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General information about Clostridia (gram, shape, aeration, major species w/ disease)
- Gram+
- Rods
- Anaerobic
- C. perfringens: histotoxic (tissue destructive) infections (myonecrosis). Food poisoning.
- C. botulinum: botulism (flaccid paralysis)
- C. tetani: tetanus (spastic paralysis)
- C. difficile: pseudomembranous colitis
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What makes Clostridia anaerobic (physiology)?
- Cannot use free oxygen as terminal electron acceptor (use small organic molecules instead)
- Inhibited/damaged by O2 due to lack of peroxidase, catalase, and superoxide dismutase enzymes
- Must be grown on media in presence of reducing agent OR O2 free environment
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General information about C. perfringes (shape, motility, gram, capsule, found where, potential disease states?)
- Large rod
- nonmotile
- gram positive
- encapsulated
- Ubiquitous in nature. Spores in soil, normal flora in vagina and GI.
- Causes gas gangrene (myonecrosis) when introduced into tissues
- Some strains causes food poisoning (very common in US)
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Virulence factors in C. perfringes
- Exotoxins: 12 exotoxins (α is most important, lyses membranes)
- grouped A through E based on exotoxins
- Enterotoxin: causes loss of fluid and intracellular proteins in small intestine.
- Degadative enzymes: proteases, DNases, hyaluronidase, collagenases help to promote spread of infection
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Describe the disease states caused by C. perfringens (more detailed)
- Myonecrosis (gas gangrene): clostridial spores introduced into tissue
- exotoxins and degredative enzyme cause tissue necrosis and quick spread of bacteria
- Fermentation of tissue carbohydrates yields gas which accumulates in subcutaneous spaces
- Untreated myonecrosis is fatal within days
- Food poisoning: most common cause of food poisoning in US
- nausea, abdominal cramps, and diarrhea (no fever or vomiting)
- Self-limiting
- Requires very large inoculum (10^8 organisms)
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Lab ID of C. perfringens
- gram stain reveals vegetative clostridial forms
- Double zone of hemolysis on blood agar
- Sought in feces of food poisoning cases
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Describe the diseases caused by C. botulinum w/ mechanism
- mechanism: caused by botulinum toxin
- Cleaves synaptic vesicle peptides
- Prevents transmission of aceytlcholine, resulting in inability to contract muscle
- Classic Boltulism (flaccid paralysis): food poisoning w/o fever or sepsis
- Patient may die from respiratory paralysis
- Infant botulism: most common
- Colonizes large bowel of infants and toxin is slowly absorbed
- May be in honey supplements
- Wound botulism: rare form of botulism when toxin is absorbed from colonized wound
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Describe the epidemiology of C. botulinum (found where, infection occurs how)
- In soil, aquatic sediments - contaminate vegetables, meat, fish
- Toxin is produced during vegetative growth
- Toxin often elaborated in food (organism not required for botulism)
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Treatment of C. botulinum
- Antitoxin which neutralizes botulinum toxin ASAP (horse antiserum)
- Penicillin for would botulism (doesn't affect toxin)
- Toxin is destroyed at boiling temperatures, but spores require autoclaving
- Immunity DOES NOT occur
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Describe the epidemiology of C. tetani (where found, typical infection route)
- Common in barnyard and garden soils
- Typical infection is puncture wound (eg nail, splinter) that allows spores to germinate
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Describe the disease caused by C. tetani w/ mechanism
- Mechanism: Tetanus toxin (tetanospasmin) transported from infected locus by retrograde neuronal flow
- Prevents release of glycine, resulting in constant contraction
- Tetanus (spastic paralysis): early stage presents lockjaw, then more muscles become involved.
- Death caused by paralysis of chest muscles leading to respiratory failure
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Describe the treatment of C. tetani
- Prompt administration of antitoxin (before confirmation) to neutralize unbound toxin
- Human tetanus Ig preferred, but horse antitoxin can be used
- Organism sensitive to penicillin
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Describe the prevention of C. tetani
- Active immunization (DPT aka TDAP)
- Boosters are required every 10 years
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General information about C. difficile (range of outcomes, amount of infection, how frequent is disease)
- Can range from loose stools to life-threatening pseudomembranous colitis (PMC)
- Responsible for 1/4 of antibiotic-associated diarrheas
- Kills 3 times as many people as MRSA in US
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Describe the epidemiology of C. difficile
- Minor component of normal flora
- Antibiotic treatement suppresses more predominant species, C. difficile proliferates
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What are the virulence factors for C. difficile?
- Toxin A: enterotoxin that causes excessive fluid secretion, stimulates inflammatory response
- Toxin B: cytotoxin that disrupts protein synthesis and disorganizes cytoskeleton
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Describe the Lab ID of C. difficile
best tests demonstrate toxin production in stool extracts (ELISA for exotoxins A and B)
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Describe the treatment for C. difficile
- Discontinuance of predisposing drug
- Fluid replacement
- Relapses are common.
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