Intravascular Infection:Microorganisms gain entry to the intravascular system throughout:1-The cellular components of blood.

2-The structural elements of the circulatory system.

Examples:-Plasmodium species, Babesia microti invades RBCs.

-HFVs infects the endothelial surface of cardiovascular components.

Definitions: Endarteritis: intravascular infection of artery. It is associated with: 1-Congenital arterial anomaly; ductus arteriosus. 2-Diseased arterial endothelium; atherosclerotic plaques.

Phlebitis: infection of the lumen of vein ; It is directly correlated with: 1-Direct spread from an adjacent focus of infection. 2-Intravascular foreign bodies (catheter) implanted in vein.

Infective Endocarditis: -Is an infection of the endocardial surface of the heart.-It is localized on the cardiac valves, the atrial or ventricular wall ,and the chordae tendineae.-Arise as a consequence of cardiac surgery or intra-cardiac instrumentation, and bacteremia.

Classification of Endocarditis:

1-Infective. 2-Non-Infective. Or:1-Acute: febrile , toxic illness lasting only days to several weeks.2-Subacute: lower fever, anorexia, weakness, weight loss, and are symptomatic for longer than several weeks.

Epidemiology:-Infective endocarditis accounts for 1 in 1000 admissions to large general hospitals.-More than 50% of cases involve people older than 50 years of age.

N

The common predisposing factors for endocarditis are:1-Congenital cardiac defects: -Bicuspid aortic valves, ductus arteriosus, or ventricular septal defects.2-Degenerative valvular diseases.

3-Acute Rheumatic fever: Streptococcal M protein Cross-reactivity with cardiac myosin.

4-Prosthetic heart valves.

5- Cardiac rhythm management device (CRMD).

n

Causes of Infective endocarditis:

-Left sided endocarditis are most common, accounting for

95% of cases.

-Right sided endocarditis accounts only for 5% of cases.

Causes of endocarditis:1-Native valve endocarditis: A-Acute : Staphylococcus aureus accounts for 60% of cases. 40% include alpha-Streptococcus and G-ve bacilli. Average mortality rate is 20%.

Higher in patients over 65 years of age.

N

B-Subacute: -Alpha-Streptococci and non-hemolytic accounts for 60%. -40% include Enterococcus, Coagulase negative Staphylococcus species, fastidious Gram negative bacilli.

-Among injection drug users (younger persons): -Staphylococcus aureus causes 75% of right-sided endocarditis.

-Whereas a wide range of microbes cause left-sided endocarditis; 25% Staph aureus, 40% Streptococci and Enterococci, 18% fungi and Gram negative bacilli.

N

2-Prosthetic valve endocarditis: Depends on the time after surgery when infection becomes symptomatic.

A-Nosocomial acquired endocarditis: -50% of cases caused by Staphylococcus aureus. -Gram negative, Corynebacterium, and fungi.

B-Community acquired endocarditis: -It occurs as a consequence of bacteremia. -It is acquired in the first year after valve replacement. -Staphylococcus aureus, Staphylococcus epidermidis (Beta-lactam resistance), and Streptococci.

Pathogenesis and Microbial virulence factors:-Only a limited types of bacteria can cause endocarditis.-Microbial invasion into bloodstream (bacteremia).

Microbial agents(Bacteremia)

Plasma ProteinsCoagulation factors

Thrombotic VegetationHost defense

Endothelium adhesion, Bacterial

Vegetation

N

-Microbes reach the cardiac valve.

-Microbes resist complement-mediated bactericidal

activity and escape phagocytosis.

-Primary damage of valve endothelium; cytokines;

expression of Beta1 integrin by endothelium; binding of

plasma fibronectin ; coagulation and formation of sterile

vegetation (Platelet-fibrin aggregates);

(non-bacterial thrombotic vegetation).

N

-Increased microbial adhesion;

-Alpha-hemolytic Strpetococci species produce

extracellular dextran and Fim A adhesin that bind

strongly to fibronectin and thrombotic vegetation.

-Enterococci lipoteichoic acid promotes similar adhesion.

-Staphylococcus aureus fibrinogen binding protein initiate

the microbial adherence to thrombotic vegetation.

-Formation of bacterial vegetation (108 to 109 CFU/gm).

N

-Colonization of heart endocardium due to: 1-Endothelium tissue factors; formation of thrombin. 2-Destruction of endothelial cells by thrombocidins.

