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![Treatment
Tetanus immune globulin (tetanus antitoxin) is used to
neutralize the toxin.
• The role of antibiotics is uncertain. If antibiotics are used, either
metronidazole or penicillin G can be given.
• An adequate airway must be maintained and respiratory support
given.
• Benzodiazepines (e.g., diazepam[Valium]) should be given to prevent
spasms](https://image.slidesharecdn.com/sheet-220813200900-60742ed2/75/Colysterdum-13-2048.jpg)
![Pathogenesis
Antibiotics suppress drug-sensitive members of the normal flora, allowing Clo.difficile to multiply
and produce exotoxin is A and B. Both exotoxin A and exotoxin B are glucosyltransferases (i.e.,
enzymes that glucosylate [add glucose to] a G protein called Rho GTPase).
The main effect of exotoxin B in particular is to cause depolymerization of actin,resulting in a loss of
cytoskeletal integrity, apoptosis, and death of the enterocytes.](https://image.slidesharecdn.com/sheet-220813200900-60742ed2/75/Colysterdum-39-2048.jpg)
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Colysterdum
- 1. CLOSTRIDIUM Wala Hassan Mustafa M.Sc.microbiology
- 2. Characters of Clostridium •Greek word “kloster” means spindle, • Obligate Anaerobes • Consists of large Gram positive rod shaped . • Arranged in pairs or short chains with rounded pointed ends. • Most clostridia are motile by peri-trichous flagella • All species form endospores and have a fermentative type of metabolism • Have three important qualities: • Multiply only in the absence of oxygen • Have the ability to survive adverse conditions • Release potent toxins during process of multiplying
- 3. Culture Characteristics • Slowgrowth on solid medium • Some produce fluorescent colonies • Haemolysis on blood agar • Sacchrolytic-ferment(CHO) into buteric acid, acetic and alcohal • proteolytic
- 4. Culture Media • Robertson's medium(contain amino acids) • Nutrient agar • Blood agar • Lactose egg yolk milk agar • Mac agar • Cooked meat broth/medium Robert son's cooked meat) • Thioglycolate
- 5. classification There are fourmedically important species: -Clostridium tetani -Clostridium botulinum, -Clostridium perfringens -Clostridium difficile .
- 6. SHAPES OF CLOSTIDIA • Theshape an position of spores varies in different species and is useful the identification of Clostridia Central in Cl.bifermentans Sub terminal in C.perfringens Oval or terminal in Cl.tertium Spherical and terminal giving drum stick in C.tetani
- 7. Clostridium tetani Disease Clo. tetanicauses tetnaus Transmission: Spores are widespread in soil. The portal of entry is usually a wound site (e.g., where a nail penetrates the foot)
- 8. • Causative agentof tetanus • Found in soil, intestinal tracts, and feces of animals. • Small, motile • Spore-forming (drumstick appearance); • Extremely sensitive to oxygen toxicity.
- 9. Pathogenesis • Contamination ofdevitalized tissue • (wound, burn, injury, surgical suture) • Becomes contaminated with C. tetani spores • Migrates along neural paths from local wound • Tetanolysin • Tetanospasmin • responsible for clinical manifestations of tetanus. • An A-B toxin, released when the bacteria lyse.
- 10. • Subunit Ais a zinc endopeptidase that acts on CNS: • Inhibits release of an inhibitory mediator • GABA or glycine) • which acts on postsynaptic spinal neurons (causing spastic paralysis) • Germination of the spore and production of toxin are aided by conditions that lead to low oxidation-reduction potential • Necrotic tissue • calcium salts • associated pyogenic infections
- 11. Clinical Disease • Incubationperiod: 4-5 days. • Symptoms • convulsive tonic contraction of voluntary muscles • Spasms involve first the area of injury, then the muscles of the jaw (trismus or lockjaw; risus sardonicus). • Other voluntary muscles become involved gradually, resulting in generalized tonic spasms (opisthotonos). • Death usually results from interference with respiration. • The mortality rate of generalized tetanus • ~50%.
- 12. • In moresevere cases, • the autonomic nervous systems are also involved. • Localized tetanus • confined to the musculature of primary site of infection • Cephalic tetanus • site of infection: head • Generalized tetanus • 80% prevalence • Lockjaw • Neonatal tetanus • mortality > 90%, and developmental defects are present in survivors.
- 13. Treatment Tetanus immune globulin(tetanus antitoxin) is used to neutralize the toxin. • The role of antibiotics is uncertain. If antibiotics are used, either metronidazole or penicillin G can be given. • An adequate airway must be maintained and respiratory support given. • Benzodiazepines (e.g., diazepam[Valium]) should be given to prevent spasms
- 14. Prevention Tetanus is preventedby immunization with tetanus toxoid (formaldehyde-treated toxin) in childhood and every 10 years there after. • Tetanus toxoid is usually given to children in combination with diphtheria toxoid and the acellular pertussis vaccine (DTaP). • • When trauma occurs, the wound should be cleaned and debrided, and tetanus toxoid booster should be given. • If the wound is grossly contaminated,tetanus immune globulin, as well as the toxoid booster, should be given and penicillin administered.
