General Characteristics
Basic features of Clostridium species
- Gram-positive bacilli
- Spore-forming organisms
- Obligate anaerobes
- Habitat:
- Soil, fresh water, marine sediments
- Intestinal tract of humans and animals
- Cervical-vaginal flora
- Spores can be airborne.
- Pathogenesis:
- Infection can be exogenous (from outside) or endogenous.
- Cause disease by exotoxins or enterotoxin production
A cartoon showing the general structure of the gram-positive Clostridia bacteria
Image by Lecturio.Pathogenic species
- C. perfringens (20%–40% of all isolates)
- Clostridioides difficile
- C. tetani
- C. botulinum
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| Transmission | Ingestion of:
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Clostridium botulinum
Epidemiology
- Foodborne botulism:
- In the United States, most common in Alaskan Natives (via ingestion of aged fish)
- Overall national rate is 0.0068 per 100,000
- Infant botulism:
- Ingestion of spores:
- From raw honey
- From environmental dust
- Highest incidence in Utah, Pennsylvania, and California
- Ingestion of spores:
- Wound botulism: in injection drug users
Transmission
- Adults ingest preformed toxin from food:
- Associated with improper canning
- Sometimes from fermented beverages (e.g., moonshine)
- Infants ingest spores: toxin then produced in vivo
- Wound botulism:
- Wound contamination with spores
- Germination and toxin production in vivo
Pathogenesis
- Botulism is a potentially life-threatening neuroparalytic disease.
- Botulinum neurotoxin:
- Protease that cleaves soluble N-ethylmaleimide sensitive factor (NSF) attachment protein (SNAP) receptor (SNARE) proteins
- Inhibits release of stimulatory acetylcholine (ACh)
- Causes depletion of ACh in neuromuscular junctions
- Results in flaccid paralysis
Pathophysiological mechanism caused by Clostridium botulinum
Introducing the pathogen with its toxin causes hyperexcitation since part of the toxin blocks the motor end-plate from releasing its neurotransmitters into the synapse
Clinical presentation
Adults:
- Prodromal symptoms:
- Nausea/vomiting
- Abdominal pain
- Diarrhea
- Dry mouth
- Sore throat
- Early symptoms:
- Diplopia
- Ptosis
- Dysphagia
- Descending, flaccid paralysis
- Severity may vary.
Infants (floppy baby syndrome):
- Hypotonia
- Feeding difficulties
- Weak cry
- Drooling
- Irritability
Six-week-old infant with botulism
Marked loss of muscle tone, especially in the region of the head and neck
Identification
- Toxin identification from:
- Serum
- Stool
- Vomitus
- Food
- Enzyme-linked immunosorbent assay (ELISA) test
- Mouse bioassay
- Quantitative polymerase chain reaction (PCR): detects toxin genes in the organism
A photomicrograph of Clostridium botulinum bacteria
Image: “Clostridium botulinum” by the CDC. License: Public domain.
Clostridium (Clostridioides) difficile
Epidemiology
- Most common cause of antibiotic-induced colitis (especially associated with clindamycin)
- Carrier rate:
- In healthy adults: 3%
- In hospitalized/institutionalized adults: 8%–10%
- New exposures more likely to result in symptomatic disease
Transmission
- Fecal-oral spore transmission
- Spores transmitted from person to person (poor handwashing)
Pathogenesis
- Produces 2 potent exotoxins
- Inactivate Ras homologous (Rho) guanosine triphosphate (GTP) enzymes (GTPases):
- Enterotoxin A:
- Targets brush border enzymes
- Alters fluid secretion
- Causes watery diarrhea
- Toxin B (10 times more potent):
- Depolymerizes actin
- Disrupts cytoskeleton of enterocytes
- Causes pseudomembranous colitis
- Enterotoxin A:
- Dipicolinic acid in spore core: highly resistant to heat and chemicals
Clinical presentation
Pseudomembranous colitis:
- Abdominal pain
- Profuse watery diarrhea (may occasionally be bloody)
- Leukocytosis
- Associated with recent antibiotic use
Pathologic specimen showing pseudomembranous colitis
Image: “Pseudomembranous colitis” by the pathologist at work. License: Public domain.Identification
- Toxin antigen detection in stool
- PCR for Clostridioides difficile deoxyribonucleic acid (DNA)
Clostridium perfringens
Epidemiology
- Food poisoning:
- 2nd most common cause of foodborne illness
- Estimated 1 million cases each year in the United States
- Soft-tissue infections:
- 30%–80% of open wounds are contaminated with Clostridium species.
- 80% of traumatic gas gangrene cases
- Spontaneous gas gangrene is usually caused by another species: C. septicum.
Transmission
- Spores in the soil: wound contamination
- Spores in reheated meats: food poisoning
Pathogenesis
Myonecrosis (gas gangrene):
- Alpha toxin:
- Hemolytic toxin; essential for disease manifestations and mortality
- Has phospholipase C and sphingomyelinase activity
- Degrades tissue and cell membranes
- Causes small vessel thrombosis and tissue ischemia
- Ischemia creates anaerobic environment → further propagation of C. perfringens
- Also depresses cardiac output and contributes to systemic shock
- Theta toxin (perfringolysin O):
- Pore-forming cytolysin
- Cytotoxic to vascular and immune cells
- Not essential for mortality
Food poisoning:
- Caused by type A strains
- Spores survive cooking temperatures and propagate in improperly stored foods.
