Clostridium (Ditki Notes)

Clostridium Overview

• Rapid-growing bacteria that thrive in anaerobic conditions like the intestinal tract, sewage, water, and soil
• Pathogenic strains produce histolytic toxins, enterotoxins, and neurotoxins
• Four strains cause infection in humans Clostridium difficile, Clostridium perfringens, Clostridium tetani, and Clostridium botulinum

Clostridium difficile

• Common colonizer of the human colon.
• Transmission occurs via the fecal-oral route
• Historically associated with hospitalized patients
• Antibiotics that suppress non-pathogenic colonic flora are a major cause of infection, allowing C. difficile to flourish

C. difficile Virulence Factors

• Toxin A is an enterotoxin that attracts neutrophils, which release cytokines, and increases intestinal wall permeability by attacking colonic epithelial tight junctions.
• Toxin B is a cytotoxin that acts on enterocyte actin to destroy cytoskeletal integrity.
• Binary toxin (CDT) is produced by some C. difficile strains; it may increase bacterial adherence or suppress eosinophil activity

C. difficile Infection

• Acts on the colon, causing gastrointestinal issues from mild diarrhea to severe colitis.
• Pseudomembranous colitis is the most serious form, characterized by yellowish-white exudate on the colon's mucosal surface made of fibrin and inflammatory cells in mucus.

C. difficile Treatment and Prevention

• Withdrawal of the associated antibiotic is often enough for diarrheal symptoms.
• Metronidazole or vancomycin may be administered in more serious cases, but colitis relapse is common
• Fecal microbiota transfer from a healthy donor can replenish bacteria in the colon for patients with multiple relapses

Clostridium perfringens

• Spores are rarely seen clinically
• Colonies are flat, irregular, and beta-hemolytic
• Subtypes exist based on toxin production.

C. perfringens Virulence factors:

• Alpha toxins cause hemolysis, vascular leakage, liver toxicity, and cardiac dysfunction (present in all subtypes)
• Several other toxins form pores and/or induce necrosis
• Food poisoning enterotoxins alter intestinal membrane permeability, leading to fluid and ion loss; this enterotoxin is a superantigen

C. perfringens Infections

• Soft tissue infections include cellulitis, fasciitis, myositis, and myonecrosis
• Myonecrosis, also known as gas gangrene, destroys muscle tissues, and bacterial metabolic activity produces gas bubbles under the skin, potentially leading to death.
• Food poisoning results from consumption of contaminated meat products with enterotoxins acting on the small intestine, leading to abdominal cramps and watery diarrhea

C. perfringens Treatment and Prevention

• Soft tissue infections are treated with antibiotics and surgical debridement

C. perfringens Food Poisoning

• Treatment for food poisoning includes rehydration
• Antibiotics are not recommended because it is self-limiting
• Prevention is achieved by refrigerating and thoroughly reheating foods to at least 74 degrees Celsius

Clostridium tetani

• Distinctive tennis-racket shape during spore formation
• Spores are extremely oxygen-sensitive and can survive in the soil for long periods
• Infection occurs when wounds encounter contaminated soil, providing ideal necrotic and anaerobic environments

C. tetani Virulence Factors

• Tetanospasmin is a heat-labile neurotoxin that blocks the release of inhibitory neurotransmitters, such as GABA and glycine
• The neurotoxin is endocytosed, then transported along axons to neuronal somas in the spinal cord, causing unregulated neuronal excitatory activity.
• Tetanolysin is another toxin produced by C. tetani and is an oxygen-labile hemolysin thought to promote tissue necrosis

C. tetani Infection - Tetanus

• Spastic paralysis is the characteristic feature, manifesting systemically or locally with symptoms like lockjaw, grimace, and opisthotonos
• Can cause fever and sweating
• Cephalic tetanus involves the cranial nerves.
• Maternal tetanus is associated with pregnancy, involving contamination during abortion and delivery
• Neonatal tetanus occurs when infection spreads from the umbilical stump.

C. tetani Treatment and Prevention

• Vaccination effectively prevents tetanus
• Treatment for infection involves wound debridement and administration of metronidazole and antitoxins to prevent death

Clostridium botulinum

• Foodborne disease that contaminates vegetables and meat
• Toxins are protected from degradation within the gastrointestinal tract

C. botulinum Virulence Factors

• Exotoxins A-G; types A, B, and E are most responsible for human infections.
• Toxins are pre-formed, especially in canned goods, which provide ideal alkaline and anaerobic environments.
• Neurotoxins block acetylcholine release at peripheral motor junctions

C. botulinum Infection - Botulism

• Causes descending flaccid paralysis, blurred vision with dilated pupils, dry mouth, and constipation
• Respiratory failure leads to death.
• Wound infection produces similar symptoms; in the US, this form is associated with injection drug use.

C. botulinum Treatment and Prevention

• Treatment includes metronidazole or penicillin and antitoxins
• Respiratory support may be required and gastric irrigation can aid in toxin removal
• Prevention involves boiling home-canned goods and discarding damaged cans
• Honey can contain C. botulinum organisms, so it should not be given to infants.