- 15. 2. Clostridium botulinum Disease Clo.botulinum causes botulism. Transmission Spores, widespread in soil, contaminate vegetables and meats. When these foods are canned or vacuum- packed without adequate sterilization, spores survive and germinate in the anaerobic environment. The toxin is relatively heat-labile; it is inactivated by boiling for several minutes. Thus, disease can be prevented by sufficient cooking.
- 16. • Gram positive •Obligate anaerobic bacillus • Spores • Ubiquitous • Resistant to heat, light, drying and radiation • Specific conditions for germination • Anaerobic conditions • Warmth (10-50oC) • Mild alkalinity
- 17. Pathogenesis Botulinum toxin isabsorbed from the gut and carried via the blood to peripheral nerve synapses, where it blocksrelease of acetylcholine. • It is a protease that cleaves the proteins involved in acetylcholine release. The toxin is a polypeptide encoded by a lysogenic phage • it is among the most toxic substances known. There are eight immunologic types of toxin; types A, B, and E are the most common in human illness. • Botox is a commercial preparation of exotoxin A used to remove wrinkles on the face. • Minute amounts of the toxin are effective in the treatment of certain spasmodic muscle disorders such as torticollis, “writer’s cramp,” and blepharospasm.
- 18. Clinical Signs • Nausea,vomiting, diarrhea • Double vision • Difficulty speaking or swallowing • Descending weakness or paralysis • Shoulders to arms to thighs to calves • Symmetrical flaccid paralysis • Respiratory muscle paralysis
- 19. Laboratory Diagnosis The organismis usually not cultured. • Botulinum toxin is demonstrable in uneaten food and the patient’s serum by mouse protection tests. • Mice are inoculated with a sample of the clinical specimen and will die unless protected by antitoxin.
- 20. Treatment Trivalent antitoxin (typesA, B, and E) is given, along with respiratory support. • The antitoxin is made in horses, and serum sickness occurs in about 15% of antiserum recipients.
- 21. Prevention • Proper sterilizationof all canned and vacuum-packed foods is essential. • Food must be adequately cooked to inactivate the toxin. • Swollen cans must be discarded (clostridial proteolytic enzymes form gas, which swells cans)
- 22. 3 -C. perfringens •Gram positive • Rod-shaped • Non-motile • Anaerobic • Five types of strains • A - E • Four lethal toxins • Alpha, Beta, Epsilon and Iota • Negler’s reaction
- 23. Diseases: • Clo. perfringenscauses two distinct diseases: gas gangrene food poisoning depending on the route of entry into the body.
- 24. A: Gas Gangrene •Gas gangrene (myonecrosis, necrotizing fasciitis ) Gas gangrene is also caused by other histotoxic clostridia such asClostridium histolyticum, Clostridium septicum, Clostridium novyi , and Clostridium sordellii . (Clo. sordellii also causes toxic shock syndrome in postpartum and postabortion woman.)
- 25. Transmission • Spores arelocated in the soil; vegetative cells are members of the normal flora of the colon and vagina. • Gas gangrene is associated with wounds, automobile and motorcycle accidents, and septic abortions (endometritis).
- 26. Pathogenesis Organisms grow intraumatized tissue (especially muscle)and produce a variety of toxins. Not highly invasive; requires damaged and dead tissue and anaerobic conditions • Conditions stimulate spore germination, vegetative growth and release of exotoxins, and other virulence factors. • Fermentation of muscle carbohydrates results in the formation of gas and further destruction of tissue.
- 29. Clinical Findings • Pain,edema, cellulitis, and gangrene (necrosis) occur in the wound area • Crepitation indicates the presence of gas in tissues. • Hemolysis and jaundice are common,as are blood-tinged exudates. • Shock and death can ensue.Mortality rates are high
- 30. Laboratory Diagnosis • Smearsof tissue and exudate samples show large gram positive rods. • Spores are not usually seen • The organisms are cultured anaerobically and then identified by sugar fermentation reactions and organic acid production. • Clo. perfringens colonies exhibit a double zone of hemolysis on blood agar. • Egg yolk agar is used to demonstrate the presence of the lecithinase.
- 33. NAGLERS REACTION • Clostridiumis grown in a media containing 6% agar, sheep blood and human serum with antitoxin spread on one half of the plate • Colonies grown on the side with antitoxin shows no opacity due to the neutralization of the alpha toxin by the antitoxin • Colonies on the other half without antitoxin show zone of opacity
- 34. • Treatment: Penicillin Gis the antibiotic of choice. Wounds should be debrided. • Prevention: Wounds should be cleansed and debrided. Penicillin may be given for prophylaxis. • There is no vaccine.
