Infective endocarditis
Case presentation:
47 year old female patient, she has chronic renal failure and presented
to the clinic with fever for the last three weeks, with chills and rigors,
she has poor appetite, weight loss, fatigue, upper abdominal pain, left
ankle pain and swelling, there is no cough, no sputum production, no
chest pain and no vomiting (means negative review of systems).
*Past medical history was positive for cholecystictomy.
*Drug history:
-Oscal: which is Ca (patients with chronic renal failure take Ca)
-Lanzoprazol: proton pump inhibitor.
-Neurobion: multi vitamins (B complex)
-Motilium: is an antiemetic.
*Blood pressure was 110/70, heart rate 100, temperature was 38 c, and
she was pale, no LN enlargement, normal S1 and S2, there was ejection
systolic murmur and end diastolic murmur at the lower sternal border
and at the apex.
*In the abdomen there is left upper quadrant tenderness, and in the
extremities there is left ankle swelling and no any skin lesions.
*On the chest x-ray there was slight cardiomegaly, and on the ECG
there is sinus tachycardia.
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*Lab results:
-Hb: 9.3

-CR (creatinine): 5.6 which is 5 times the normal

-WBC: 12.9

-CRP: 341

-PLT: 341

-Na: 129

-K: 4.0

-RBS: 135

-ESR: 120 (For a normal female it is about 20 so it is very high)

*Liver function test was normal.
*Urine: +1 protein, +2 blood, 10 12 WBC, 20-24 RBC.
*Abdominal ultrasound was normal
*Trans thoracic echocardiography (TTE): showed +2 mitral regurg, +2
aortic regurg, mild aortic stenosis with pressure gradient of 25(the
normal gradient across the aortic valve is zero), and no vegetations.
*Ejection fraction was 65%.
*Blood culture shows enteroccocus sensitive to ampicillin and
vancomycine.
*She is given ampicillin and gentamicin and she is on dialysis.
Next day she developed pulmonary edema; she is intubated and put on
mechanical ventilator.
After extubation she continued to complain of abdominal pain, the CT
abdomen shows large hypodense splenic lesion, she is planned for
splenectomy today.
The case that we presented was a typical case of infective endocarditis.
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Vegetation is the characteristic lesion (a mass of plt & fibrin in which

abundant microorganisms & inflammatory cells are engorged), usually
infective endocarditis as the name implies affect the endocardium of
the heart; which is the innermost layer of the heart, and the
intracardiac effects of this infection include severe valvular
insufficiency, infection may occur at sites of septal defect, on chordae
tendineae , mural endocardium ,PDA(patent ductus arteriosus) ,
coarctation of aorta.

Diagnosis:
The diagnosis depends on documentation of an organism (by bacteria),
ECHO finding, and the clinical findings.
There are criteria that it is important for the diagnosis of infective
endocarditis which is called DUKE criteria, which Composed of:
2 major, or 5 minor, or 1 major and 3 minors.

Major criteria ;
1) Echo; new vegetation, new valve regurg, abscess, new partial
dehiscence of prosthetic valve.
Partial dehiscence means: when there is an artificial valve and after a while the
valve leaks.

2) Bugs; positive blood culture for typical organisms:

viridans , bovis , s.aureus , enterococcus , HACEK group.
The HACEK group are: Haemophilus aphrophilus,Actinobacillus
actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella
kingae)
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Minor criteria;
1) Predisposing heart condition or IV drug abuse.
2) Fever > 38.
3) Embolic phenomena.
4) Immunological phenomena.
5) Lesser echo or clinical data.

*Embolic phenomena;
1) Major arterial emboli.
2) Septic pulmonary or splenic emboli (like the case we shown)
3) Mycotic aneurism in the brain (cerebral)
4) Janeway lesions (small non tender macular lesions on the palms &
soles).
(The doctor said that it is always come in the exam to differentiate if it is tender or not)

5) subungual ( splinter ) hemorrhage.

*Immunological phenomena;
1) GN
2) Arthritis
3) Oslers nodes (painful nodular lesions on the pulp of the digits)
4) Roths spots (retinal hemorrhage)
5) Renal failure (RF)
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Acute bacterial endocarditis caused by Staphylococcus aureus with aortic valve ring abscess
extending into myocardium.

