opportunistic infections

Question 1

1. Define the terms Opportunistic, Nosocomial and Iatrogenic infections.

Answer 1

Opportunistic: an infection that occurs in a compromised host by an organism (bacteria, fungus, parasite or virus), which does not usually infect a “normal” host. Nosocomial: Occurs in institutional setting (hospital, nursing home). Iatrogenic: Results from activity of physician or health care giver.

Question 2

Causes of granulocytopenia and resulting opportunistic pathogens

Answer 2

Low PMNS- Chemo or radiation. Gram negatives (e coli, pseudomonas aeruginosa, klebsiella pneumoniae) and staphylococcus

Question 3

Causes of cellular immune dysfunction and resulting opportunistic pathogens

Answer 3

AIDS, age, smoking, T cell defects. Intracellular pathogens like salmonella, m. Tuberculosis and avium, listeria monocytogenes. Also VZV, CMV, HSV

Question 4

Causes of humoral immune dysfunction and resulting opportunistic pathogens

Answer 4

Aggamaglobulinemia, splenectomy. Encapsulated pathogens like s. pneumoniae, H. flu and meningococci

Question 5

opportunistic pathogens associated with foreign bodies

Answer 5

gram negatives, staphylococcus

Question 6

opportunistic pathogens associated with surgery

Answer 6

staph, e coli and pseudomonas

Question 7

iron and bacterial virulence

Answer 7

Excess Fe2+ is highly toxic due to the Haber-Weiss Fenton. Fe2+ catalyzes the production of hydroxyl-radicals. Bacteria also require iron for growth

Question 8

Host defenses involving iron

Answer 8

1. Iron Binding Proteins - Transferrin, Lactoferrin. 2. Shunt Incoming Iron into Storage (e.g. liver). 3. Decrease Iron Adsorption (e.g. from the intestine). 4. Decrease Expression of Microbial Iron Binding compounds (i.e. siderophores). As fever increases, synthesis decreases

Question 9

Microbial mechanisms to scavenge iron from the host

Answer 9

1. siderophores bind iron. 2. receptors to steal siderophores from normal flora bacteria. 3. reductase enzymes free iron from host iron binding systems. 4. receptors bind host heme or lactoferrin and utilize iron directly. 5. microbial toxins kill eukaryotic cells to release Fe. 6. proteases degrate host iron bidning proteins

Question 10

Describe Acinetobacter baumannii infections

Answer 10

gram negative organism in the soils of Iraq. Causes infections of wounds, leading to sepsis. Risk factors include invasive procedures, wounds, hospitalization, antimicrobials

Question 11

7. Discuss the virulence factors of Pseudomonas aeruginosa that contribute to its pathogenesis, and describe where (what organ) and under what conditions (kind of infection) these virulence factors are more significant than others.

Answer 11

P. aeruginosa only adheres well to altered mucosal surfaces (as in CF patients) and poorly to these locations in healthy persons. This bacteria has a specialized capsule that allows it to colonize damaged heart valves.

Question 12

List bacteria with specialized capsules

Answer 12

P. aeruginosa, S. aureus, strains of oral Streptococci – enhanced colonization of damaged heart valve - endocarditis

Question 13

List bacteria that produce urease

Answer 13

Proteus mirabilis, Staphylococcus saprophyticus, Klebsiella aerogenes, E. coli - associated with urinary tract infections (UTI) and kidney stones. H. pylori and stomach ulcers

Question 14

Functions of endotoxin

Answer 14

LPS or LOS on gram negatives- contributes to septic shock. At high doses it sets off a cascade where it stimulates macrophages (primary effector cells) to release TNF then interleukins. These cytokines taget endothelial cells (primary targets) which act as effector cells. fever, hypothension, disseminated blood clotting and lethal shock can result. Other mediators of shock include Hageman factor, prostaglandins, and NO.

Question 15

Types of pseudomonas aeruginosa infections and the predisposing conditions

Answer 15

1. superficial skin- skin abrasion. 2. Chronic ear- diabetes. 3. Sepsis- burns, chemotherapy. 4. necrotizing gastroenteritis- premature newborn. 5. acute pulmonary- post-surgical. 6. chronic pulmonary- Cystic fibrosis.

Question 16

Issues relating to treatment of P. aeruginosa infections

Answer 16

High innate resistance mechanisms (many efflux pumps).Propensity to form biofilms

Question 17

common sources of pseudomonas aeruginosa

Answer 17

whirlpools, swimming pools, hot tubs, loofah sponge

Question 18

ecthyma gangrenosum

Answer 18

pathognomonic of P. aeruginosa septicemia. gun-metal gray, infarcted lesion with surrounding erythema . Evolves into a necrotic black or gray-black eschar and surrounding erythema. Pseudomonas phospholipases are cytotoxic to endothelial cells (but not epithelial cells), so they cause vascular thrombosis.

Question 19

Pathogenesis of pseudomonas aeruginosa sepsis

Answer 19

Immunocompromised pt > invasion via gut or lung > perivascular nidus > invade vasculature > invade dermis and subcutaneous tissue > necrotizing vasculitis thrombosis > ecthyma gangrenosum

Question 20

Pseudomonas aeruginosa virulence factors

Answer 20

Exotoxin A, phospholipases, exoenzymes, proteases, hemolysins, siderophores. Also can grow on a variety of compounds like benzene, glycerol, ammonia, even distilled water. Multiple efflux pumps contribute to antibiotic resistance by exporting abx through inner and outer membranes.

Question 21

6. Explain why when Pseudomonas aeruginosa produces a toxin, which has the same mechanism of action intracellularly as diphtheria toxin does, then why don’t patients with Pseudomonas aeruginosa infections have the same symptoms as a patient with diphtheria.

Answer 21

Exotoxin A acts like Diphtheria toxin inside cells by inhibiting EF-2 and stopping protein synthesis. Expression is also regulated by iron, like diphtheria toxin. But, Exotoxin A has a different receptor. Diphtheria binds epidermal growth factor precursor. Exotoxin A binds alpha 2 macroglobulin receptor. Thus, the target cells and tissues are different. Diphteria only produces superficial infection while pseudomonas invades tissues and blood.

Question 22

4. Identify the predominant gram-negative organisms associated with opportunistic infections and discuss which one is most frequently found and which one is associated with the highest mortality.

Answer 22

Pseudomonas aeruginosa is associated with highest mortality. It is the most common pathogen isolated from patients who have been hospitalized longer than 1 week.

Question 23

Why doesn’t vaccination against Diphtheria (with diphtheria toxoid) protect against P. aeruginosa infections?

Answer 23

There is no immunological cross-reactivity between these toxins and virtually no primary amino acid sequence similarity hence, antibody against one will not neutralize the other.

Question 24

2. Describe the nature of a biofilm and identify one or more clinical conditions where biofilms play a role in a specific disease.

Answer 24

The genes that regulate protease production are also involved in a process called quorum sensing. This is a system that allows P. aeruginosa cells to communicate with each other through the production of compounds called homoserine lactones. These compounds are critical for P. aeruginosa and many other kinds of bacteria to form biofilms. Biofilms are formed in the lungs of CF patients.

Question 25

How do CF patients die

Answer 25

p. aeruginosa causes chronic inflammation (toxin induced) and possibly by immune complexes.

Question 26

What is unique about pseudomonas in CF patients

Answer 26

Contains Alginate, a compound that cuases the mucoid characteristics of pseudomonas infection in CF.