Infective Endocarditis

Jason Kollios
Zhi Kai Chua
Sam Craven

1) Extended Match Question (2013 Recall Paper A)

Select from the following list the most LIKELY organism for the given
clinical scenario:
Options:
A.
B.
C.
D.
E.
F.
G.

Aspergillus niger
Escherichia coli
Klebsiella pneumoniae
Enterococcus faecalis
Staphylococcus aureus
Streptococcus mitis
Pseudomonas aeruginosa

A 40 year old man presents with a history of 3 months of night sweats,

lethargy and fatigue. On examination he is febrile, has digital clubbing,
a new mitral regurgitant murmur and haematuria. He is Rheumatoid
factor positive.

2) Question 61 (2013 Recall Paper A)

Most likely long term adverse effect as a result of
the therapeutic regimen for treatment of
enterococcal endocarditis is:
A.
B.
C.
D.
E.

Stevens-Johnson Syndrome
Vestibular dysfunction
Pancytopenia
Renal failure
Alopecia

3) Question 70 (2013 Recall Paper B)

A patient with a mitral valve replacement is about to
attend a gastroscopy with oesophageal dilatation. He
Has no current active GIT infection.
What endocarditis prophylaxis is recommended?
A. None
B. Erythromycin PO 30 min pre-procedure
C. Ciprofloxacin PO 30 min pre-procedure
D. IV ampicillin at time of surgery
E. IV cefazolin at time of surgery

4) Question 17 (2012 Recall Paper A)

For which of the following conditions is antibiotic
prophylaxis for endocarditis most strongly
Indicated during a dental extraction?
A. Mitral valve prolapse
B. Atrial septal defect
C. Aortic stenosis
D. Pulmonary stenosis
E. Prosthetic aortic valve

5) Question 80 (2012 Recall Paper B)

A 50 year old man has a history of anaphylaxis to
cefalexin 20 years ago. He presents now with
Streptococcus viridans endocarditis, which is
Extremely sensitive to penicillin.
What is the best management strategy?
A. Oral penicillin challenge
B. Intradermal penicillin challenge
C. Immediate penicillin desensitisation
D. Meropenem
E. Vancomycin

6) Question 64 (2011 Recall Paper A)

The most common cause of prosthetic valve
endocarditis 12 months after implantation is:
A. HACEK organisms
B. Staphylococcus aureus
C. Streptococcus viridans
D. Coagulase negative staphlycoccus
E. Enterococcus

7) Question 8 (2010 Recall Paper B)

A patient with penicillin hypersensitivity has been in hospital
for one week with aortic valve endocarditis due to S.
aureus which is sensitive for flucloxacillin. He is being treated
with alternative appropriate antibiotics. He suddenly develops
acute pulmonary oedema and a new diastolic murmur. What is
the most appropriate management?

A. Change antibiotics
B. Diuretics
C. Urgent valve replacement
D. Perform rapid penicillin desensitisation and commence
flucloxacillin
E. Admission to ICU with balloon pump insertion

8) Question 50 (2008)
A 56-year-old man with a past history of bicuspid aortic
valve develops bacteraemia with Staphylococcus aureus
and echocardiography shows a 1.0 cm vegetation on the
aortic valve. He has a known history of penicillin
hypersensitivity he reports a sudden onset of tongue and
throat swelling after receiving the drug when he was 20 years
old. What is the most appropriate intravenous antibiotic?
A. Ceftriaxone.
B. Meropenem.
C. Vancomycin.
D. Clindamycin.
E. Flucloxacillin

9) Question 56 (2006)
A 62-year-old man is admitted to hospital with fevers, malaise and myalgias six
weeks after a laparoscopic cholecystectomy. On examination he has a
temperature of 39C, Splinter haemorrhages and a loud pansystolic murmur.
He has a past history of mitral valve prolapse which was diagnosed by
echocardiography. Enterococcus faecalis has been identified in three sets of
blood cultures. The isolate is highly sensitive to penicillin. He has no known
allergies.
The most appropriate therapy is:
A.
B.
C.
D.
E.

ceftriaxone.
vancomycin alone.
ampicillin alone.
ampicillin and gentamicin.
cephalothin and gentamicin.

