Al-Bayan University / College of Pharmacy

Pharmacology & Toxicology Dept. 2019-2020

Fourth stage / Clinical Pharmacy II - Lecture 9 / presented by
Dr. Atheer S. Alsabah

Infective Endocarditis

 Infective endocarditis (IE) is a serious infection affecting the lining & valves of
the heart. Bacteria is the primary cause of IE; however, fungi & atypical
organisms also can be responsible pathogens.
- Typically IE is classified into acute or subacute. This difference has been based on
the progression & severity of the disease.
a. Acute disease is more aggressive, ccc by high fever, elevated WBC counts, &
systemic toxicity, with death occurring within a few days to weeks. This type
often is caused by more virulent organisms, particularly Staphylococcus aureus.
b. Subacute disease typically is caused by less virulent organisms, such as viridans
streptococci, producing a slower & more subtle presentation. It is ccc by
weakness, fatigue, low grade fever, night sweats, weight loss, & other nonspecific
symptoms, with death occurring in several months.

Figure: IE (bacterial) A, Endocarditis of mitral valve (subacute, caused by Strep. viridans), the
large friable vegetations are denoted by arrows.
B, Acute endocarditis of congenitally bicuspid aortic valve (caused by Staph. aureus) with
extensive cuspal destruction & ring abscess that denoted by arrow.

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• Etiology
1. Nearly every organism causing human disease has been reported to cause
infective endocarditis, but three groups of organisms result in a majority of cases:
streptococci, staphylococci, & enterococci.
2. Streptococci & staphylococci are the cause of 80% to 90% of cases of IE.

• Risk factors
- Most persons with IE have risk factors, such as preexisting cardiac valvular
abnormalities. A predisposing risk factor, however, may be absent in up to 25% of
cases. Some of the more important risk factors include:
1. Presence of a prosthetic valve (highest risk).
2. Previous endocarditis (highest risk).
3. Congenital heart disease.
4. Diabetes mellitus.
5. Healthcare-related exposure.
6. Acquired valvular dysfunction (e.g., rheumatic heart disease).
7. Mitral valve prolapses with regurgitation.
8. Intravenous drug abuse (IVDA).

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• Pathogenesis and Pathophysiology
- Endocarditis is usually consequence of
2-factors; the presence of organisms in
the bloodstream & a damaged or
abnormal cardiac endothelium,
facilitating their adherence & growth.
1. Platelets & fibrin now deposit on the
damaged endothelium or valves,
forming a nonbacterial thrombotic
endocarditis (NBTE).
2. At this point, bacteria through
hematogenous spread (bacteremia)
adhere to & colonize this area forming
a vegetation.
3. Further deposits of platelets & fibrin
cover the bacteria, providing a
protective coating that allows for the
development of a suitable environment
for continued organism & vegetation
progression.

4. With the progressive development of a vegetation, function of the heart valve is

impaired. Regurgitation or insufficiency of the affected valve most commonly
results, leading to volume overload of the ventricular chamber. In case of rapid
development of regurgitation, there may be an acute, severe pulmonary edema &
cardiogenic shock may quickly occurs.

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5. Vegetations may be friable, &
fragments may be released
downstream. These infected
particles, termed septic emboli, can
result in organ abscess or infarction.
- Septic emboli from right-sided
endocarditis commonly lodge in the
lungs, causing pulmonary abscesses.
While emboli from left-sided
vegetations commonly affect organs
with high blood flow, such as
kidneys, spleen, & brain.

• Clinical Presentation
a. Fever is low grade & remittent.
b. Cardiac murmur in 90% of pts (heart murmur is an unusual sound made by
turbulent blood flow, sometimes as a result of valve disease). Over 90% of pts
who have a new murmur will develop heart failure, which is a major cause of
morbidity & mortality.
c. Arthralgia, myalgia, low back pain, & arthritis.
d. Fatigue, anorexia, weight loss, & night sweats.
e. Cutaneous manifestations (50% of pts):
1. Petechiae are very small (usually less than 3 mm) pinpoint flat red spots beneath
the skin surface caused by micro-hemorrhaging found on the buccal mucosa,
conjunctivae and extremities.

2. Splinter hemorrhages appear as small dark streaks beneath the finger or toenails.

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3. Clubbing of the finger tips typically occurs in long-standing illness and is present
in approximately 10% to 20% of patients.

4. Osler nodes are small (usually 2–15 mm), painful, tender subcutaneous nodules
located on the pads of the fingers and toes.

