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

Clostridium perfringens Causes two distinct diseases: Gas gangrene Food poisoning

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

Clostridium perfringens

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

Clostridium perfringens phosphatidylcholine

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

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

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

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

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

Clostridium perfringens Clostridial cellulitis following compound fracture of the tibia

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

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

Clostridium tetani Gram stain with terminal spores

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

Clostridium tetani

“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

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

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

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

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

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

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

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

Clostridium botulinum

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

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)

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

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

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

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

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

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

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

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

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

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

Clostridium difficile Antibiotic associated colitis Plaque Intact intestinal epithelium

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

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