- 35. B: Food Poisoning •Food poisoning is the second disease caused by Clo.perfringens . • Transmission Spores are located in soil and contaminate food. • The heat-resistant spores survive cooking and germinate. • The organisms grow to large numbers in reheated foods, especially meat dishes.
- 36. • Pathogenesis Clo. perfringensis a member of the normal flora in the colon but not in the small bowel, where the enterotoxin acts to cause diarrhea. The mode of action of the enterotoxin is the same as that of the enterotoxin of Staphylococcus aureus(i.e., it acts as a superantigen). • Clinical Findings The disease has an 8- to 16-hour incubation period and is characterized by watery diarrhea with cramps and little vomiting. It resolves in 24 hours.
- 37. • Treatment Symptomatic treatmentis given; no antimicrobial drugs are administered. Prevention There are no specific preventive measures. Food should be adequately cooked to kill the organism
- 38. 4. Clostridium difficile Disease Clo.difficile causes antibiotic-associated pseudomembranous colitis .Clo. difficile is the most common nosocomial (hospital-acquired) cause of diarrhea Transmission The organism is carried in the gastrointestinal tract in approximately 3% of the general population and up to 30% of hospitalized patients. Most people are not colonized, which explains why most people who take antibiotics do not get pseudomembranous colitis. It is transmitted by the fecal–oral route. The hands of hospital personnel are important intermediaries.
- 39. Pathogenesis Antibiotics suppress drug-sensitivemembers of the normal flora, allowing Clo.difficile to multiply and produce exotoxin is A and B. Both exotoxin A and exotoxin B are glucosyltransferases (i.e., enzymes that glucosylate [add glucose to] a G protein called Rho GTPase). The main effect of exotoxin B in particular is to cause depolymerization of actin,resulting in a loss of cytoskeletal integrity, apoptosis, and death of the enterocytes.
- 40. • Clindamycin wasthe first antibiotic to be recognized as a cause of pseudomembranous colitis, but many antibiotics are known to cause this disease. • At present, second- and third-generation cephalosporins are the most common causes because they are so frequently used. Ampicillin and fluoroquinolones are also commonly implicated. In addition to antibiotics, cancer chemotherapy also predisposes to pseudo-membranous colitis • .Clo. difficile rarely invades the intestinal mucosa.
- 41. Clinical Findings • Clo. difficilecauses diarrhea associated with pseudomembranes (yellow-white plaques) on the colonic mucosa • The diarrhea is usually not bloody, and neutrophils are found in the stool in about half of the cases. Fever and abdominal cramping often occur. • The pseudomembranes are visualized by sigmoidoscopy. Toxic megacolon can occur, and surgical resection of the colon may be necessary. • Pseudomembranous colitis can be distinguished from the transient diarrhea that occurs as a side effect of many oral antibiotics by testing the presence of the toxin in the stool.
- 42. Symptoms • Diarrhea • Fever •Abdominal pain • Toxic mega-colon • Increased abdominal pain • Abdominal tenderness • Fever • Tachycardia • Dehydration
- 43. Laboratory Diagnosis The presenceof exotoxins in the filtrate of a patient’s stool specimen is the basis of the laboratory diagnosis. It is insufficient to culture the stool for the presence Note that isolation of Clo. difficile from the stool, followed by evidence that the isolate is a toxin producing one, can be used. However, this process takes time and may not be able to be completed in a clinically relevant time frame. There are two types of tests usually used to detect the exotoxins.1: is an enzyme-linked immunosorbent assay (ELISA) using known antibody to the exotoxins. ELISA tests are rapid but are less sensitive than the cytotoxicity test. 2:In the cytotoxicity test, human cells in culture are exposed to the exotoxin in the stool filtrate and the death of the cells is observed. This test is more sensitive and specific but requires 24 to 48 hours’ incubation time. To distinguish
- 44. Treatment The causative antibioticshould be with drawn. Oral metronidazole or vancomycin should be given and fluids replaced. Also in life-threatening cases, surgical removal of the colon may be required. In many patients, treatment does not eradicate the carrier state, and repeated episodes of colitis can occur
- 45. Prevention There are nopreventive vaccines or drugs. Because antibiotics are an important predisposing factor for PMC, they should be prescribed only when necessary. The use of probiotics to prevent PMC is not recommended
- 46. Important Features ofPathogenesis by Clostridium Species Prevention Action of Toxin Transmission/ Predisposing Factor Disease Organism Toxoid vaccine Blocks release of inhibitory transmitters (e.g., glycine) Spores in soil enter wound Tetanus Clo. tetani Proper canning; cook food Blocks release of acetylcholine Exotoxin in food is ingested Botulism Clo. botulinum Debride wounds Cook food Lecithinase Superantigen Spores in soil enter wound Exotoxin in food is ingested 1. Gas gangrene 2. Food poisoning Clo. perfringens Appropriate use of antibiotics Cytotoxin damages colon mucosa Antibiotics suppress normal flora Pseudomembranous colitis Clo. difficile