3.31.09 Pillinger. Pseudomonas

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    Pseudomonas Aeruginosa

    A basic review

    A Basic Review

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    The basics

    Aerobic, opportunistic pathogen

    Gram-negative bacillus

    Flagella

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    Pathogenesis

    Virulence Factors (structural components)

    Alginate

    Adherence proteins and pili

    Lipopolysaccharide (LPS)

    Procyanin

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    Structure

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    Structural Components

    Adherence to host cells mediated by pili and nonpilusadhesins.

    LPS (lipopolysaccharide) inhibiting antibiotic killing and

    suppress neutrophil and lymphocyte activity

    Alginate mucoid exopolysaccharide that forms a shinybiofilm protecting from antibodies, complement,

    phagocytosis, and antibiotics

    Procyanin impairs ciliary function, mediates tissuedamage through production of oxgen radicals

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    Pathogenesis

    Virulence Factors (toxins and enzymes):

    Exotoxin A

    Exoenzyme S Endotoxins

    Phospholipase C

    Elastase and Alkaline Protease

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    Exotoxin A

    Similar in structure to Diptheria toxin

    Inhibits protein synthesis by ADP-ribosylating

    EF-2 (G-protein)

    Causes Dermatonecrosis in burn wounds,corneal damage in ocular infections, and tissue

    damage in chronic pulmonary infections.

    Also this toxin is immunosuppressive

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    Exoenzyme S & T

    ADP-ribosylates G-proteins including p21RAS interfering with host cell growth

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    Phospholipase C

    Heat labile hemolysin

    Breaks down lipids and lecithin causingtissue destruction

    Stimulates inflammatory response

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    Elastase and Alkaline Protease

    Destruction of elastin-containing tissues(blood vessels, lung tissue, skin), collagen,immunoglobulins, and complement factors

    Can produce hemorrhagic lesions(ecthyma gangrenosum) associated withdisseminated infection

    Inactivation of interferon and TNF-Alpha

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    Epidemiology

    Ubiquitous in moist environmental sites inthe hospital as well as nature

    No seasonal incidence

    Can transiently colonize the respiratory

    and GI tract of hospitalized patients

    Minimal nutritional requirements and can

    tolerate broad temperature spectrum

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    Clinical Disease

    Pulmonary Infections

    Burn Wound Infections and other skin and soft tissueinfections (life threatening)

    UTIs (especially catheterized)

    External Otitis (malignant OE, swimmers ear)

    Eye Infections and corneal ulceration via contaminatedcontact lens cleaning fluids

    Pseudomonal Endocarditis

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    Pulmonary Infections

    Can range from asymptomatic colonization to severe necrotizingbronchopneumonia

    Colonization is seen in patients with cystic fibrosis, chronic lungdisease, and neutropenia

    Mucoid strains are commonly isolated from chronic pulmonarypatients and are more difficult to eradicate

    Predisposing conditions include previous therapy with broadspectrum abx (disrupts normal protective bacteria population and

    use of respiratory therapy equipment (can introduce the organism tolower airways)

    Mortality rate can be as high as 70% for invasive bronchopneumonia

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    Pseudomonas PNA

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    Ecthyma Gangrenosum

    Ecthyma gangrenosum is a wellrecognized cutaneous manifestation ofsevere, invasive infection by

    Pseudomonas aeruginosathat is usuallyseen in immunocompromised, burnpatients, and other critically ill patients

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    Echtyma Gangrenosum

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    Malignant Otitis Externa

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    Pseudomonas Keratitis andCorneal Ulceration

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    Endocarditis

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    Antibiotic Resistance

    Inherently resistant to many abx

    Can mutate to more resistant strains duringtherapy

    Penetration of abx highly dependent on outermembrane pores which can be altered

    Production of B-lactamases

    Combination of active abx generally required forsuccessful therapy