SPORE FORMING GRAM POSITIVE RODS: Clostridia (anaerobes): C. Perfringens, C. Tetani, C. Bolulinum, C.

Difficile

CLOSTRIDIUM TETANI
CHARACTERISTICS
- Large gram + rods, anaerobic
- Form terminal endospores (tennis racket-like)
- Habitat in soil
- Enter via traumatic breaks in skin
o Nail breaks skin, skin popping (drug injections), human bites
- Endospore germination favour by:
o Necrotic tissue (low tissue oxygenation)
o Poor blood supply to wound
- Neonatal tetanus:
o Organisms enters via contaminated umbilicus or circumcision wound) is problem in developing countries

PATHOGENESIS
- Tetanus toxin (tetanospasmin)
o Exotoxin, polypeptide, produced by clostridium tetani at wound site
- Travels intra-axonally
o to CNS & binds to Ganglioside receptors.
- Cleaves proteins involved in release of inhibitory neurotransmitters
o Blocks release of GABA and Glycine at Spinal synapses
o Excitatory neurons are unopposed and extreme muscle spasm results.

CLINICAL FINDINGS
- Strong muscle spasms due to the unopposed excitatory neurons - spastic paralysis (tetany).
- Specific features:
o Lockjaw (Trismus) rigid contraction of jaw muscle, preventing mouth from opening;
o Risus sardonicus due to spasm of facial muscles
o Exaggerated reflexes
o Opisthotonos A state of severe hyperextension and spasticity (Tetanic spasm)
spine and extremities are bent with convexity forward
spasm of extensor muscles is common
the body resting on the head and the heels
- Respiratory failure ensues.
- High mortality rate.

LAB DIAGNOSIS AND TREATMENT

Lab diagnosis:
- Diagnosis primarily clinical no microbiologic or serologic diagnosis
- Organism is rarely isolated
Treatment:
- Treated w/ hyper-immune human globulin (TIG) to neutralize toxin
- Wound debridement
- Penicillin G or metronidazole
- Airway must be maintained and respiratory support might be required
- Muscle relaxants (spasmolytic drugs) eg. benzodiazepine

PREVENTION
- Toxoid vaccine (formaldehyde inactivated toxin)
o Given to children in combination w/ diphtheria toxoid and pertussis vaccine
- Toxoid booster administered every 10 years
 SPORE FORMING GRAM POSITIVE RODS: Clostridia (anaerobes): C. Perfringens, C. Tetani, C. Bolulinum, C. Difficile
- Patients w/ trauma treated w/ toxoid booster and debridement of wound + immune globulin for patients for not
previously vaccinated
- In cases of gross contamination of wound, tetanus immune globulin and prophylactic penicillin treatment can
be used
CLOSTRIDIUM BOTULINUM
CHARACTERISTICS
- Causes botulism
- Anaerobic, Gram +, endospore forming rods
- Habitat is soil
o Endospores widespread in soil, commonly in contaminated vegetables and meat as well
- Transmitted in improperly preserved food:
o Inadequate sterilization of canned/vacuum-packed food spores NOT killed
o Spores can germinate, multiply and produce toxins in anaerobic environment
o Preformed toxin ingested
- Highest risk foods:
o Alkaline vegetables (green beans, peppers, mushrooms), smoked fish
o Toxin can be inactivated by boiling for several minutes

PATHOGENESIS
- Botulinum toxin (A-B Polypeptide neurotoxin)
o Absorbed from gut and carried via blood to peripheral nerve synapses
- Heat labile (unlike staph), 10 minutes 60C
- Toxin is protease that cleaves proteins involved in release of acetylcholine at myoneural jxn
o Blocks release of acetyl choline
o Causes reversible flaccid paralysis
- 8 immunologic types of toxins viz A, B, E are most common

CLINICAL FINDINGS
Clinical forms:
- Adult botulism due to preformed toxin ingestion via canned food/ smoked fish
o Descending weakness and flaccid paralysis, including diplopia, dysphagia and respiratory failure
o Diarrhea, nausea, vomiting
o Fever absent
- Wound botulism
o Spores contaminate wound and germinate, producing toxin at site of infection (traumatic implantation
of spores)
- Infant Botulism (Floppy Baby Syndrome)
o Due to ingestion of spores from household dust, honey
o C. Botulism grows in gut and produces toxin
o Ingestion of contaminated honey most likely to cause it
o Infants develop weakness or paralysis, but usually recover spontaneously
Constipation may be present
MORE STUFF
Lab Diagnosis:
- Organism not usually cultured
- Presence of toxin in serum, stool
Treatment:
- Trivalent antitoxin to toxin serotypes: A,B,E
- Resp. support may be required
Prevention
- Correct food-preservation, cooking all home-canned presrves, NO HONEY FOR INFANTS TILL 1 YR OLD
- Throw away bulging cans: they buldge b/c of clostridium proteolytic enzymes
 SPORE FORMING GRAM POSITIVE RODS: Clostridia (anaerobes): C. Perfringens, C. Tetani, C. Bolulinum, C. Difficile
CLOSTRIDIUM PERFRINGENS (OR) CLOSTRIDIUM WELCHII
CHARACTERISTICS
- Anaerobic, gram positive, spore forming rod (duh)
- Stormy fermentation in milk media (litmus milk test)
- Double zone of beta hemolysis
- Non motile
- Habitat: soil (endospore widespread) as well as
o human colon and vagina
(vegetative cells part of normal flora)

