1. ANAEROBIC, SPORE-FORMING GRAM-POSITIVE BACILLI
Clostridium perfringens Clostridium tetani
Clostridium botulinum Clostridium difficile
Clostridium septicum

2. Clostridium perfringens
Causes two distinct diseases:
Gas gangrene
Food poisoning

3. Clostridium perfringens
Pathogenesis
Present in soil, water and sewage, and as a normal resident of the gastrointestinal tract
Spore formation enables the organism to survive in the environment

4. Clostridium perfringens

5. Clostridium perfringens
Pathogenesis
Alpha toxin: A phospholipase C (lecithinase) lyses erythrocytes, platelets, leukocytes and endothelial cells
increased vascular permeability
massive hemolysis and bleeding
tissue destruction
hepatic toxicity
myocardial dysfunction

6. Clostridium perfringens
phosphatidylcholine

7. Clostridium perfringens
Pathogenesis
Beta toxin necrotic lesions in necrotizing enteritis
Epsilon toxin increases vascular permeability
Iota toxin ADP ribosylating lethal toxin, necrotic activity, increases vascular permeability
Enterotoxin released during spore formation in the small intestine, disrupts ion transport

8. Clostridium perfringens
Zone of complete hemolysis caused by theta toxin
Wider zone of partial hemolysis caused by alpha toxin

9. Clostridium perfringens
Transmission
Exogenous exposure (soil, food, trauma, surgery) is more common than endogenous spread
Vegetative cells are part of the normal flora of the colon and vagina

10. Clostridium perfringens
Clinical syndromes
Myonecrosis (gas gangrene)
Life-threatening disease
Muscle necrosis, shock, renal failure
Death frequently within 2 days of onset
Gas generated by the metabolic activity of the rapidly dividing bacteria

11. Clostridium perfringens
Clinical syndromes
Cellulitis: Necrosis of the skin layer (subcutaneous gas)
Fasciitis: Infection of the fascia, suppuration, gas
Food poisoning: Abdominal cramps and watery diarrhea
Necrotizing enteritis: Bloody diarrhea, shock and peritonitis

12. Clostridium perfringens
Clostridial
cellulitis following
compound fracture
of the tibia

13. Clostridium perfringens
Treatment and control
Rapid treatment is essential
surgical debridement
high-dose penicillin G therapy
Proper wound care and use of prophylactic antibiotics can prevent infections

14. Causes tetanus (lockjaw) Small, motile, spore-forming bacillus
Clostridium tetani
Causes tetanus (lockjaw)
Small, motile, spore-forming bacillus
Frequently stains negative
Terminal spores give the appearance of a drumstick

15. Clostridium tetani
Gram stain with
terminal spores

16. Synthesized as an A-B toxin
Clostridium tetani
Pathogenesis
Tetanospasmin
Synthesized as an A-B toxin
B chain binds to a receptor on neuronal membranes

17. Clostridium tetani

18. “A” chain (zinc endopeptidase)
Clostridium tetani
Pathogenesis
Tetanospasmin
“A” chain (zinc endopeptidase)
Localizes in vesicles in presynaptic nerve terminals of inhibitory synapses
Causes the excitatory synaptic activity to be unregulated
Leads to spastic paralysis

19. Oxygen-labile hemolysin Inhibited by serum cholesterol Spore formation
Clostridium tetani
Pathogenesis
Tetanolysin
Oxygen-labile hemolysin
Inhibited by serum cholesterol
Spore formation

20. In fertile soil and the GI tract of many animals and humans
Clostridium tetani
Transmission
In fertile soil and the GI tract of many animals and humans
> 1 million cases worldwide (mortality rate 20-50%)
Half the deaths occurring in neonates
Associated with minor trauma
skin break with contaminated splinter or nail
Germination of spores favored by necrotic tissue and poor blood supply

21. Generalized tetanus (trismus or lockjaw)
Clostridium tetani
Clinical syndromes
Generalized tetanus (trismus or lockjaw)
risus sardonicus: "smile" due to sustained contraction of the facial muscles
Drooling, sweating, persistent back spasms
Cardiac arrythmias, fluctuations in blood pressure, hyperthermia, dehydration
High mortality rate