- Enterotoxin:
- Disrupts ion transport in the ileum
- Results in watery diarrhea
Clinical presentation
- Foodborne illness:
- Slow-onset watery diarrhea with abdominal cramping
- Vomiting and fever are uncommon.
- 12–24 hours after food consumption
- Self-limiting, resolves in 1–3 days
- Myonecrosis:
- Severe pain
- Tissue crepitus (from gas formation)
- Edema, blisters, and bullae
- Purplish skin discoloration
- Fever, change in mental status
Gas gangrene of the right leg and pelvis
Image: “Gas gangrene” by Engelbert Schröpfer, Stephan Rauthe, and Thomas Meyer. License: CC BY 2.0.Identification
- Gram stain and culture of the tissues/blister fluid
- Blood cultures
- Stool cultures for foodborne illness
- Distinctive growth characteristics:
- Egg yolk agar: forms a cloudy zone
- Catalase negative
- Oxidase negative
- Double zone of hemolysis on blood agar
- Non-motile
- Encapsulated
Clostridium tetani
Epidemiology
- Causes tetanus: a nervous system disorder
- Very rare in resource-rich countries due to widespread vaccination
- Remains endemic in resource-limited countries
Transmission
- Via spores
- Associated with skin puncture wounds:
- Rusty nails
- Barbed wire
- Construction workers
- Will not grow in healthy tissues
- Predisposing factors:
- Localized ischemia
- Devitalized tissue
- Foreign body
- Co-infection with other bacteria
Pathogenesis
- Average incubation period: 8 days
- Retrograde transport of toxin to the central nervous system (CNS)
- Tetanus toxin or tetanospasmin (A/B toxin):
- Protease that cleaves the SNARE protein
- Blocks exocytosis of inhibitory neurotransmitters (gamma-aminobutyric acid (GABA) and glycine) from Renshaw cells in the spinal cord
- Causes accumulation of ACh
- Results in spastic paralysis
Pathophysiological mechanism caused by Clostridium tetani
Tetanospasmin blocks the binding of neurotransmitters (GABA/glycine) to their receptors on the postsynaptic membrane; thus, inhibitory neurotransmission
Clinical presentation
- Generalized:
- Spastic paralysis
- Risus sardonicus
- Trismus (lockjaw)
- Opisthotonus
- Local:
- Only 1 extremity or part of the body involved
- Often progresses to generalized
- Cephalic:
- Predominant involvement of cranial nerves
- May progress to generalized
- Neonatal:
- Results from contamination of the umbilical cord at delivery
- Rare in developed countries
Risus sardonicus in a patient with generalized tetanus
Image: “PMC4946959_cureus-0008-000000000644-i01” by Zunga PM, Tarfarosh SF, Farooq O, Dar IH, Rashid S, & Yaseen U. License: CC BY 3.0.Identification
- Grows at neutral or alkaline pH
- On different anaerobic media:
- Thioglycolate
- Casein hydrolysate
- Blood agar
Prevention
- Toxoid vaccine
- For clean wounds, give vaccine:
- If < 3 previous doses
- If last dose > 10 years ago
- For contaminated wounds:
- Give vaccine if last dose > 5 years ago.
- Give human tetanus immune globulin if < 3 doses of toxoid vaccine.
References
- Brooke I. (1988). Clostridium species (Clostridium perfringens, C. butyricum, C. clostridioforme, C. innocuum, C. ramosum, C. septicum, C. sordellii, C. tertium). http://antimicrobe.org/b90.asp
- Knapp, S. (2020). Clostridium botulinum. https://biologydictionary.net/clostridium-botulinum/
- Lamont J.T., Kelly C.P., Bakken J.S. (2020). Clostridioides (formerly Clostridium) difficile infection in adults: Clinical manifestations and diagnosis. UpToDate. Retrieved December 25, 2020, from https://www.uptodate.com/contents/clostridioides-formerly-clostridium-difficile-infection-in-adults-clinical-manifestations-and-diagnosis?search=clostridium%20difficile&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2
- LaRocque R., & Harris J.B. (2019). Causes of acute infectious diarrhea and other foodborne illnesses in resource-rich settings. UpToDate. Retrieved December 23, 2020, from https://www.uptodate.com/contents/causes-of-acute-infectious-diarrhea-and-other-foodborne-illnesses-in-resource-rich-settings?search=clostridium%20perfringens&source=search_result&selectedTitle=2~40&usage_type=default&display_rank=2
- Pegram P.S., & Stone S.M. (2020). Botulism. UpToDate. Retrieved December 25, 2020, from https://www.uptodate.com/contents/botulism?search=botulism&source=search_result&selectedTitle=1~68&usage_type=default&display_rank=1
- Sexton D.J., & Thwaites L. (2020). Tetanus. UpToDate. Retrieved December 25, 2020, from https://www.uptodate.com/contents/tetanus?search=tetanus&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H16
- Stevens D.L, & Bryant A. (2020). Clostridial myonecrosis. UpToDate. Retrieved December 23, 2020, from https://www.uptodate.com/contents/clostridial-myonecrosis?search=clostridium%20perfringens&source=search_result&selectedTitle=1~40&usage_type=default&display_rank=1
