GRAM-POSITIVE BACILLI – ANAEROBIC SPORE-FORMING

1. Clostridium tetani
Disease—Tetanus. Characteristics—Anaerobic, gram-positive, spore-forming rods. Spore is at one end (“terminal spore”),
so organism looks like a tennis racket. Habitat and Transmission—Habitat is the soil. Organism enters through traumatic
breaks in the skin.
Pathogenesis—Spores germinate under anaerobic conditions in the wound. Organism produces exotoxin, which blocks
release of inhibitory neurotransmitters (glycine and γ-aminobutyric acid [GABA]) from spinal neurons. Excitatory neurons
are unopposed, and extreme muscle spasm (tetanus, spastic paralysis) results.
“Lock-jaw” and “risus sardonicus” are two examples of the muscle spasms. Tetanus toxin (tetanospasmin) is a protease
that cleaves proteins involved in the release of neurotransmitters.
Laboratory Diagnosis—Primarily a clinical diagnosis. Organism is rarely isolated. Serologic tests not useful.
Treatment—Hyperimmune human globulin to neutralize toxin. Also penicillin G and spasmolytic drugs (e.g., Valium). No
significant resistance to penicillin.
Prevention— Debride wound. Toxoid vaccine (toxoid is formaldehyde-treated toxin). Usually given to children in
combination with diphtheria toxoid and acellular pertussis vaccine (DTaP). If patient is injured and has not been
immunized, give hyperimmune globulin plus toxoid (passive–active immunization). Give tetanus toxoid booster every 10
years.
2. Clostridium botulinum
Disease—Botulism. Characteristics—Anaerobic, gram-positive, spore-forming rods.
Habitat and Transmission—Habitat is the soil. Organism and botulinum toxin transmitted in improperly preserved food.
Pathogenesis—Botulinum toxin is a protease that cleaves proteins involved in the release of acetylcholine at the
myoneural junction, causing flaccid paralysis. Failure to sterilize food during preservation allows spores to survive. Spores
germinate in anaerobic environment and produce toxin. The toxin is heat-labile; therefore, foods eaten without proper
cooking are usually implicated.
Laboratory Diagnosis—Presence of toxin in patient’s serum or stool or in food. Detection of toxin involves either
antitoxin in serologic tests or production of the disease in mice. Serologic tests for antibody in the patient are not useful.
Treatment—Antitoxin to types A, B, and E made in horses. Respiratory support may be required. Prevention—Observing
proper food preservation techniques, cooking all home-canned food, and discarding bulging cans.
3. Clostridium perfringens
Diseases—Gas gangrene (myonecrosis) and food poisoning.
Characteristics—Anaerobic, gram-positive, spore-forming rods.
Habitat and Transmission—Habitat is soil and human colon. Myonecrosis results from contamination of wound with soil
or feces. Food poisoning is transmitted by ingestion of contaminated food.
Pathogenesis—Gas gangrene in wounds is caused by germination of spores under anaerobic conditions and the
production of several cytotoxic factors, especially alpha toxin, a lecithinase that cleaves cell membranes. Gas in tissue
(CO2 and H2) is produced by organism’s anaerobic metabolism. Food poisoning is caused by production of enterotoxin
within the gut. Enterotoxin acts as a superantigen, similar to that of S. aureus.
Laboratory Diagnosis—Gram-stained smear plus anaerobic culture. Spores not usually seen in clinical specimens; the
organism is growing, and nutrients are not restricted. Production of lecithinase is detected on egg yolk agar and
identified by enzyme inhibition with specific antiserum. Serologic tests not useful.
Treatment—Penicillin G plus debridement of the wound in gas gangrene (no significant resistance to penicillin). Only
symptomatic treatment needed in food poisoning.
Prevention—Extensive debridement of the wound plus administration of penicillin decreases probability of gas
gangrene. There is no vaccine.
4. Clostridium difficile
Disease—Pseudomembranous colitis. Characteristics—Anaerobic, gram-positive, spore-forming rods. Habitat and
Transmission—Habitat is the human colon. Transmission is fecal–oral.
Pathogenesis—Antibiotics suppress normal flora of colon, allowing C. difficile to overgrow and produce large amounts of
exotoxins. Exotoxins A and B inhibit GTPases, causing inhibition of signal transduction and depolymerization of actin
filaments. This leads to apoptosis and death of enterocytes. The pseudomembranes seen in the colon are the visual
result of the death of enterocytes.
Laboratory Diagnosis—Exotoxin in the stool is typically detected by using known antibody to the toxin in an ELISA test or
by polymerase chain reaction (PCR) assay. Exotoxin in stool can also be detected by cytopathic effect on cultured cells.
Identified by neutralization of cytopathic effect with known antibody.
Treatment—Metronidazole. Vancomycin, although effective, should not be used because it may select for vancomycin-
resistant enterococci. Prevention—No vaccine or drug is available.