Tetanus

• Tetanus


  An acute disease manifested by skeletal muscle spasm and autonomic nervous system disturbance
• Clostridium tetani


  An anaerobic, gram-positive, slender motile bacillus that produces a powerful neurotoxin called tetanospasmin
• Tetanospasmin mechanism of action


  1. Binds to peripheral nerve terminals

  2. Carried intra-axonally within membrane-bound vesicles to spinal neurons and inhibitory interneurons

  3. Blocks release of neurotransmitters
• Tetanospasmin binding


  Irreversible, recovery requires generation of new axon terminals
• Tetanus is often associated with rusty nail but may follow deep puncture wounds, burn, ear or dental infection or abortion
• Clostridium tetani can live as spores for years in soil or animal feces

  
• Tetanospasmin


  A neurotoxin that inhibits the release of γ-aminobutyric acid (GABA) and results in clinical signs of tetanus
• Forms of tetanus


  • Generalized
  • Localized
  • Cephalic
  • Neonatal

  
• Generalized tetanus


  • Most common form, accounts for 85-90% of reported cases
  • Incubation period of 7-21 days
  • Onset period of less than 48 hours associated with more severe symptoms

  
• Trismus


  Spasm of the masseter muscles causing difficulty in opening the mouth and masticating
• Symptoms of generalized tetanus

  • Tonic rigidity spreading to face, neck and trunk muscles
  • Risus sardonicus (contraction of frontalis and muscles at angles of mouth)
  • Opisthotonus (arched back)
  • Board-like abdominal wall

  
• Severe generalized tetanus


  • Violent spasms lasting seconds to minutes
  • Increase in frequency and severity over 1 week
  • Death from exhaustion, asphyxia or aspiration pneumonia
• Autonomic disturbance in severe tetanus


  • Labile blood pressure with rapid fluctuations
  • Tachycardia or bradycardia
  • Hyperpyrexia and sweating
• Localized tetanus


  • Weakness or intense, painful spasms of the involved extremity
  • May progress to generalized tetanus

  
• Cephalic tetanus


  • Isolated or combined dysfunction of cranial motor nerves, most frequently the seventh cranial nerve
  • Incubation period of 1-2 days
  • Poor prognosis for survival
• Neonatal tetanus


  • Generalized tetanus in newborns, accounts for up to half of neonatal deaths in underdeveloped countries
  • Usual cause is use of animal dung or "dusting powder" on umbilical cord
  • Incubation period of 3-10 days
  • Mortality rate exceeds 70%

  
• Diagnosis of tetanus is usually based on clinical observations, causative agent C. tetani is infrequently recovered from wound cultures

  
• Conditions that mimic generalized tetanus include strychnine poisoning and dystonic reactions to antidopaminergic drugs

  
• Treatment of tetanus


  1. Respiratory support

  2. Benzodiazepines for spasm control

  3. Autonomic nervous system support

  4. Passive and active immunization

  5. Surgical debridement

  6. Antibiotics against C. tetani

  
• Tetanus immune globulin (TIG)


  Preparation of choice for passive immunization, less likely to cause anaphylactic reactions

  
• Tetanus toxoid


  Used for active immunization, helps produce antibodies against C. tetani

  
• Management of autonomic nervous system dysfunction


  1. Labetalol for blood pressure control

  2. Morphine, magnesium sulfate, or epidural blockade for hypertension

  3. Norepinephrine for hypotension

  4. Pacemaker for bradycardia
• Tetanus is a disease of medical neglect, immunization is virtually 100% effective

  
• Prevention of tetanus after injury


  1. Appropriate wound management

  2. Assurance of adequate immunity

  3. Antibiotic prophylaxis

  
• Overall mortality rate for generalized tetanus is 20-25%, most frequent cause of death is pneumonia

  
• Clostridium difficile infection (CDI)


  Gastrointestinal infection characterized by diarrhea and positive test for C. difficile toxin

  
• Risk factors for CDI


  • Antimicrobial use
  • Advanced age
  • Stay in acute or chronic care facility

  
• Hospitals are high-risk environments for CDI due to asymptomatic carriage and poor hand hygiene
• Antimicrobials associated with highest CDI risk


  • Clindamycin, cephalosporins, fluoroquinolones

  
• CDI is rare in children and young adults despite frequent antimicrobial exposure, but children under 1 year are commonly colonized with C. difficile without symptoms
• Antimicrobial administration


  Disrupts normal protective bowel flora, allowing C. difficile spores to germinate and produce toxins

  
• Toxin A and Toxin B

  Toxin A is an enterotoxin, Toxin B is a cytotoxin
• Spectrum of CDI

  • Asymptomatic carriage
  • Mild "nuisance مزعجةdiarrhea"
  • Severe pseudomembranous colitis with fluid/protein losses, fever, cramps, hypoalbuminemia, leukocytosis, hypotension
  • Complications like toxic megacolon, renal failure, lactic acidosis

  
• Diagnosis of CDI


  1. Detect toxins A and B in stool by enzyme immunoassay

  2. Detect toxin-producing strain of C. difficile in stool 3-PCR

  
• Treatment of CDI


  1. Mild CDI: Metronidazole 500 mg orally 3 times daily for 10-14 days M=M

  2. Severe CDI: Vancomycin 125 mg orally 4 times daily for 10 days

  3. Recurrent CDI: Repeated courses of antibiotics, often with tapering and pulse-dose regimens
• Majority (70%) of CDI patients respond to simple withdrawal of implicated antibiotic and a single course of metronidazole or vancomycin
• Attributable mortality rate for CDI is as high as 7%, majority of lethal cases occur in patients over 65 years