Epidemiology
Roughly 2-7 cases per 100,000
In-hospital mortality 15-20%
Males > Females
More common in age > 65
Up to 1/3 health care-associated
16-30% involve prosthetic valves
80-90% L-sided endocarditis (mitral, aortic)
50% cases occur in patients with no history of valve disease

Risk Factors
Structural heart disease
Valvular (e.g. rheumatic heart disease, MVP)
Congenital heart disease

Prosthetic valves
History of infective endocarditis
Intravascular/cardiac device
Intravenous drug use
Haemodialysis
HIV

Pathogenesis

Table taken from Antimicrobial Chemotherapy, 5th Edn, Greenwood, Finch, Davey and Wilcox

Pathogenesis
Endothelial injury

High-pressure jets from turbulent blood flow

Provocations from foreign bodies, eg. catheters, electrodes
Chronic inflammation
Valvular degeneration

Non-bacterial thrombotic endocarditis (NBTE)

Platelets and fibrin deposit on damaged endothelium

Bacteraemia
Dental abscess, infected skin lesion, or vascular catheter
Adherence of bacteria to NBTE
S. aureus can adhere directly to intact endothelium

Bacterial multiplication and development of vegetation

Further bacterial growth in cells and matrix evades host immune
responses (difficult eradication)

Acute vs Subacute
Acute

Develops abruptly and progresses rapidly

Source of infection usually evident
Can affect normal valves
e.g. S. aureus, beta-haemolytic Strep, pneumococci

Subacute
Develops insidiously and progresses slowly
Often affects abnormal/damaged valves
Slow if any cardiac structure damage, rarely metastasizes, gradually
progressive
e.g. Streptococcus, enterococcus, S. aureus, CoNS, HACEK

Prosthetic valve endocarditis

Early < 2 months
Usually nosocomial
Staph aureus, CoNS

Late > 12 months

Similar to native valve endocarditis
Streptococci, Staph aureus

Symptoms
Fever (80-90%)
Chills, sweats (40-75%)
Anorexia, malaise, weight loss (25-50%)
Myalgias, arthralgias (15-30%)
Back pain (7-15%)
Other depending on site of septic embolisation

Signs

Fever (80-90%)
New murmur (80-85%)
Worsening of known murmur (20-50%)
Arterial emboli (20-50%)
Splenomegaly (15-50%)
Clubbing (10-20%)
Neurological manifestations (20-40%)
Petechiae (10-40%)
Splinter haemorrhages (8%)
Janeways lesions (5%)
Roths spots (5%)
Oslers nodes (5%)
Conjunctival haemorrhage (5%)

Organisms
Depends on:

Native vs prosthetic
Source of infection
Host factors
Timeframe

Streptococci and staphylococci > 80%

S. aureus most common in IVDUs and tricuspid IE
S. epidermidis (CoNS) most common in early prosthetic valve IE <
2 months
Streptococcus most common in late prosthetic valve IE >12
months
Other causative organisms of IE:
Enterococci, Strep bovis, HACEK, non-HACEK GNB, Candida spp

Bacteria
S. mutans
S. bovis
S. sanguis
S. mitior
Enterococcus
S. angiosus/milleri
Group G strep
Group B strep
Group A strep

Endocarditis: Non-endocarditis
14:1
6:1
3:1
2:1
1:1.2
1:3
1:3
1:7
1:32

Table taken from 2014 FRACP Endocarditis lecture, adapted from Mandell, Douglas and Bennett

Infective Endocarditis Review NEJM, April 11, 2013

Typical Source Organisms

Oral cavity, skin, upper respiratory tract
Viridans streptococci, staphylococci
HACEK organisms

Gastrointestinal
Strep bovis (gallolyticus) (associated with GI cancers)

Genitourinary
Enterococci

Prophylaxis
High Risk Patients
prosthetic cardiac valve or prosthetic material used for cardiac
valve repair
previous infective endocarditis
congenital heart disease but only if it involves:
unrepaired cyanotic defects, including palliative shunts and conduits
completely repaired defects with prosthetic material or devices during
the first 6 months after the procedure (after which the prosthetic
material is likely to have been endothelialised)
repaired defects with residual defects at or adjacent to the site of a
prosthetic patch or device (which inhibit endothelialisation)

rheumatic heart disease in high-risk patients

eTG Antibiotic Guidelines, version 15, 2015

Prophylaxis
High Risk Procedures
Dental

Extraction
Periodontal surgery
Replanting avulsed teeth
(there is a group of procedures where it may be considered)

Respiratory
Invasive procedure to treat an abscess
Tonsillectomy/adenoidectomy

Gastrointestinal
Established genitourinary/GI infection, ensure enterococcus cover

Note- not needed for colonoscopy, gastroscopy or bronchoscopy

+/- biopsy
(UK now does not recommend prophylaxis in any circumstance)
eTG Antibiotic Guidelines, version 15, 2015

Diagnosis
Clinical Suspicion
Clinical context with risk factors
Microbiological Evidence
Draw blood cultures
If three sets of cultures are taken prior to Abx, around 90% of
organisms are identified

