Infective Endocarditis

Definition
Infective endocarditis is an
infection that affects some part
of the endocardium
The endocardium is the tissue
that lines the inside of the heart
chambers.

The infection usually involves

one or more heart valves which
are part of the endocardium.
It is a serious infection that is
life-threatening.
Easily overlooked or
misdiagnosed and clinicians
should be vigilant and well versed
in the manifestations to avoid
missing the diagnosis

Epidemiology/Aetiology
The incidence is approx. 1.7-6.2 per 100,000 patient years, rates higher with at
risk cohorts
Incidence has remained constant for 50 years

Risk Factors:
Cardiac conditions
Valvular heart disease with stenosis or regurgitation
Valve replacement
Intracardiac devices (pacemaker wires)
Structural congenital heart disease, including surgically corrected or palliated conditions
Excluding:

Isolated atrial septal defect

Fully repaired ventricular septal defect
Fully repaired patent ductus arteriosus
Closure devices that are judged to be endothelialised

Previous IE
Hypertrophic cardiomyopathy

Other
Recreational drug abuse
Invasive vascular procedures
Haemodialysis
Coexisting conditions that suppress immunity (DM, HIV/AIDs)

Pathogenesis
All cases have nonbacterial thrombotic endocarditis (sterile fibrin-platelet vegetation) as prerequisite
for adhesion and invasion
Site of thrombus is influenced by the Venturi effect, with deposition on low pressure side

Historical divide into acute and sub-acute, classifying the rate of progression and severity of disease
Sub-acute bacterial endocarditis (SBE) often due to streptococci of low virulence and mild to moderate
illness which progresses slowly over weeks and months, and has low propensity to haematogenously seed
extracardiac sites
Acute bacterial endocarditis (ABE) is a fulminant illness over days to weeks, and is more likely due to
staphylococcus aureus, which has much greater virulence, or disease-producing capacity and frequently causes
metastatic infection

Classification now discourage because the associations arent strong enough to be relied upon
clinically. The terms short incubation (<6 weeks) and long incubation (>6 weeks are preferred)
Valves most commonly affected (in decreasing order of frequency):
Mitral valve
Aortic valve
Combined mitral and aortic
Tricuspid valve
Pulmonary valve rare

Complications

MI
Pericarditis
Cardiac arrhythmias
Heart valve insufficiency
Heart failure
Arterial emboli, infarctions, mycotic aneurysms
Arthritis, myositis
Glomerulonephritis, acute kidney disease
Stroke syndromes
Mesenteric or splenic abscess or infarction

Organisms responsible
Staphylococcus aureus
Most common cause of IE
Most common with prosthetic valves, acute IE and IE related to IV drug abuse
High mortality rate
Coagulase negative S. aureus causes sub-acute disease similar to Streptococcus viridans,
accounting for 30% of IE associated with prosthetic valves

Streptococci (Oral and Group D)

S. viridans: 50-60% of sub-acute IE cases
Group D streptococci: Third most common cause, usually sub-acute
Streptococcus intermedius: 15% of all cases
Group A, C and G: Acute IE similar with S. aureus. High mortality up to 70%
Group B: Acute disease, high mortality requiring valve replacement; Occurs in pregnancy
and the elderly

Pseudomonas aeruginosa
Usually acute IE and requires surgery for cure

HACEK organisms (Haemophilus spp., Aggregatibacter actinomycetemcomitans,

Cardiobacterium spp., Eikenella corrodens, Kingella kingae)
Usually sub-acute disease and about 5% of all IE.

Fungi:
Candida, chlamydia; Causes sub-acute disease.

Enterococci.

Presentation
Variable, requires high index of suspicion and low threshold for
investigation
May present as acute, rapidly progressive infection, or sub-acute/chronic
disease with nonspecific symptoms e.g. fatigue, low-grade fever, flu-like
illness, polymyalgia-like symptoms, loss of appetite, back pain, pleuritic
pain, abdo symptoms
Majority of patients present with fever, associated with chills, poor
appetite and weight loss
Heart murmurs found in up to 85% and recently reported in 48% of
patients
Immunological phenomena, such as splinter haemorrhages, Roth's spots
and glomerulonephritis, are now less common, but emboli to brain
(cerebrovascular accident), lung or spleen occur in 30% of patients and
are often the presenting feature.
Atypical presentation (no fever) more common in the elderly
Should be considered when patients presents with stroke/TIA and fever

Examination
Fever
Elderly and chronically ill may
not present

Heart murmurs
Most patients have one,
exception is right sided IE
where only 1in3 have a
murmur
Most common is aortic
regurgitation
S1 is soft and there is an early
diastolic murmur, best heard in
the aortic area, with the patient
sitting forward and in expiration.

