opportunistic infections Flashcards
- Define the terms Opportunistic, Nosocomial and Iatrogenic infections.
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.
Causes of granulocytopenia and resulting opportunistic pathogens
Low PMNS- Chemo or radiation. Gram negatives (e coli, pseudomonas aeruginosa, klebsiella pneumoniae) and staphylococcus
Causes of cellular immune dysfunction and resulting opportunistic pathogens
AIDS, age, smoking, T cell defects. Intracellular pathogens like salmonella, m. Tuberculosis and avium, listeria monocytogenes. Also VZV, CMV, HSV
Causes of humoral immune dysfunction and resulting opportunistic pathogens
Aggamaglobulinemia, splenectomy. Encapsulated pathogens like s. pneumoniae, H. flu and meningococci
opportunistic pathogens associated with foreign bodies
gram negatives, staphylococcus
opportunistic pathogens associated with surgery
staph, e coli and pseudomonas
iron and bacterial virulence
Excess Fe2+ is highly toxic due to the Haber-Weiss Fenton. Fe2+ catalyzes the production of hydroxyl-radicals. Bacteria also require iron for growth
Host defenses involving iron
- 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
Microbial mechanisms to scavenge iron from the host
- 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
Describe Acinetobacter baumannii infections
gram negative organism in the soils of Iraq. Causes infections of wounds, leading to sepsis. Risk factors include invasive procedures, wounds, hospitalization, antimicrobials
- 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.
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.
List bacteria with specialized capsules
P. aeruginosa, S. aureus, strains of oral Streptococci – enhanced colonization of damaged heart valve - endocarditis
List bacteria that produce urease
Proteus mirabilis, Staphylococcus saprophyticus, Klebsiella aerogenes, E. coli - associated with urinary tract infections (UTI) and kidney stones. H. pylori and stomach ulcers
Functions of endotoxin
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.
Types of pseudomonas aeruginosa infections and the predisposing conditions
- 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.
Issues relating to treatment of P. aeruginosa infections
High innate resistance mechanisms (many efflux pumps).Propensity to form biofilms
common sources of pseudomonas aeruginosa
whirlpools, swimming pools, hot tubs, loofah sponge
ecthyma gangrenosum
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.
Pathogenesis of pseudomonas aeruginosa sepsis
Immunocompromised pt > invasion via gut or lung > perivascular nidus > invade vasculature > invade dermis and subcutaneous tissue > necrotizing vasculitis thrombosis > ecthyma gangrenosum
Pseudomonas aeruginosa virulence factors
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.
- 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.
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.
- 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.
Pseudomonas aeruginosa is associated with highest mortality. It is the most common pathogen isolated from patients who have been hospitalized longer than 1 week.
Why doesn’t vaccination against Diphtheria (with diphtheria toxoid) protect against P. aeruginosa infections?
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.
- Describe the nature of a biofilm and identify one or more clinical conditions where biofilms play a role in a specific disease.
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.
How do CF patients die
p. aeruginosa causes chronic inflammation (toxin induced) and possibly by immune complexes.
What is unique about pseudomonas in CF patients
Contains Alginate, a compound that cuases the mucoid characteristics of pseudomonas infection in CF.