Other cultures if available

Echocardiographic Evidence
TTE vs TOE

Diagnosis- Modified Duke Criteria

Pathological Criteria
Microorganism demonstrated by culture or histological examination
of a vegetation or an embolised vegetation or intracardiac abscess

Clinical Criteria
Two major OR One major and three minor OR five minor
Major
Positive blood culture for IE
Typical organisms- Viridans strep, Staph aureus, HACEK, enterococci
Persistently positive blood cultures more than 12hrs apart
Single positive culture or serology for Coxiella burnetii

Evidence of endocardial involvement

Positive TTE (strict criteria)
New valvular regurgitation

Minor

Predisposition- valvular heart disease or IVDU

Fever > 38.0oC
Vascular phenomena- arterial emboli, septic infarcts, mycotic aneurysm
Immunologic phenomena- GN, Oslers nodes, Roth spots
Microbiological evidence not meeting major criteria

Treatment
Many specific regimes
Some have been asked about in the RACP exam
Difficulty with therapy
Vegetations avascular, encased in fibrin
Need high dose antibiotics to penetrate vegetation
Need longer treatment time to prevent relapse

Empiric therapy (Native valve)

Gentamicin PLUS Benpen PLUS Flucloxacillin

Empiric therapy (Prosthetic valve)

Gentamicin PLUS Vancomycin PLUS Flucloxacillin
eTG Antibiotic Guidelines, version 15, 2015

Treatment
Staphylococcal endocarditis
If MSSA- Flucloxacillin for 4-6 weeks
If MRSA- Vancomycin for 4-6 weeks

HACEK endocarditis
Ceftriaxone for 4-6 weeks

eTG Antibiotic Guidelines, version 15, 2015

Treatment
Viridans streptococci endocarditis
Uncomplicated
Benzylpenicillin PLUS Gentamicin for 2 weeks
OR Benzylpenicillin alone for 4 weeks

Complicated
Benzylpenicillin (4 weeks) PLUS Gentamicin for 2 weeks

Enterococcal endocarditis
Intrinsically more resistant, so even if susceptible to penicillins
needs the addition of gentamicin
Gentamicin (4-6 weeks)
PLUS EITHER

Benpen OR Amoxycillin (4-6 weeks)

eTG Antibiotic Guidelines, version 15, 2015

Treatment
Why gentamicin with streptococci and enterococci?
Gentamicin alone has little activity against streptococci

They act in synergy

Beta-lactams inhibit peptidoglycan cross-links within the
bacteria cell wall- disrupting its formation and triggers
digestion of the existing cell wall
Aminoglycosides are then able to more readily penetrate the
cell wall and enter the cell, disrupting protein synthesis

Treatment
Penicillin Hypersensitivity
Two Strategies
1) Desensitisation

Renders mast cells unresponsive to the drug resulting in temporary tolerance.

Effective as long as the patient is receiving the drug
Sensitivity returns soon after the drug is cleared from the body.
Contraindicated in previous DRESS or SJS/TEN
Usually done as an inpatient

2) Alternative antibiotics
Will depend on bacteria cultures and sensitivities.

Complications
Heart Failure
Can happen acutely or subacutely
Most common cause of death in IE
Aortic valve most at risk

Perivalvular Abscess
Most common at the aortic valve and annulus
Can extend into conducting tissues, causing heart block

Complications
Septic Embolisation

Pulmonary emboli (right sided)

Splenic or renal infarcts
Stroke
Ischaemia of extremities
Spinal cord infarction
Metastatic abscess formation
Mycotic aneurysm
Secondary seeding- joints, bones, muscles

Complications
Related to therapy

Aminoglycoside induced ototoxicity or nephrotoxicity

Drug allergies
Line related infected
Line related thrombosis
DVT

Indications for Surgery

1) Heart Failure
2) Uncontrolled Infection
3) Prevention of embolism

ACC/AHA 2006 Guidelines

American Heart Association/American College Cardiology
Class I

Heart failure due to stenosis or regurgitation

AR or MR with increased LVED or LA pressure, or Pulm HTN
Fungal infection, or other highly resistant organisms
Locally advanced disease- CHB, fistula, abscess

Class IIa
Failure of medical management- recurrent emboli or new
vegetations

Class IIb
Prevention of emboli if mobile vegetation >10mm

Infective Endocarditis Review NEJM, April 11, 2013

Back to the Questions

Answers
1.
2.
3.
4.
5.
6.
7.
8.
9.

F
B
A
E
C
C
C
C
D

Thank You