Opportunistic Infections

Question 1

Definitions:

opportunistic

nosocomial

iatrogenic

Answer 1

Opportunistic infections: infections caused by organisms that do not normally cause disease in healthy or immunocompetent individuals.

Nosocomial infections: infections that occur in an institutional healthcare setting.

Iatrogenic infections: infections originating directly from something that health care workers do.

Question 2

Importance/characterstics of biofilms

Answer 2

• Biofilm = polysaccharide goo secreted by various organisms
• Catheters, in particular, seem to attract things that like to secrete biofilms such as S. epidermidis.
• Pseudomonas biofilms like to stick to mucus in the lungs of CF patients, catheters, drains of hot tubs, etc.
  
  • Pseudomonas secretes alginate to combine with the mucus in CF lungs to form a kind of jelly.
  • The PMNs can’t get to the bugs through the biofilm.

Question 3

Conditions that increase risk for opportunistic infections

Answer 3

• granulocytopenia
• T-cell dysfxn
• humoral immunity dysfxn
• presence of foreign body
• surgery

Question 4

Common infections in granulocytopenia

Answer 4

• → skin and respiratory infections with Gram-negatives and Staph species
• # 1 risk factor for P. aerinogenosa
• Due to chemo, radiation therapy, burns

Question 5

Common infections in t-cell dysfxn

Answer 5

→ get intracellular pathogens like Salmonella, TB, Listeria, Legionella, Shingles reactivation

HIV/AIDS

Immunosuppression

Question 6

Common infections in humoral immunity dysfxn

Answer 6

• → susceptible to encapsulated pathogens like S. pneumoniae
• Splenectomy
• Gammaglobinemia

Question 7

Common infections in presence of foreign body or surgery

Answer 7

• Presence of a foreign body, great for biofilms → Gram-negatives and Staph species
  
  • Central line
  • Endoscope, Bronchoscope
  • Urinary catheter
• Surgery → Staph, E. coli, Pseudomonas

Question 8

Common gram-negatice organisms associated w/opportunistic infections

Answer 8

• E. coli is probably the most common
• Pseudomonas
  
  • Pseudomonas = highest mortality rate (on average, 40-50%)
  • Strongly associated with cystic fibrosis
  • Also associated with burn infections, puncture wounds, hot tubs, etc.
  • P. aeruginosa lives in moist soil; so puncture wounds from stepping on nails, etc in the dirt are often associated with it.

Question 10

Cellular component that contributes to the pathogenesis of extraintestinal gram-negative infectiosn

Answer 10

• Endotoxin/”LPS” = @ cell walls of Gram (-).
  
  • contains Lipid A = pathogenic portion ==> released when the bacterium is lysed
• Lipid A activates macrophages, which release IL-1 and TNF-α (a pyrogen and a vasodilator, respectively) ==> fever and septic shock.
• Endotoxin can also cause DIC, largely through the same pro-coagulant mechanisms.

Question 11

Evidence that demonstrates endotoxin pathogenicity

Answer 11

1) similarity in clinical manifestations between infection and administration of LPS to man or animals.
2) common pattern of hematologic changes following LPS administration and infection.
3) generation of kinins and activation of Hageman factor in clinical infection and following LPS administration to animals.
4) Consumption of complement
5) antibody against core glycolipid antigens of LPS protects man and experimental animals against sequelae of shock.

Question 12

Pseudomonas vs. Diptheria toxin

Answer 12

• Pseudomonase Exotoxin A prevents protein synthesis = same MOA as diptheria
• The delivery mechanism interacts with different receptors and has slightly different antigenicity. (e.g. ETEC and Cholera toxins)
• Cornyebacterium diphtheriae only invades superficial tissue in the pharynx and skin;
• Pseudomonas gets into the blood and deep tissues.

Question 13

Diptheria vs. Pseudomonas toxin receptor

Answer 13

• diptheria toxin receptor = epidermal growth factor precursor.
• Exotoxin A receptor = a2 macroglobulin receptor.

Question 14

Major virulence factors of Pseudomonas

Answer 14

• High innate resistance through lots of efflux pumps to get rid of antibiotics, and
• Tends to form biofilms ==> attach to mucus in lungs
• Some strains have an antiphagocytic capsule that helps it adhere to target cells
• Other virulence factors:
  
  • Endotoxin/Lipid A
  • Phospholipases, proteases.

Question 15

Host mechanisms to limit free iron

Answer 15

• Nearly all bacteria require iron for growth (except lactobacilli and Treponema).
• iron in the plasma is bound to transferrin or lactoferrin ==> deny free iron to microorganisms and avoid creating free radicals from the hyperferremia.
• @ invasion by microorganisms, iron ==> storage @ hemosiderin laden macrophages.
• decrease absorption from the gut as well.

Question 16

Mechanism used by microorganisms to overcome limited iron access

Answer 16

• proteins with high affinity for iron (siderophores), to wrest it away from the binding proteins.
• either synthesize products to take iron out of transferrin/lactoferrin or just absorb lactoferrin whole and degrade it apart.
• Toxins that destroy cells also release lots of iron.

Question 17

Factors that upset balance of limiting nutrients @ host ==> disease by opportunistic infections

Answer 17

If you give people, particularly kids, lots of iron, they have a higher incidence of disease, for example, in constant transfusions in sickle cell or β-thalassemia.