TRANSMISSION AND DISEASE

- Food borne, traumatic implantation
- Causes 2 diseases:
o Gas gangrene (myonecrosis)
o Food poisoning
- Gas gangrene:
o Results from contamination of wound w/
Soil/feces
o War wounds/car crash/ septic abortion
- Food poisoning:
o Results from ingestion of contaminated food
o Endospores survive cooking and multiply
In reheated meat dishes
o Enterotoxin self-limiting, non-inflammatory, watery diarrhea

gas gangrene continued

- Bacterium grows in traumatized tissue, especially muscle, at low 02 tension
- Produces several cytotoxic factors, ESPECIALLY:
o LECITHINASE (alpha toxin/ phospholipase C) that cleaves cell membranes, damage RBCs, platelets,
WBCs, endothelial cells results in massive hemolysis, tissue destruction and hepatic toxicity
o Degradative enzymes: generate gas in tissue (eg. h2 and co2)

- Clinical findings:
o Acute pain, edema, cellulitis occur in wounded area
o Crepitation (tense tissues) indicates gas w/I tissue
o Hemolysis, jaundice, blood-tinged exudates are common
o Systemic symp. Include: fever, tachycardia, diaphoresis, pallor
o Shock and death may ensue HIGH MORTALITY RATE
- Gas gangrene can occur in patients following amputation (poor sanitation)

- large gram + rods

- Anaerobic culture
- Double hemolysis on blood agar
- Nagler reaction (lecithinase test)
o Egg yolk agar plate is used to demonstrate
Lecithinase (phospholipase C) activity
ID of alpha-toxin of C.perfringens
Addition of antitoxin to culture of egg yolk
Prevents visible opacity, due to lecithinase
Axn which normally observed in colonies
 SPORE FORMING GRAM POSITIVE RODS: Clostridia (anaerobes): C. Perfringens, C. Tetani, C. Bolulinum, C. Difficile
TREATMENT
- Wound debridement
- Administration of penicillin G, clindamycin
- Hyperbaric O2 chamber

PREVENTION
- Wounds should be cleaned and debrided
- Prophylaxis w/ penicillin can be used
- NO VACCINE!

FOOD POISONING
PATHOGENESIS AND CLINICAL FINDINGS
- Mainly acquired by consumption of infected reheated meat dishes
- Enterotoxin w/I gut S. Aureus enterotoxin, in comparison, acts via disrupting ion transport
- Incubation period is 8-16 hours (like bacillus cereus diarrheal toxin)
- Disease characterized by watery diarrhea w/ cramps and little vomiting
- Self-limiting resolves within 24 hours

TREATMENT: Symptomatic treatment is given; no antibiotics administered

PREVENTION: No specific preventative measures; adequate cooking needed to kill organism in food

CLOSTRIDIUM DIFFICILE
CHARACTERISTICS
- Anaerobic, gram +ve, spore forming rods
- Habitat is human colon; carried in GI tract of about 3% of general popn
o 30% of hospitalized patients on antibiotics
- Causes antibiotic-associated pseudo-membranous colitis
o Most common nosocomial cause of diarrhea
- Transmission is: FECAL-ORAL and Hospital personnel are v. important vectors

PATHOGENESIS
- Ab therapy leads to suppression of drug-sensitive species w/I normal intestinal flora:
o Clindamycin was first drug implicated
o Others: cephalosporins (2rd, 3rd gen ceftriaxone most common), amoxicillin, ampicillin
o Cancer chemotherapy also predisposes to pseudomembranous colitis
- Allows overgrowth of C. Difficile w/I intestine: rarely invades intestinal mucosa
- Produces large quantities of EXOTOXINS A AND B
o TOXIN A: enterotoxin damages mucosa leading to fluid increase, granulocyte attractant
o TOXIN B: cytotoxin cytopathic
DISRUPTION OF COLONIC MICROFLORA
CLINICAL FINDINGS
- Diarrhea, colitis which is usually non-bloody C. DIFFICILE EXPOSURE AND COLONIZATION
- Neutrophils present in stools in of the cases
- Abdominal cramping and fever RELEASE OF TOXINS A and B
- Pseudo membranes:
o Thick yellow/ white plaques formed on colonic mucosa MUCOSAL INJURY AND INFLAMMATION
o Can by be visualized w/ sigmoidoscopy
- Toxic megacolon
o Abd. Pain, bloating, tenderness, fever, tachycardia, septic shock, colonic dilation on abd. X-ray, requires
surgical resection on the colon
 SPORE FORMING GRAM POSITIVE RODS: Clostridia (anaerobes): C. Perfringens, C. Tetani, C. Bolulinum, C. Difficile
LABORATORY DIAGNOSIS
Stool exam for toxin production
- CI. Difficile screen by ELISA or cyto test
- Culture not useful as its part of normal flora

TREATMENT
- w/I causative antibiotic (mild disease)
- oral metronidazole (severe diseases)
- vancomycin effective BUT should be avoided where
possible due to risk of selecting for vancomycin
resistant normal flora

PREVENTION
- no vaccine or prophylactic drugs are available
- cautious use of broad spectrum antibiotics
(limited spectrum drugs should be considered first)

Patients in nursing home need to be isolated and bed pans need to be

Autoclaved to kill spores