective
◼ Limit prophylaxis only to conditions with high adverse
outcome from endocarditis
◼ Maintenance of optimal oral health and hygiene may
reduce the incidence of bacteremia from daily activities
and is more important than prophylactic antibiotics
AHA guideline: Prevention of Infective Endocarditis. Circulation 2007;115
 In NVE, Surgery should be considered
◼ Acute aortic or mitral regurgitation and CHF
◼ Evidence of perivalvular extension
◼ Persistent infection after 7-10 days of adequate antibiotic
◼ Infection due to microorganisms with poor response to
antibiotic
◼ (Fungi, Brucella, Coxiella, S lugdunensis, enterococcus with
resistance to gentamycin, gram negative organisms)
◼ Mobile vegetation of >10 mm before or during first
week of antibiotic
◼ Recurrent emboli despite antibiotic therapy
◼ Obstructive vegetation
Eur Heart J 2004;25 (2):267-76
 Surgery in PVE
◼ Early PVE
◼ Late PVE with complication, particularly if
staphylococci are the infecting organism
Surgery
Echocardiographic features suggesting potential need for surgery