Petechiae

Conjuctivae
Hands and feet
Chest and abdo wall
Oral mucosae and soft palate

 Splinter or subungual
haemorrhages
Oslers nodes
Small tender red-to-purple
nodules on the pulp of the
terminal phalanges of the
fingers and toes

Janeways lesions
Irregular painless erythematous
macules on the thenar and
hypothenar eminence (usually
with acute IE and S. aureus).

Clubbing
Roths spots
Retinal hemorrhages with white
or pale centers

Arthritis
Splenomegaly
Meningism/meningitis

Investigations
Blood cultures
Do 3 sets at different times from different sites at peak of fever.
8590% are diagnosed from the 1st 2 sets
10% are culture-negative

Blood tests
Normochromic, normocytic anaemia, neutrophilia, high ESR/CRP.
Also check U&E, Mg2+, LFTs

Urinalysis: Microscopic haematuria

CXR: Cardiomegaly
Echocardiography
Transthoracic echocardiography (TTE) is the initial investigation of
choice.
In cases with an initially negative TTE/transoesophageal
echocardiography (TOE) examination, repeat TTE/TOE should be
performed 7-10 days later if the clinical suspicion of IE remains high

Diagnostic Criteria
Definite infective endocarditis
Pathological criteria positive OR
Two major criteria OR
One major and two minor criteria OR
Five minor criteria
Pathological criteria
Positive histology or microbiology of
pathological material obtained at autopsy
or cardiac surgery (valve tissue,
vegetations, embolic fragments, or
intracardiac abscess content)
Major criteria
Two positive blood cultures showing typical
organisms consistent with infective
endocarditis, such as Streptococcus
viridansand the HACEK group OR
Persistent bacteraemia from two blood
cultures taken > 12 hours apart or three or
more positive blood cultures where the
pathogen is less specific, such
asStaphylococcus aureusandStaph
epidermidisOR

Positive serology forCoxiella burnetti,

Bartonellaspecies, orChlamydia
psittaciOR
Positive molecular assays for specific gene
targets
Positive echocardiogram showing
oscillating structures, abscess formation,
new valvular regurgitation, or dehiscence
of prosthetic valves
Minor criteria
Predisposing heart disease
Fever > 38C
Immunological phenomena such as
glomerulonephritis, Osler's nodes, Roth
spots, or positive rheumatoid factor
Microbiological evidence not fitting major
criteria
Elevated C reactive protein or erythrocyte
sedimentation rate
Vascular phenomena such as major emboli,
splenomegaly, clubbing, splinter
haemorrhages, petechiae, or purpura

Management
NICE: Prophylaxis not recommended. Bacteraemia happens constantly, so
giving antibiotics routinely after dental surgery is unnecessary.
Have a high index of suspicion -> admit to hospital with suspected IE for full
investigation; cardiologist and infection specialist should be closely involved
European Heart Journal:
Antimicrobial therapy
Oral therapy has been used but rarely advocated due to concerns about efficacy
IV is recommended to ensure adequate dosing and administration
Sometimes oral therapy has to be used as safest treatment
Use agents with similar oral/IV bioavailability
Ciprofloxacin, linezolid and rifampicin have excellent oral bioavailability.

Home therapy if stable, responding well with no signs of heart failure, no indications
for surgery

Surgical
Should be sought at earliest opportunity for every patient with endocarditis affecting
intracardiac prosthetic material
As compared with conventional treatment, early surgery in patients with infective
endocarditis and large vegetations significantly reduced the composite end point of
death from any cause and embolic events by effectively decreasing the risk of
systemic embolism.

