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Cl tetani + cl difficile
 

Cl tetani + cl difficile

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  • 1995-1997 is the most recent summary of tetanus cases reported in the U.S.
  • This slide illstrates the pathogeneis of CDAD AB=antibiotic, AN=antineoplastic Each gram of human stool contains 10**12 (a trillion) bacteria belonging to over 30 genuses and 400 to 500 species; this biomass protects against C.difficile colonization Antibiotics or some Antineoplastic agents (esp. those with antibiotic activity) kill off this protective biomass enabling C. difficile acquired by the fecal-oral route to colonize the colon As C. difficile proliferates it begins to release two exotoxins, named A and B, that mediate the diarrhea and bowel inflammation seen in this disease These toxins are some of the most lethal bacterial toxins studied and are active against over 20 kinds of mammalian cell lines and tissues Once toxin A and B gain access to the cytoplasm of bowel mucosa cells, they disrupt the skeleton of these cells causing them to round up, retract, and lose their intercellular connections. The cells also die. Toxin A also causes intestinal fluid secretion

Cl tetani + cl difficile Cl tetani + cl difficile Presentation Transcript

  • Clostridium tetani Clostridium difficile Dr Kamran Afzal Asst Prof Microbiology
  • Clostridium tetani Tetanus
  • Clostridium tetani
    • Anaerobic, heat sensitive GPR
    • A terminal spore gives it a drumstick appearance
    • Spores found in soil, animal feces
      • May persist for months to years
    • Tetanolysin - function is not known with certainty
    • Tetanospasmin
      • Neurotoxin that causes the clinical manifestations of tetanus
      • Estimated human lethal dose = 2.5 ng/kg
      • The toxin travels via intra axonal transport at a rate of 75 -250 mm/day -> 2 -14 days to reach the CNS
  • Clostridium tetani
  • History of Tetanus
    • First described by Hippocrates
    • Etiology discovered in 1884 by Carle and Rattone
    • Passive immunization used for treatment and prophylaxis during World War I
    • Tetanus toxoid first widely used during World War II
  • Tetanus
    • Tetanus is an acute, often fatal disease caused by an exotoxin produced by the bacterium Clostridium tetani
    • It is characterized by generalized rigidity and convulsive spasms of skeletal muscles
    • The muscle stiffness usually involves the jaw (lockjaw) and neck and then becomes generalized
    • Mode of Transmission
      • Contaminated wounds
      • Tissue injury (surgery, burns, deep puncture wounds, crush wounds, otitis media, dental infection, animal bites, abortion, and pregnancy)
  • Epidemiology
    • Reservoir Soil and intestine of animals and humans
    • Temporal pattern Peak in summer or wet season
    • Communicability Not contagious
    • Mortality rate Increases >60 years age
  • Injuries and Conditions Data available for 129 of 130 reported cases. Source: MMWR 2003;52(SS-3):1-12
  • Pathogenesis
    • Cl tetani usually enters the body through a wound
    • Anaerobic conditions -> germination of spores and production of toxin -> disseminated via blood and lymphatics
    • Toxin reaches the CNS by passing along the motor nerves to the anterior horn cells of the spinal cord
      • Interferes with neurotransmitter release -> block inhibitory impulses
      • Leads to unopposed muscle contraction and spasm
        • The shortest peripheral nerves are the first to deliver the toxin to the CNS, which leads to the early symptoms of facial distortion and back and neck stiffness
    ->
  • How Tetanospasmin reaches the CNS?