The mortality of infective endocarditis depends on the bacteria

isolated, and it is around:
10% for viridans strep.
20% for enterococcus.
40% for s.aureus.
50 % p.auroginosa & enterobacteriaceae.
*The blood cultures should be done, 3 blood cultures in 1st 24 hrs;
If bacteremia is present then positive blood culture in 90 % after 2
sets of cultures, the more cultures you do the more the likelihood of
getting an organism during the culture.
HACEK group needs 4 weeks to grow.
And the Serology for Q fever, brucella ,legionella, are documented by
serology tests.
Culture negative endocarditis it is less than 5 % of cases of IE, it is
due to recent use of antibiotics or fastidious organisms like the
HACEK group, or fungal infections, sometimes caused by intracellular
parasite infections like chlamydia or brucella.

Treatment:

Strep viridians: penicillin,ceftriaxone,vancomicin + gentamicin

Enterococci: ampicillin + gentamicin

S.aureus: vancomicin + gentamicin
As we mentioned that the treatment for endocarditis is by giving
antibiotics, but the question is: do we need to do surgery for a patient
with infective endocarditis?

There are certain criteria (Definite indications);

1) Acute valvular dysfunction with hemodynamic instability, for
example aortic valve endocarditis with acute aortic regurg needs
emergent surgery.
2) Intractable congestive heart failure symptoms.
3) Persistent infection in spite of antibiotic therapy (after 3 weeks if
there is still a positive blood culture we need to consider surgery)
4) Myocardial invasion, when endocarditis turn to become an abscess
that extends to the bundle branches causes 1st degree to 3rd degree
heart block, such a type of infection needs surgical intervention
because antibiotics will not be enough.

Other indications;
1) Recurrent endocarditis
2) Recurrent embolization
3) Abscess formation
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4) Fungal endocarditis
5) Prosthetic valve endocarditis
The doctor asks why endocarditis is difficult to treat?
One factor is that endocarditis usually caused by the worst and
strongest microorganisms.
The other factor that the cardiac valves are devoid from blood vessels
and the media to transfer the antibiotic to any place in the body is by
the blood, and the blood is not reaching there well, it is only reaches
the bases of the cusps, so it is difficult to treat it by antibiotics alone.

Rheumatic fever
Acute rheumatic fever is an inflammatory disease with devastating
sequeale, and it is linked to pharyngeal infection with group A beta
hemolytic streptococci.
It continues to be a problem worldwide:
Sporadic outbreaks in developed countries, in the past in developed
countries rheumatic heart disease was the main cause for valvular
heart disease, in the last 30 years the generative causes are the most
common causes of valvular heart disease in the west, and no more
rheumatic fever is considered as a leading cause of valvular heart
disease.
On the other hand there are still places in the developing countries
where rheumatic fever is still the leading cause of valvular heart
disease, luckily not in Jordan.

Still gaining understanding of etiology, there is a link between genetic

predisposition and clinical manifestations.
The best prevention still use of antibiotics.
Regarding the epidemiology:
It is an important cause of chronic disease and death in the developing
world, it is under diagnosed and under treated, and it is estimated that
30 million people suffer from ongoing heart disease from acute
rheumatic fever, 70% dying at average age 35 years old.
It usually occurs in people between 5 and 18 years old, males and
females are equally affected, overcrowded, poverty, lack of access to
medical care contribute to transmission.
It depends on the virulence of the strain of group A beta hemolytic
streptococci, in the tropic and sub tropic areas the year-round
incidence with peaks in colder months.

The pathogenesis:
Group A streptococci pharyngeal infection precedes clinical
manifestations of acute rheumatic fever by 2-6 weeks.
The antibodies made against group A streptococci cross react with
human tissue (heart valve and brain share common antigenic
sequences with GAS bacteria).
There is a theory of molecular mimicry:
There is an antigen in group A streptococci in its cell wall called M
antigen, it is thought that it cross react with the M antigen in the heart
and because of this mimicry the disease occurs.
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The host immune response may play a role in determining who develop
ARF following infection.
*The virulent strains are the rheumatologic serotypes.
*And the most important antigenic proteins in the external layer of the
cell wall are the M,T,R proteins.

Clinical features:
Following upper airway infection with GAS, there is a silent period of 26 weeks, and sudden onset of fever, malaise (feeling of ill being), pallor,
and fatigue.
It is characterized by:
1) Arthritis 2) Carditis 3) Sydenhams chorea 4) Erythema
marginatum 5) subcutaneous nodule
They are called major manifestations of jones criteria either because of
frequency or specifity.
* The doctor here insists on the importance of the criteria of infective
endocarditis and rheumatoid fever and differentiating between them.

Other features:
1) Arthralgias

3) Serositis

2) Epistaxis
*Involvement of the lung, kidneys, and CNS.

