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Genus Clostridium. Learning objectives:. Describe the basic microbiological features of the genus Clostridium Describe clinical significance of the genus Clostridium List the most clinically important Clostridium species
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Learning objectives: • Describe the basic microbiological features of the genus Clostridium • Describe clinical significance of the genus Clostridium • List the most clinically important Clostridium species • List the main clinical conditions caused by C. perfringens, C. tetani, C. botulinumand C. difficileand describe their major virulence factors
Learning objectives: • Describe the major differences between the main clinical conditions caused by C. perfringens, C. tetani, C. botulinumand C. difficileand describe the laboratory methods used in the diagnosis of each infection • Describe in general the management of the main infections caused by genus Clostridium
Clostridium • > 200 species and sub-species • Thick, Gram-positive, sporing rod • Strict anaerobes • Soil is natural habitat • GIT • Exotoxins and enzymes
Medically important species • C. perfringens • Anaerobic cellulitis and gas gangrene (clostridialmyonecrosis) • C. tetani • Tetanus • C. botulinum • Botulism • C. difficile • Pseudomembranous colitis
Diagnosis of clostridial infections • Identification of the pathogen • Gas gangrene • Identification of the pathogen + toxins • Tetanus, botulism and colitis
Morphology and culturing • Large, Gram-positive rod • Flagellated (except C. perfringens) • Sporulated • Anaerobic atmosphere at 37°C • C. perfringenscolonies are convex, smooth, and hemolytic • Colonies of motile clostridia have an irregular edge
Management • Penicillin G • Antitoxins are used in therapy of tetanus and botulism • Hyperbaric O2 is used to treat gas gangrene • The most important preventive measure against tetanus is active vaccination with tetanus toxoid
Pathogen spectrum • Clostridium perfringens • C. novyi • C. septicum • C. histolyticum
Toxins and enzymes • Toxins: • Necrotizing, hemolytic, and/or lethal activity • Enzymes: • Collagenases, proteinases, DNases, lecithinases, and hyaluronidase
Pathogenesis and clinical picture • Frequently contaminate open wounds • Types of infections: • Anaerobic cellulitis • Gas gangrene (clostridialmyonecrosis)
Anaerobic cellulitis • Infection restricted to the fascial spaces that does not affect musculature • There is no toxemia
Gas gangrene (clostridialmyonecrosis) • An aggressive infection of the muscles • Gas, myonecrosis and toxemia • Medical emergency
Laboratory diagnosis • Specimens • Direct examination • Anaerobic culture • Identification
Tetanus (lockjaw) • Acute clostridial disease • Clinical manifestations caused by strong neurotoxin (tetanospasmin)
Pathogenesis and clinical picture • Pathogens invade tissues following injuries • Toxin produced • Increased muscle tone and spasms
Diagnosis • Toxin detection in wound material • The pathogen is difficult to culture
Treatment • Anti-toxin • Wound cleaning • Muscle relaxants
Botulism • Rare but serious paralytic illness • The toxin enters the human body in one of three ways: • Ingestion of spores (infant botulism) • Toxin ingested with food (adult botulism) • Infected wounds (wound botulism)
Clostridium botulinumtoxin • Very strong neurotoxin • Heat-labile protein • Flaccid paralysis
Clinical picture of classic botulism • Paralysis especially in the nerves of the head • Frequent symptoms: seeing double, difficulty swallowing and speaking, constipation, and dry mucosa
Mortality and cause of death • Mortality: 25–70%, depending on the amount of toxin ingested • Death usually results from respiratory paralysis
Diagnosis and treatment • Diagnosis: • Toxin detection • Therapy: • Anti-toxin
Clostridium difficile • Fecal flora of 1–4% of healthy adults and in 30–50% of children during the first year of life • Pseudomembranous colitis: • Clindamycin • Aminopenicillins • Cephalosporins • Antibiotic-associated colitis
Pathological mechanism • Based on formation of two toxins: • Toxin A is an enterotoxin • Toxin B is a cytotoxin
Laboratory diagnosis • Isolation of the pathogen • Cytotoxin detection in stool filtrates by cytopathic effect • ELISA for toxins “A” and “B”
Treatment • Not always required • Indicated only in severe cases • Metronidazole is the drug of choice