  • Mechanism of Action of Tetanus Toxin
  • Types of Tetanus - Etiology
    • Traumatic Tetanus
    • Puerperal Tetanus
    • Otogenic Tetanus
    • Idiopathic Tetanus
    • Tetanus Neonatorum
  • Clinical Features
    • Incubation period: 8 days (Range: 3-21 days)
    • Three clinical forms
      • Generalized (most common)
      • Local (not common)
      • Cephalic (rare)
    • Generalized tetanus (about 80%)
      • Descending symptoms of trismus (lockjaw), difficulty swallowing, muscle rigidity, spasms
      • Spasms continue for 3-4 weeks
      • Neonatal tetanus is a form of generalized tetanus
        • Infant born without protective passive immunity
  • Sequence of events
    • Lock Jaw
    • Stiff Neck
    • Difficulty Swallowing
    • Muscle Rigidity
    • Spasms
  • Clinical Confirmation
    • Following features
    • Risus sardonicus or fixed sneer
    • Lock jaw
    • Opisthotonos
      • Extension of lower extremities, flexion of upper extremities and arching of the back
      • The examiners hand can be passed under the back of the patient when he lies on the bed in supine position
    • Neck rigidity
  • Clinical Diagnostic Tests
    • Spatula Test
      • Posterior pharyngeal wall is touched with a spatula and a reflex spasm of the masseters indicates a +ve test
    • The altered whistle
      • This explained as an early effect of ↑ tone in facial muscles which causes the classic R. sardonicus
  • Laboratory Diagnosis
    • There are no laboratory findings characteristic of tetanus
      • Cl tetani is recovered from the wound in only 30% of cases
    • Demonstration of toxin production in mice
      • Laboratory identification of the organism depends most importantly on this
    • The diagnosis is entirely clinical
      • Does not depend upon bacteriologic confirmation
  • Complications
    • Fractures
    • Hypertension
    • Nosocomial infections
    • Pulmonary embolism
    • Aspiration pneumonia
    • Laryngospasm
    • Malnutrition
    • Gleno-humeral and TMJ dislocations
    • Adverse effects of autonomic instability, (cardiac dysrhythmias and hypertension)
    • Coma, neuropathies, and psychological after effects
    • Death
  • Treatment
    • Medical treatment
    • Wound management
  • a. Medical Treatment
    • Aim is to:
    • provide supportive care
    • eliminate the source of toxin
    • neutralize the circulating toxin to prevent its continued spread
      • Tetanus immune globulin (TIG) (passive immunization)
      • TIG can only help remove unbound tetanus toxin, but it cannot affect toxin bound to nerve endings
      • A single IM dose of 3000-5000 units
    • Drugs
    • Antibiotics
      • Penicillin G
      • Metronidazole
      • Doxycycline
    • Other drugs
      • Diazepam
      • Phenobarbital Anticonvulsants
      • Skeletal muscle relaxants
  • b. Wound Management
    • All wounds should be cleaned with H 2 O 2 and antiseptic
    • Necrotic tissue and foreign material should be removed
  • Assess Wound
  • Prevention
    • Passive immunization
    • Active immunization, or both
    • Tetanus Toxoid (Td)
    • Formalin-inactivated tetanus toxin
    • Pri Schedule Three or four doses (0,1,6 mo) + booster Booster every 10 years
    • Efficacy Approximately 100%
    • Duration Approximately 10 years
    • Should be administered with diphtheria toxoid as DTaP, DT, Td, or Tdap
  • Td and TIG
    • Vaccination History
    • Unknown or less than 3 doses
    • 3 or more doses
    Td* TIG Yes No No + No Td* TIG Yes Yes No** No Clean, minor wounds All other wounds
    • Passive Immunization
    • ATS (equine)
    • ATS (human)
  • Clostridium difficile PMC CDAD AAD
  • Clinical Conditions
    • Pseudomembranous colitis (PMC)
      • Endoscopic demonstration of exudative lesions
    • Clostridium difficile -associated diarrhea (CDAD)