Empirical treatment
NVE
Antibiotic

Dosage and Route

Duration

Comment

Ampicillin-Sulbactam or
Amoxicillin-Clavulanate

12g/day i.v in 4 doses

12g/day i.v in 4 doses

4-6 weeks
4-6 weeks

Patients with blood-culture

negative should be treated in
consultation with infectious
disease specialist

3mg/kg/day i.v. or i.m. in 2-3

doses

4-6 weeks

30mg/kg/day i.v. in 2 doses

4-6 weeks

3mg/kg/day i.v. or i.m. in 2-3

doses

4-6 weeks

With
Genatmicin
Vancomycin
With
Genatmicin
With
Ciprofloxacin

For patients unable to

totlerate beta-lactam

4-6 weeks

Ciprofloxacin not uniformly

active on Bartonella spp.
Addition of Doxycycline if
likely

Comment

1000mg/day orally in 2 doses

or
800mg/day i.v. in 2 doses

PVE
Antibiotic

Dosage and Route

Duration

Vancomycin
With
Genatmicin
With
Rifampin

30mg/kg/day i.v. in 2 doses

6 weeks

3mg/kg/day i.v. or i.m. in 2-3

doses

2 weeks

1200mg/day orally in 2 doses

Staphylococcus spp.
Valve

Strain

Antibioti
c

Dosage and Route

Duration

Prosthetic

Methicillin
susceptible

(Flu)cloxa
cillin
Oxacillin

12g/day i.v. in 4-6 doses

12g/day i.v. in 4-6 doses

>6 weeks

1200mg/day i.v. or orally in

2 doses
3mg/kd/day i.v. or i.m. in 2-3
doses

>6 weeks
2 weeks

With
Rifampin
Gentamic
in

Native

Penicillinallergic
patients OR
methicillinresistant
Staphylococci

Vancomy
cin

30mg/kd/day i.v. in 2 doses

>6 weeks

With
Rifampin
Gentamic
in

1200mg/day i.v. or orally in

2 doses
3mg/kg/day i.v. or i.m. in 2-3
doses

>6 weeks
2 weeks

Methicillin
susceptible

(Flu)cloxa
cillin
Oxacillin

12g/day i.v. in 4-6 doses

12g/day i.v. in 4-6 doses

4-6 weeks
3-5 days

Penicillin-

With
Gentamic
in

3mg/kd/day i.v. or i.m. in 2-3

doses

Vancomy

30mg/kd/day i.v. in 2 doses

4-6 weeks

Oral and Group D Streptococci

Strain

Antibiotic

Dosage and Route

Duration

Penicillin susceptible
standard treatment

Penicillin or
Amoxicillin or
Ceftriaxone

12-18millions U/day in i.v. in

6 doses
100-200mg/kg/day in 4-6
doses
2g/day i.v. or i.m. in 1 dose

4 weeks

Penicillin susceptible
standard treatment and Inbeta-lactam allergic
patients

Vancomycin

30mg/kg/day i.v. in 2 doses

4 weeks

Penicillin susceptible twoweek treatment

Penicillin or
Amoxicillin or
Ceftriaxone

12-18millions U/day in i.v. in

6 doses
100-200mg/kg/day in 4-6
doses
2g/day i.v. or i.m. in 1 dose

2 weeks

With
Gentamicin or
Netimicin

2 weeks
3mg/kg/day i.v. or i.m. in 1
dose
4-5mg/day

Strains relatively resistant

to penicillin

Penicillin or
Amoxicillin

24 million U/day in i.v. in 6

doses
200mg/kg/day in 4-6 doses

With
Gentamycin

4 weeks

2 weeks
3mg/kg/day i.v. or i.m. in 1

Surgery
Indications:
Heart failure
Severe acute regurgitation or valve obstruction causing refractory pulmonary
oedema/shock
Fistula into a cardiac chamber or pericardium causing refractory pulmonary
oedema/shock
Severe acute regurgitation or valve obstruction and persisting heart failure or
echocardiographic signs of poor haemodynamic tolerance (urgent).
Severe regurgitation and no heart failure (elective)

Uncontrolled infection
Locally uncontrolled infection including abscess, false aneurysm, enlarging
vegetation
Persisting fever and positive blood culture for at least ten days after
commencing appropriate antimicrobial therapy
Infection caused by fungi or multiresistant micro-organism

Prevention of embolism
Aortic or mitral IE with large vegetations >10mm, resulting in one or more
emobolic episode despite appropriate antibiotic therapy
Aortic or mitral IE with large vegetations >10mm, and other predicotrs of
complicated course like heart failure, persistent infection or abscess
Isolated very large vegetations >15mm

Prognosis
NVE
S. viridans Cure rates 98%
S. aureus 60-70%, worse for IV abusers
Fungal infections <50%

PVE
Cure rates at least 10% lower than above for each variety
Surgery needed more often

Mortality
NVE 16-27%, PVE higher
Increase with increased age, infection involving the aortic valve,
development of congestive cardiac failure, CNS complications, and
underlying disease e.g. diabetes
Mortality varies with organisms
Acute endocarditis due to S. aureus is associated with high mortality rate 30-40%