Clostridia Flashcards
Clostridia overview
Obligate anaerobes
- catalase negative, oxidase negative
- collect sample in thioglycolate (reducing agent), avoid open swabs, grow with gas pack to reduce O2
Gram + bacilli
Form spores - location -> identification (terminal = tetani)
C botulinum - non-invasive, botulism toxin -> flaccid paralysis
C tetani - generally non-invasive, tetanus toxin -> tetani
C difficile - non-invasive, secreted exotoxins (A,B) -> pseudomembranous diarrhea
C perfringens - very invasive -> gas gangrene
Alpha toxin = lecithinase - lyses host cell membranes
Culture - lactose-egg yolks
-> C perfringens -> white (phospholipase), red (lactose ferment)
-> C botulinum -> oily (lipase), clearing around (protease)
Major disease mechanisms
Toxin-mediated
- pre-formed exotoxin - live bacteria not necessary
- Clostridia botulinum -> clostridia toxin
- Staphylococcus aureus -> enterotoxin (most common food -> diarrhea in US)
- ingestion -> adherence, growth and secretion in gut
- infant botulism (honey -> anaerobic gut)
- Vibrio cholerae
Invasion and immune/inflammatory
- Clostridium perfringens
2.
Clostridium tetani pathogenesis
Gram + rod - terminal spore is diagnostic (“tennis racket”)
- motile (flagella)
Non-invasive
Anaerobic -> spores germinate (4d-weeks incubation)
Tetanus toxin - two subunits (A, B) - formed via protease
-> peripheral and ventral horn nerves
- B - binds to neuronal gangliosides
- A - disables neurotransmitter release (glycine, GABA) ->
Spastic paralysis, flexors predominate, symmetrical
-> dysphagia, respiratory failure, secondary infections, autonomic, cardiac (60% mortality)
- no fever, no sensory deficit (intense pain)
Tetanus epidemiology
Common in soil
Rare disease in developed due to vaccination
Developing - infected umbilical stump, deep/dirty wounds
Vaccine = toxoid (formaldehyde-inactivated toxin)
- x3 in first 6 mos -> booster at 1 y, 6 y, every 10 y
- part of DTP, TDaP
Tetanus clinical
Dx: largely via presentation
- rarely observe organisms (precedes sx), 39% culture positive
Tx: - wound debridement - penicillin (alt: metronidazole) - respiratory, supportive Within 5 y -> no further tx Between 5-10 -> toxoid booster >10 years -> toxoid booster (+ human IgG if dirty wound) Not vaccinated -> full course (x3) (+ human IgG if dirty wound)
Clostridium botulinum overview
Gram + rod, subterminal spore (not diagnostic)
- spore - resistant to heat, drying, etc
- > grow in anaerobic (veggies, smoked fish, fruit) -> 2-3d
- > toxin = heat-labile (cook your canned food! 100C x 10 min)
(infant and wound botulism require germination and growth within host)
Clostridium botulinum pathogenesis
Toxin - very potent, heat-labile but resistant to stomach acid
- 7 types - A, B, E are most common
- 2 subunits (B - binding, A - action)
GI -> blood -> peripheral nerves -> synaptic receptors -> entry
-> blocks Ach proteolytic processing
-> flaccid paralysis (descending), includes CN’s and PNS, symmetrical
(dysphagia, dry throat, diplopia, dilated pupils)
-> respiratory (12% fatality)
- no sensory deficit, no fever, normal mentation
Incubation 18-36 h
Effect is irreversible after binding to synapse (recovery via regeneration)
Botulism clinical
Dx: clinical - do not rely on culture (toxin mechanism)
- can detect toxin in stool, blood, vomit, food
- electromyoygraphy (EMG) -> decreased AP’s in nerves (suggestive, not diagnostic)
- differential = myasthenia gravis, Guillain-Barre (ascending)
Tx:
- removal, gastric lavage
- horse antitoxin - toxin specific (A, B, E)
- supportive, respiratory
Infant botulism
1-8 months (normal microbiome not established)
Food (honey) -> germination/proliferation in gut -> toxin
Clinically more subtle - constipation, weak neck/trunk, CN deficits
Confirm via toxin or organism in blood, stool, food (A,B,F common)
Tx: supportive, new human antitoxins (A,B) vs allergies to horse
Wound botulism
Soil contamination -> germination -> toxin
Incubation 4-14 d
Dx via wound culture, toxins in serum
Tx - antitoxin, supportive
Clostridium difficile overview
Anaerobic Gram + rod, spores resistant to degradation
Colonizer - 3% overal, 30% of hospitalized (via fecal-oral)
- is hand-washing enough to prevent spore transmission?
- contact isolation if found
- serotype antigens - ex flagella
- O27 strain (Canada, England) - more virulent, more toxin released, resistant to fluoroquinolones
Antibiotics (ampicillin, cephalosporins, clindamycin, fluoroquinolones) -> disrupt normal flora -> allows proliferation and toxin release
- prevent by not overusing antibiotics
- tx by stopping antibiotics that caused it…
C difficile pathogenesis
Suppression of normal flora -> proliferation -> toxins
Exotoxin A - enterotoxin vs gut receptors
Exotoxin B -> ADP ribosylation of Rho (GTP-binding protein) ->
cytotoxic to mucosa
-> pseudomembranes, diarrhea (sometimes bloody), fever
Dx:
- hx of antibiotics (ampicillin, cephalosporin, clindmycin)
- stool -> WBC’s, live bacteria
- toxins via bioassay, lateral flow assay, ELISA
- pseudomembranes on sigmoid/colonoscopy
Tx
- stop antibiotics
- metronidazole, vancomycin, fidaxomicin
- fecal transplants?!
Clostridium perfringens overview
Anaerobic Gram + rod, non-motile
Present in soil, GI, vagina
Histotoxic, invasive -> rapidly progressing gangrene, necrosis
- similar organisms: septicum, bifermentans, ramosum
Also food poisoning from pre-formed toxin
Culture -
- clearing on milk plate (lecithinase), blood (double zone - alpha, theta)
- “boxcar” shape
Gas gangrene pathogenesis
C perfringans or similar organism
Multiple toxins -> tissue necrosis
- lecithinase -> membranes (host capillaries and RBCs)
- collagenase, hyaluronidase (ECM)
Grow rapidly in anaerobic (ex surgical wound)
-> gas from fermentation (H2, CO2), also acids, proteases
Depends on location - can occur without open wound
- cellulitis (superficial or necrotizing dermis, capillaries)
- fasciatis +/- necrosis
- myositis, myonecrosis (muscle)
- can lead to bacteremia
- uterine, septic abortion (rare)
- GI lesion (rare, 2t leukemia, lymphoma)
Gas gangrene clinical
Dx: - crepitus from subq gas - edema, severe pain - discoloration, dark serous exudate - Gram stain, anaerobic culture of wound - imaging -> air in the wrong spot Tx: fatal if not treated promptly - surgical, wound debridement (increase tissue O2) - penicillin - hyperbaric O2?
