lecture 18 Anaerobes Flashcards
What are the three classes of disease caused by clostridium?
- gas gang gangrene
- botulism
- tetanus
What are two enteric diseases caused by clostridium.
- food poisoning
- antibiotic-associated enterocolitis
What are the characteristics of clostridium?
-Anaerobic, gram-positive rods, form endospores, natural reservoirs -soil intestinal tracts and skin of humans and animals
What is the etiology Clostridial wound infections?
- usually mixed clostridial infection in wound following surgery or trauma.
- By Cl. perfringens, other cl. species
What is the etiology of gangrene?
Toxins caused by infection of clostridium spread to healthy muscle tissue and produce myonecrosis; by locally invasive organisms, Bacteremia is not common, but systemic toxemia can occur.
What is the pathogenesis of clostridium wound infections.
- α-toxin, acts on phospholipids and lecithin, causing cell lyses
- Θ-toxin, pore forming, lyses cell, toxic to heart and alters permeability of capillary
- No effective host defense in necrotic cells.
How are clostridial wound infections dx clinically?
- Clinical sx:
- -gas in tissues (crepitus), edema and shock in wound pain.
- -once a lesion appears, must begin treatment before lab results
How are clostridial wound infection dx in the lab?
-Mixed infection, one must be histotoxic (clostridium)
-Exudate smear - Gram positive rods with cellular infiltrate
-bacterial characteristics - “anaerobic growth”
double xone hemolysis (theta toxin)
check lecithinase activity on egg yolk
How are clostridial wound infection prevented/treated?
- surgical debridement and cleansing -antibiotics -Penicillin
- hyperberic O2
What is the source of clostridium in food?
- Meat prroducts
- spores germinate when food is heated
- enterotoxin is produces pores in enterocytes.
How is Cl. perfingens food poisoning dx clinically?
- onset 7-22 hours post ingestion
- diarrhea, cramps, abd pain, possible fever, nausea vomiting.
How is Cl food poisoning dx in the laboratory?
- non-motile (unlike other clostridia)
- spores sometimes seen on smears
Which genus of cl causes food poisoning?
Clostridium perfingens
How is Cl food poisoning treated?
- supportive therapy
- mortality near zero
What causes botulism?
-Clostridium botulinum
Where can Cl Botulinum be found?
-soil, silt, vegetation, intestinal tracts of humans and animals
What is classical botulism?
-is an intoxication, not an infection, caused by ingestion of preformed toxin in food contaminated with spores
What causes wound botulism?
usually infection of compound fracture, severe laceration or penetrating wound
What causes infant botulism?
caused by germination of spores in intestinal tract of infants; most cases in infants 2 weeks - 6 months; adults not affected by this syndrome
What causes inhalation botulism?
bioterrorism threat
What types of food are incriminated by Clostridium botulinum?
- improperly canned food
- fish preserved by salting or smoking
- prepared meats ingested uncooked
What is the action of the botulinum toxin?
- 7 distinct type inducing same disease
- absorbed in intestine, transported to neuromuscular junction.
- relatively toxic
- heat-labile
How is clostridium botulinum dx clinically?
- 12-96 hours, maybe 14 days
- GI sx- vomiting, constipation
- Nervous system- Flaccid paralysis
- mortality rate about 20% now declining
How is clostridium botulinum dx in a lab?
- isolation for organism form contaminated food or stool samples (oval, subterminal spores)
- Demonstration of toxin in food or patient serum or feces.
How is clostridium Botulinum treated?
-eliminate unabsorbed toxin; stomach lavage and
enemas
-eliminate source of toxin
-neutralize unbound toxin
-supportive care (especially respiratory support)
How is clostridium botulinum treated/prevented?
- antitoxin therapy (passive immunization)
- antibiotics of questionable value, except in cases of wound botulism
- Boil raw or fermented native dishes and home canned foods 10 minutes before eating
- Follow recommended home-canning procedures
What is the etiological agent of tetnus?
-Cl. tetani toxin, several antigen serotypes, but one toxin
What is the pathogenesis of Cl. Tetani?
- spastic paralysis following penetrating wound
- spores contaminate wounds
- germination, outgrowth and toxin production
- toxin enters motor neurons, transported to CNS by retrograde axonal transmission (travels along nerve fibers)
- highest mortality in elderly: >50% over 60 years
What is the action of the tetanus toxin?
- protein toxin is sole virulence factor
- Spastic paralysis: blocks inhibitory neurotransmitters
- very toxic like botulism
How is clostridium tetani dx clinically?
-initial sx- cramping and twitching of muscles around wound, then head and neck (lock jaw)
How is Cl Tetani dx in a lab?
- isolation of organism from wound
- spores
- demonstration of toxin neutralization with antitoxin
How is clostridium treated/prevented?
- maintenance of airway
- Benzodiazepines - -(GABA* agonists) tetanus immunoglobulin
- antibiotics to clear infectious focus
Does tetanus and botulinum toxins have the same enzymatic effect?
-They have the same effects, but in different neurons.
Tetanus attacks interneuron while botulism attacks the neuromuscular junction.
They both cleave the protein VAMP.
What causes abx-associated (pseudomembranous) colitis?
Clostridium difficile
What is the etiology of abx-associated colitis?
- follows antibiotic therapy; normal microbiota altered, spores germinate, overgrow, produce toxins and cause colitis; normal microbiota serve a protective role
- organism - normal microbiota, slender, gram positive rod with large, oval subterminal spores
What is the pathogenesis of Clostridium difficile?
- resistant to may abx
- two principal toxins cause disease by disrupting cytoskeletal elements of epithelial cells/submucosal tissue, A (enterotoxin) and B (cytotoxin) .
How does C. Difficile toxins work?
- large toxin
- 3 functional domains (receptor, membrane translocation, glucosyltransferase activity)
- once in cytoplasm, inactivate rho proteins by transferring glucose onto them.
What are some sx of C. Diff?
-abdominal pain; watery diarrhea, and mucus or blood
may be seen
-Mortality rate; 27-44% in untreated pts
How is C. Diff Dx?
- demonstration of pseudomembrane (sigmoidoscopy)
- fecal filtrates can be assayed for toxin
How is C. Diff treated?
-in most identified cases, symptoms resolve after
antibiotic therapy is discontinued
-Cl. difficile are usually susceptible to vancomycin and metronidazole
-relapse may occur following therapy Fecal Transplants
What made a C diff strain more virulent?
- More severe disease, increased complications,
high mortality rate, increased risk of relapse - Has mutation in regulatory gene – makes 16 to 24X as much toxin A&B
What are the characteristics of Bacteroides fragilis?
- Gram-negative rods; non-spore forming
- found primarily in the intestine; relatively O2 tolerant
- most frequently isolated anaerobe from diseased tissues; usually involved in diseases of the lower 1⁄2 of body
- bile resistant
What diseases are caused by Bacteroides Fragilis?
- intra abd abscess
- Skin and soft tissue infections
- secretory diarrhea in children
What are sx of intra abdominal abscesses?
- localized infections following compromise of the integrity of the intestine
- low grade fever abdominal pain
- can lead to bacteremia with high morality rate
What are some sx of skin and soft tissue infections?
- cellulitis, fasciitis associated with surgical wound infections
- infections of diabetic and decubitus ulcers
What is the pathogenesis of bacteroides fragilis?
- capsular polysaccharides, forms abscess
- mixed infections
- penicillin resistant
How is bacteroides fragilis dx?
- abscesses, Radiologic CT and or aspiration
- gram stain culture
How is bacteroides fragilis treated?
- abx, use a couple in case is polymicrobial
- drainage of abcess