Arthritis:
The most common feature present in 80% of patients.
*It is painful, migratory, short duration, excellent response to
salicylates.
*usually more than 5 joints are affected and large joints preferred;
Knees, ankles, wrists, elbows, shoulders.
*Small joints and cervical spine are less commonly involved.

The end of the first part

Done by: Omar Abu Farsakh

10

HADI'S PART

Carditis:

The major criteria are:

- Carditis
- Arthritis
- Sydenham's chorea
- Erythema marginatum
- Subcutaneous nodues

-Most serious manifestation that can lead to death

within 1-2 weeks.
Acute valvular dysfunction acute heart failure DEATH

.
-Any cardiac tissue may be affected (endocardium + myocardium + pericardium)
---valvular lesions are the most common specially mitral and aortic valves.
---Seldom see isolated pericarditis or myocarditis alone without valves lesions.

THE CLINICAL SIGNS:

-High pulse rate: in the past the drs were diagnose RF by watching the pt
while he is sleep to check for tachycardia
-Murmurs: we check for new murmurs; we consider mitral regurgitation so
we hear a systolic murmur in the apex of the heart.
-Cardiomegaly: by chest x-ray.
-Rhythm disturbances (prolonged PR interval)
Q: in spite of tachycardia there is prolonged PR interval. Whyyyyyyyy?
A: because of block (first degree) in the AV node and this is because the
rheumatoid fever is an inflammatory process affect the endocardium and
the valves; and the aortic valve is very close to the AV node so when the
valve become inflamed and enlarged it will affect the AV node.
-Pericardial friction rubs: when there is pericarditis.
-Cardiac failure: that cause pulmonary edema and lower limb edema as a
manifestations.
-Mitral and aortic regurgitation most common you can hear apical systolic (related
to the apex) and basal diastolic murmurs (related to the base of the heart where
the great vessels orginates).
-Pericarditis usually asymptomatic and occasionally causes chest pain, friction
rubs or distant heart sounds (distant because of the pericardial effusion the
sounds are muffled).
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NOTE: if the pt has pericardial effusion on the echo and you can't hear the heart
sounds this indicates that the amount of the effusion is significant.

This chest X-ray for a pt with RF and you can see Cardiomegaly ( the cardio-thoracic
ratio more than 50%).

Sydenhams Chorea:
 Extrapyramidal disorder characterized by fast, clonic, involuntary
movements (especially face and limbs) and the pt looks like dancing.
 Muscular hypotonus
 Emotional liability: crying then smilingetc.
 The First sign starts with difficulty in walking, talking, writing
 Usually Sydenham's Chorea is a late manifestation occure months after
the infection.
 rarely the only manifestation of ARF.
 Occurs in 30% of patients with ARF and can return back after the pt recovered
from the ARF.
 1/2 of these (30%) also have carditis (more common with sydenham's chorea) or
arthritis.
 Usually benign and resolves in 2 - 3 months and can last for more than 2 years.

Subcutaneous Nodules:
Usually 0.5 - 2 cm long, Firm, non-tender, isolated or in clusters.
Most common: along extensor surfaces of joint (Knees, elbows, wrists); just
move your hand over the skin and you will feel the nodules. Also you find it on
bony prominences, tendons, dorsi of feet, occiput or cervical spine.
Last a few days only and Occur in 9 - 20% of cases.
Often associated with carditis (always if you found subcutaneous nodules then
the pt 100% has carditis).

Erythema Marginatum:

(begin as small dot then increase in size)

Present in 7% of patients

Highly specific to ARF

Cutaneous lesion: Reddish pink border, Pale center, Round or irregular shape.

Often on trunk, abdomen, inner arms, or thighs.

Highly suggestive of carditis

Erythema marginatum : notice the pink border and the pale in the center.

Other Clinical Features: Less frequent or less specific to ARF

-fever

-Arthralgia instead of arthritis

-Epistaxis

-Abdominal pain (5%) due to peritonitis (because of serositis Inflammation of the

serous tissues of the body. The serous tissues line the lungs (pleura), heart (pericardium), and the
inner lining of the abdomen (peritoneum) and organs within).
-Hematuria

(5%) because of renal involvement and when we do routine biopsy in

pts with ARF we find 40% of them have renal involvement.

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-Pneumonitis

-Mild pleuritis (5 - 10%)

-Encephalitis (extremely rare).