      • Diarrhea + positive stool test
    • Antibiotic-associated diarrhea (AAD)
      • Cl difficile is only one cause
  • Cl difficile
    • Obligate anaerobe
    • Motile, GPR
    • Oval, sub-terminal spores
    • >90% - pseudomembranous colitis
  • Cl difficile Toxins
    • Toxigenic strains produce 2 major toxins
      • Toxin A (enterotoxin)
        • mediates alteration in fluid secretion, enhances inflammation, induces post-capillary venules to leak albumin
      • Toxin B (cytotoxin)
        • more active in causing damage to and exfoliation of superficial epithelial cells
        • activate release of cytotoxins from monocytes
    • Both cause electrophysiologic alterations of colonic tissue
  • Virulence Factors
  • Disruption of protective colonic flora Colonization with toxigenic Cl difficile by fecal-oral transmission Toxin A and B production A/B: Cytoskeletal damage, loss of tight junctions A: Mucosal injury, inflammation, fluid secretion Colitis and Diarrhea Colonization with toxigenic Cl difficile by fecal-oral transmission Colonization with toxigenic Cl difficile by fecal-oral transmission
  • Formation of Pseudomembrane
  • Formation of Pseudomembrane Plaque
  • Antibiotic Risk
    • High Risk Antibiotics
    • Cefotaxime
    • Ceftriaxone
    • Cefalexin
    • Cefuroxime
    • Ceftazidime
    • Ciprofloxacin
    • Moxifloxacin
    • Clindamycin (low dose)
    • Medium Risk Antibiotics
    • Meropenem
    • Ertapenem
    • Clindamycin (high dose)
    • Co-amoxiclav
    • Tazocin
    • Erythromycin
    • Clarithromycin
    • Low Risk Antibiotics
    • Benzyl penicillin Gentamicin
    • Amoxicillin Metronidazole
    • Flucloxacillin Vancomycin
    • Tetracyclines Teicoplanin
    • Trimethoprim Synercid
    • Nitrofurantoin Linezolid
    • Fusidic acid Tigecycline
    • Rifampicin Daptomycin
  • Clinical Manifestations
    • Asymptomatic carriage (neonates)
    • Diarrhoea (CDAD)
        • 1 day after starting to 10 weeks after stopping antibiotics
        • Toxins detectable in stool (95%)
        • brief, self limiting
        • abdominal cramps
        • cholera-like - 20X/day, watery stool
        • blood or mucus may be present in stools
        • fever and leukocytosis
    • Acute toxic megacolon
      • acute dilatation of colon
      • systemic toxicity
      • high mortality (64%)
    • Pseudomembrane formation (PMC)
      • mucosa shows raised plaques with skip areas
    • Colonic perforation
  • Lab Diagnosis
    • Microscopy
      • Large numbers of RBCs and WBCs in stool
    • EIA (can detect A and B)
      • Cytotoxin
      • Antigen
    • Anaerobic Culture (with strain identification)
      • CCFA: cycloserine, cefoxitin, fructose agar
      • Difficult, not routine for most labs
    • PCR toxin gene detection
  • Other Diagnostic Criteria
    • Endoscopy
      • Pseudomembranes
    • Radiology
      • Toxic megacolon
      • Thumb printing effect
    • Surgical or autopsy specimen
      • Positive Histopathology
  • Endoscopic Appearance
  • Toxic Megacolon
  • “ Thumb printing” effect
  • Treatment
    • Discontinue offending antibiotic(s)
    • Avoid anti-peristaltic agents
    • Supportive care (hydrate, electrolytes)
    • Antibiotic therapy
      • Oral Metronidazole: 250 mg qid or 500 mg TID for 10 d
        • Low cost, effective
      • Oral Vancomycin: 125-250 mg QID for 10 days
        • High cost
  • Prevention
    • Use Contact Precautions
      • Place these patients in private rooms
      • Use soap and water for hand hygiene when caring for patients with C . difficile -associated disease
      • Use gloves when entering patients rooms and during patient care
      • Use gowns if soiling of clothes is likely
    • Use antibiotics judiciously
    • No rectal temps
    • Room cleaning with 1:10 bleach solution