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. Aspergillus niger

B. Escherichia coli

C. Klebsiella pneumoniae

D. Enterococcus faecalis

E. Staphylococcus aureus

F. Streptococcus mitis

G. 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. Stevens-Johnson Syndrome

B. Vestibular dysfunction

C. Pancytopenia

D. Renal failure

E. 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. ceftriaxone.

B. vancomycin alone.

C. ampicillin alone.

D. ampicillin and gentamicin.

E. 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

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

Pathogenesis

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

Early < 2 months

Usually nosocomial

Staph aureus, CoNS

Late > 12 months

Similar to native valve endocarditis

Streptococci, Staph aureus

Prosthetic valve endocarditis

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 Endocarditis: Non-endocarditis

S. mutans 14:1

S. bovis 6:1

S. sanguis 3:1

S. mitior 2:1

Enterococcus 1:1.2

S. angiosus/milleri 1:3

Group G strep 1:3

Group B strep 1:7

Group A strep 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

Answers

1. F

2. B

3. A

4. E

5. C

6. C

7. C

8. C

9. D

Back to the Questions

Thank You