Opportunistic Infections Flashcards
Opportunistic Infection
infection occurs in compromised host by organism that does not usually infect a normal host. Diminution in host defense opens the door to invasion/disease, which seems to be true whether bug is classic pathogen or member of own normal flora with low virulence normally.
Example: classic pathogens like cholera and TB are opportunists since they more often cause overt dz in weakened ppl
Nosocomial infection
those occurring in institutional setting (hospital, convalescent centers, nursing homes)
Iatrogenic infection
infection due to activity of physician or other health care giver. Term doesn’t necessarily imply culpability.
Factors predisposing for infection
- Granulocytopenia (chemo/radiation)
- Cellular immune dysfunction (AIDS)
- Humoral immune dysfunction
- Obstruction phenomenon
- CNS dysfunction
- Iatrogenic procedures
Sources of potential pathogens
- Air ( air conditioning; Aspergillus)
- Water (sinks/showers- P. aeruginosa, S. marcescens, L. pheumophilia)
- Direct contact (S. aureus)
- Food (G -ve bacilli)
- Endogenous (nl flora–E.coli/ Pseudomonas, S. aureas)
- Environmental presence (Iraqibacter–acinetobacter baumannii originally from Iraqi sand but now in US nosocomial settings)
- Other (foreign body, burns increases susceptibility)
bacterial Factors contributing to opportunistic infection
- toxins/virulence factors
- specialized factors (attachment to certain sites, capsules, metabolic factors- urease)
- Endotoxin & Septic shock
Endotoxin and Septic Shock
- LPS (lipopolysaccharide) or LOS (lipo-oligosaccharides) in al gram negative organisms contribute to septic shock
- Not extremely toxic by itself but need particular host response to set off cascade
- humans particularly sensitive to endotoxin; smalldoses can stimulate immune system but large doses sets off cascade, with macrophage as primary effector cell
- Macrophage is overstimulated –releases TNF, which in turn causes it to release cytokines (IL-)
- Endothelial cells appear to be target for cytokines and the effector cell once sepsis started
- once organs affected, mortality >50%
** Can bleb off organism into system
Nutritional immunity
ability of host to withhold trace nutrients scavenged by pathogens
- Iron, Phosphate, Magnesium
- for example we shunt Fe into storage rather than plasma when invaded by microorganisms and decrease our intestinal absorption
- states of hyperferremia/hypotransferrinemia observed to underlie increased susceptibility of humans to infection
Which bug is associated with highest mortality in opportunistic infections
P. aeruginosa
- most common pathogen isolated from pts hospitalized > 1 week
- can grow in distilled water, quaternary ammonium disinfectants sometimes used in hospitals/other places
What makes P. aeruginosa so bad
- Metabolic diversity (metabolize benzene or use simple compounds like glycerol/ammonia)
- Produces secondary metabolites–some hae antibiotic activity, some toxic to epithelial cells, some Fe-chelating to get Fe from host
- Antibiotic resistance – chromosome mediated EFFLUX PUMPS (>25) and inducible beta lactamase when those antibiotics present
- ability to develop resistance to even newest antibiotics after only single course of therapy (3rd/4th gen Cephalosporins)
Virulence factors of Pseudomonas aeruginosa
- produces toxinc factors contributing but not required
- some factors important in one kind of infection but not so much in another
1) Exotoxin A (ADP-ribosyl transferase inhibits EF-2 to stop protein synthesis; similar to diphtheria oxin)
2) Multiple Phospholipases: One substrate product = precursors to inflammatory mediators/signaling molecules. Other product protects bug against osmotic pressure in certain infections (CF lung)
3) Proteases–invasion and destruction of Fe binding proteins; genes for these also involved in biofilm formation
Ecthyma Gangrenosum
- Pathognomonic of sepsis caused by P. aeruginosa
- gun-metal gray, infarcted lesion with surrounding erythema that evolves into necrotic black or gray-black eschar and surrounding erythemia
- probably due to phospholipase that is highly cytotoxic to ENDOTHELIAL but not epithelial cells and causes vascular thrombosis
Diseases caused by P. aeruginosa
**can infect almost any body site
- Burn wound – more concerning in developing countries
- Septicemia - Cancer pts, premature infants, AIDS, immunosuppressed
- UTI- indwelling catheters
- Ophthalmic infection
- Skin (hot tubs, loofa–dermatitis/folliculitis; can occur in healthy ppl but not serious)
- Wound infections in diabetics (often co-infected with S. aureus–slow to heal/hard to treat)
- Pulmonary acuteinfection (elderly w/emphysema; nosocomial pneumonias)
- Pulmonary chronic infectino - Cystic fibrosis
Pathogenesis of P. aeruginosa in CF
- once P. aeruginosa infects CF pt, it is hard to eradicate even with powerful antibiotics
- mainly in bronchiolar spaces but damages lungs, likely from chronic inflammation due to toxins/possibly immune complexes
- eventually most CG pts will die from damage
Cystic Fibrosis
- most common fatal, homozygous recessive disorder in Caucasians
- CF gene encodes protein CFTR that acts as chloride channel and channel regulator
- mutations give range of sxs, so range of dz
- pts have increased susceptibility to H. flu, S. aureus, P. aeruginosa infections since they can’t clear infections with viscus/dehydrated mucus