DIAGNOSIS
In the diagnosis we follow jone's criteria which is:-

Criteria developed to prevent overdiagnosis

Some criticism regarding validity

Still important as guidelines

Probability of ARF high with:

 Evidence of previous infection with streptococcal upper airway infection we do a
throat swap then culture and look for group A streptococci.
 2 major criteria
 1 major criteria and 2 minor criteria

Evidence of Previous Infection:

o Culture: the gold role to isolate the group A
streptococci.

The minor criteria are:

-Fever
-Arthralgia
-Elevated c-reactive protein
- Erythrocyte sedimentation
rate
-Prolonged PR interval on ECG

o Antistreptolysin antibody: less sensitive for

RF; often elevated in healthy children or
with Rheumatoid Arthritis, Henoch-Schonlein Purpura, Takayasus Arteritis.
o Antibodies to other strep antigens like Anti-DNAase B, anti-hyaluronidase, antistreptokinase, anti-nicotinamide.
the

dr

here

slides so I will
some notes.

begin to skip a lot of

The Differential Diagnosis of ARF:

put them and add

Juvenile rheumatoid arthritis

Systemic lupus erythematosus
Other connective tissue diseases, including vasculitidies
Bacterial endocarditis
Reactive arthritis
Seronegative spondyloarthropathies
Infections (Hansens Disease, Lyme, Yersinia)
Familial Mediterranean Fever
Antiphospholipid Syndrome
Leukemias
Sickle cell anemia and other hemoglobin disorders
Sarcoidosis

Laboratory Studies
- None capable of diagnosing ARF: clinical
diagnosis
- Can help eliminate other diseases
- Aids in diagnosis
- Monitor inflammatory process
- Evaluate extent of cardiac involvement
- CBC: not very helpful we can see leukocytosis
- increase CRP, increase ESR: non-specific indicators of inflammation
- Tests for anti-streptococcal antibody
- CXR for cardiomegaly
- EKG: prolonged PR interval in 1/3 patients
 not specific to ARF
 not associated with later cardiac sequelae

TREATMENT
The treatment of ARF depends mainly on the Eradication of the group A strep,
and the best treatment is a sigle dose of IM benzathine penicillin G acts for
month. We give the dose for pts >27 kg 1,200,000 units and for pts <27 kg
600,000 units.

Other alternatives
-

PCN VK 500 mg - 1000 mg divided bid to qid x 10 d

Erythromycin 40 mg/kg/d divided bid to qid x 10 d
Azithromycin x 5 d
Cephalosporins x 5 d
Cefuroxime axetil
Cefpodoxime proxetil
Cefadroxil
Cefdinir
- NOT sulfa-derived antibiotic: do not eradicate strep

For arthritis:
-

Salicylates we use them in high dose 600mg/kg or NSAIDs x 3 weeks

Usually excellent response

- If poor response: diagnosis in question

For Carditis:
- Pts with Carditis its recommended to take steroids beside aspirin.
-

Prednisone 1 -2 mg/kg/d (max 60 mg) x 10 - 15 days.

If simultaneous arthritis and carditis: steroids alone sufficient but most

cardiologist starts with aspirin.

For Sydenham's chorea:

-

Haloperidol (anti psychotic) 0.5 - 1 mg/kg

Alternate: Sodium valproate (anti epileptic) 15 -20 mg/kg/d
No proven benefit of steroids (steroids just with arthritis and carditis).

primary prophylaxis:
we mean by primary prophylaxis is to give the treatment before having the
disease, but the secondary prophylaxis is to prevent the complications and the
recurrence of the disease.
We use antibiotics (penicillin) as we said, and in Jordan we apply roles to
-

Improving living conditions ( 


 for more info. Watch 8:00 pm
news 3la jordan tv)

Hygiene     !  ...

 


Overcrowding

Access to medical care

Education #%  &'

(  ) + ,-! 

Secondary prophylaxis
Benzathine PCN given to prevent recurrences of ARF and to prevent any chronic valve
disease, studies shows that pts with ARF when they treated they get what we call it
chronic smoldering (it means that there is a disease but progress very slowly).

Pts with valvular disease (mitral regurge or stenosis or aortic regurge) we give them
lifelong penicillin treatment.

Conclusions:
-

Acute Rheumatic Fever leading to Rheumatic Heart Disease is a major

problem world wide.
Appropriate treatment of group A strep pharyngitis necessary to prevent
disease.
Preventing recurrences causing chronic heart disease is simple, universally
available, and cost effective.

THE END
Best regard to all group A9 every one of them except sheikh el group Saleh Abu
Lebdeh( from Omar )

Done by: Hadi Al Radaideh & Omar Abu Farsakh

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