-Bacterial vegetation occurs

along the edges of the heart

valves, on the ventricular side

of mitral and aortic valve

and on the atrial side of

tricuspid valve.

N

Microscopically, Bacterial vegetation is a mass

of platelets, fibrin, Micro-colonies of microbes, and

inflammatory cells.

In the subacute form of infective endocarditis, the

vegetation also include:

a center of granulomatous

tissue, which may undergo

fibrosis (collagen) or

calcification.

N

-In 25-35% of cases, Infective endocarditis is associated

with fragmentation of vegetation into the circulation,

causing peripheral septic emboli.

-Visceral organs and brain

involvement.

-Continuous bacteremia.

-Formation of antibodies complexes; serum sickness

disease (focal embolic glomerulonephritis).

Diagnosis of infective Endocarditis:

Direct : Microbiology:1- Blood culture results have a 95% sensitivity.2-Surgically removed vegetation analysis by culture and PCR.

Indirect: Serology:-Serologic testing have led to identification of :

Rickettsia species, Coxiella species, and Bartonella as

infrequent but important causes of subacute

endocarditis.

Non-infective Endocarditis:

This form occurs more often in patients with Lupus erythematosus and is thought to be due to the deposition of immune complexes.These immune complexes form small sterile vegetation.

Bacteremia:

Bacteremia is the invasion of bloodstream by bacteria.

The blood is normally a sterile environment, so the

detection of bacteria in the blood is always abnormal.

Bacteria can enter the bloodstream as a severe

complication of mucosal surfaces colonization or surgical

procedures:

1-Dental extraction. 2-Gingival surgery.

3-Air way infection. 4-GIT, UTI (endoscopy, catheter)

Septicemia:

Septicemia (sepsis) : is the invasion of bloodstream by

virulent microbe and its toxins which results in acute

systemic illness.

Septic shock: is a medical emergency caused by decreased

blood flow and oxygen delivery to organs and tissues as a

result of inflammatory response against blood sepsis.

It can cause multiple organ dysfunction syndrome and

death.

N

-The mortality rate from septic shock is approximately 25%- 50%.

Microbial virulence and pathogenesis(Sepsis and septic shock):

-The Gram negative lipopolysaccharide bind to LPS-binding

protein which crosslink CD14 in blood.

-Blood monocyte, and neutrophils discriminate the

complexes by CD14 receptors.

-Lipopolysaccharide is a polyclonal B lymphocyte activator.

N

-Production of cytokines in bloodstream; (IL-1, IL-8, IL-12,

TNF).

-Systemic Vasodilation of capillary endothelium, and

Vasoconstriction in the vasculature; edema and chemotaxis.

-Decreased blood pressure, increased smooth muscle

contraction of respiratory tract.

-Rapid breathing, low blood pressure, fever, and lethal

shock.

Sources of Bacteremia:

In the hospital, indwelling catheters are a frequent cause

of bacteremia, because they provide a means by which

bacteria normally found on the skin can enter the

bloodstream.

Other sources of bacteremia include: Dental

procedures ,Urinary tract infection, Respiratory tract

infection, GIT infection, intravenous drug use,

Contaminated endoscopy or colonoscopy, Post-operative

infection.

Causes of Bacteremia and Sepsis:

1-Gastrointestinal infection:

Typhoid fever (Salmonellosis), Malta fever (Brucellosis),

Yersinia infection and Bacteroid fragilis.

2-Genitourinary tract infection:

Staphylococcus aureus, E.coli, Klebsiella, Citrobacter,

Enterobacter, and Pseudomonus species.

Treponema pallidum, and Neisseria gonorrheae.

N

3-Respiratory tract infection:

Neisseria meningitidis, H. influenza, Streptococcus

pneumoniae, MRSA, VRE, and Klebsella pneumonia.

Diagnosis of endocarditis and Bacteremia:Blood culture:A- a 5-8 ml blood should be extracted for culture.B- Specimens should be extracted during fever stage.C- Inoculation of blood culture bottle, and incubation under aerobic and anaerobic conditions at 37C for up to 8 days.

Blood culture procedure:N

Blood culture growth indicators:

1-Turbidity of blood culture media.2-Air bubbles formation in the media.3-Hemolysis of cultivated blood.

Identification of pyogenic Cocci isolated from Blood culture:n

Staphylococcus species:

DNase postive Staphylococcus aureus Coagulase positive

N

Streptococcus viridans species are resistant to Optichin and insoluble in bile salt.