22. Clostridium tetani
Risus sardonicus
caused by
sustained spasms
of the masseter
muscles

23. Cephalic tetanus: Cranial nerves. Very poor prognosis
Clostridium tetani
Clinical syndromes
Localized tetanus: Involvement of muscles in area of primary injury. Prognosis favorable
Cephalic tetanus: Cranial nerves. Very poor prognosis
Neonatal tetanus: Via umbilical stump. Very poor prognosis when mothers are not immune

24. Debridement of the primary wound Metronidazole or penicillin G
Clostridium tetani
Treatment and control
Debridement of the primary wound
Metronidazole or penicillin G
Human tetanus immunoglobulin
Vaccination with tetanus toxoid
Three doses of tetanus toxoid and a booster every 10 years

25. Clostridium botulinum
Pathogenesis
Botulinum toxin
Similar to tetanus toxin, but inhibits cholinergic synaptic transmission
Binary toxin
Two components that combine to disrupt vascular permeability
Spore formation

26. Clostridium botulinum

27. Clostridium botulinum
Transmission and clinical syndromes
Foodborne botulism
Home-canned foods
Weakness and dizziness 1-2 days later
Blurred vision, dry mouth due to anticholinergic effect of the toxin
Constipation and abdominal pain

28. Clostridium botulinum
Transmission and clinical syndromes
Progressive disease
Weakening of peripheral muscles (flaccid paralysis)
Respiratory paralysis
Complete recovery months to years (regeneration of paralyzed nerve endings)

29. Clostridium botulinum
Transmission and clinical syndromes
Infant botulism
Ingestion of spores in food (contaminated honey)
Colonization of the GI tract
Initial symptoms: constipation, weak cry, failure to thrive

30. Clostridium botulinum
Transmission and clinical syndromes
Wound botulism
Due to infection of wounds
GI symptoms less severe
Other symptoms identical to foodborne disease

31. Clostridium botulinum
Treatment and control
Ventilatory support
Lavage
Metronidazole or penicillin therapy
Botulinum antitoxin against toxins A, B and E
Preventing spore germination by maintaining foods in acid pH and at 4oC
No honey for children younger than 1 year

32. Clostridium difficile
Antibiotic-associated gastrointestinal diseases
Can cause life-threatening pseudomembranous colitis
In soil, water and sewage

33. Clostridium difficile
Pathogenesis
Antibiotics (clindamycin and ampicillin) can alter the normal enteric flora and enable the overgrowth of relatively resistant C. difficile
Disease develops if the organism develops in the colon and produces toxins

34. Clostridium difficile
Pathogenesis
Enterotoxin (toxin A)
Causes hypersecretion of fluid (watery diarrhea) and hemorrhagic necrosis

35. Clostridium difficile
Pathogenesis
Cytotoxin (toxin B)
ADP-ribosylates the GTP-binding protein Rho
Induces depolymerization of actin
Causes damage to the colonic mucosa, leading to pseudomembrane formation

36. Clostridium difficile
Pathogenesis
Adhesin factor
Mediates binding to human colonic cells
Hyaluronidase
Hydrolytic activity
Spores
Survival for months in a hospital environment

37. Clostridium difficile
Clinical syndromes
Diarrhea, associated with pseudomembranes (yellow-white plaques) on the colonic mucosa
Found in the GI tract of about 3% of the general population and up to 30% of hospitalized patients
The most common nosocomial cause of diarrhea

38. Clostridium difficile
Antibiotic
associated colitis
Plaques of fibrin,
mucus and
inflammatory cells

39. Clostridium difficile
Antibiotic
associated colitis
Plaque
Intact intestinal
epithelium

40. Clostridium difficile
Treatment and control
Discontinuation of the implicated antibiotic
Therapy with metronidazole or vancomycin
Resistant spores can be a major source of nosocomial outbreaks

41. In patients with occult colon cancer, acute leukemia and diabetes
Clostridium septicum
Treatment and control
In patients with occult colon cancer, acute leukemia and diabetes
It can spread into tissues and proliferate, causing death within a few days of initial symptoms