5. Janeway lesions are small, painless hemorrhagic plaques on the palms of the
hands or soles of the feet and more commonly associated with acute S. aureus IE.

6. Roth spots are rarely occurring (in less than 5% of IE cases), oval-shaped retinal
hemorrhages with a pale center near the optic disc.

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• Laboratory findings
1. Anemia (normochromic, normocytic).
2. Leukocytosis.
3. Elevated erythrocyte sedimentation rate (ESR) & C-reactive protein (CRP).
4. Positive blood culture in 78%–95% of pts.
5. Echocardiography to determine the presence of valvular vegetations plays a key
role in the diagnosis of IE; it should be performed in all suspected cases.

• Complications
a. CHF in 38%–60% of pts.
b. Emboli in 22%–43% of pts.

• Treatment
- Desired outcome:
1. Relieve the signs & symptoms of disease.
2. Decrease morbidity & mortality associated with infection.
3. Eradicate the causative organism.
4. Prevent IE in high-risk pts with appropriate prophylactic antimicrobials.

- Non-pharmacologic therapy:
Surgery (repair of the native or valve replacement) is an important adjunct to
management of endocarditis in certain pts. In most cases, valvectomy & valve
replacement are performed to remove infected tissues.

- Antimicrobial therapy:
 General principles
- Without antimicrobial therapy & surgical intervention, IE is virtually 100% fatal.
- There are three basic principles of antibiotic treatment of IE:
1. Prolonged course of antibiotics (4 - 6 weeks) is necessary because bacterial
concentration within vegetations is high & organisms deep within valvular
vegetations are inaccessible to phagocytic cells.
2. Parenteral administration of antibiotic therapy is necessary to achieve adequate
drug levels required to eradicate infection.
3. Combination therapy typically involving β-lactam & aminoglycoside antibiotics is
recommended, because of the need for prolonged therapy & rising antimicrobial
resistance among organisms.

 Empiric treatment
- Empiric treatment of IE should include antimicrobials that are effective against
the most commonly encountered organisms (i.e. streptococci, staphylococci, &
enterococci as in table 3 below). When blood cultures are positive, treatment
should be directed toward the organism that is isolated.

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 Organism specific therapy

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a. Streptococcal Endocarditis
- Streptococci are a common cause of infective endocarditis, with most isolates
being viridans streptococci. These bacteria are common inhabitants of the human
mouth and gingiva, and they are especially common causes of endocarditis
involving native valves. During dental surgery, and even when brushing the teeth,
these organisms can cause a transient bacteremia. In susceptible individuals, this
may result in infective endocarditis.
b. Staphylococcal endocarditis
- It is important to determine whether the isolate is methicillin-susceptible or
methicillin-resistant & whether the pt has a prosthetic valve.
c. Enterococcal endocarditis
- Enterococci cause 5% to 18% of endocarditis cases. They are resistant to all
cephalosporins & relatively resistant to aminoglycosides. Combinations of a cell
wall–active agent, such as a penicillin or vancomycin, plus an aminoglycoside are
necessary for killing.

• Prognosis
- Mortality % is 30% staphylococci; 14% enterococci; & 6% sensitive streptococci.

• Prevention of Endocarditis
- The objective of prophylaxis is to diminish the likelihood of IE in high-risk
individuals who are undergoing procedures that cause transient bacteremia;
therefore endocarditis prophylaxis is recommended for all dental procedures that
involve manipulation of the gingival tissue or perforation of the oral mucosa.
- Cardiac conditions associated with the highest risk of adverse outcome from
endocarditis (which required prophylaxis with dental procedures) are include
prosthetic cardiac valves, previous IE, & congenital heart disease.
Antibiotic Regimens for a Dental Procedure
Situation Agent Regimen: single dose 30 - 60min before
procedure
Adults Children
Oral Amoxicillin 2g 50 mg/kg
Unable to take oral Ampicillin 2 g IM or IV 50 mg/kg IM or IV
medication
Or Cefazoline or 1 g IM or IV 50 mg/kg IM or IV
ceftriaxone
Allergic to penicillins Cephalexin a,b 2g 50 mg/kg
(oral)
Or Clindamycin 600 mg 20 mg/kg
Or Azithromycin or 500 mg 15 mg/kg
clarithromycin
Allergic to penicillins & Cefazoline or ceftriaxone 1 g IM or IV 50 mg/kg IM or IV
b
unable to take oral
medication
Or Clindamycin 600 mg IM or IV 20 mg/kg IM or IV