Bacteria

Anthrax

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Anthrax, Bacillus anthracis

  • Etiology
  1. Bacillus anthracis
  • Pathophysiology
  1. Pulmonary Macrophages transfer spores from the lung to the mediastinal lymph nodes
  2. Necrotizing Lymphadenitis results, followed by Septic Shock
  • Transmission
  1. No transmission person to person
    1. Contrast with other Bioterrorism agents such as Plague, which do involve person-to-person spread
  2. Contact with hides of infected animals
    1. Cattle
    2. Sheep
    3. Camels
    4. Antelopes
  3. Ingestion of undercooked and contaminated meat
    1. Anthrax invades intestinal mucosa resulting in necrotic ulcers
    2. Maddah (2013) Caspian J Intern Med 4(2): 672-6 [PubMed]
  4. Inhalation of spores
    1. Infective aerosol dose: 8,000-50,000 spores
    2. Spores may remain viable in soil for >40 years
  • Course
  1. Incubation: 4-6 days (range as broad as 1 to 42 days)
  2. Duration of illness: 3-5 days
  • Findings
  • Cutaneous ("Malignant Pustule")
  1. Inoculation at site of broken skin
  2. Painless pruritic Pustules develop at inoculation site
  3. Begins as erythematous Papule on exposed skin
  4. Vesiculates and then ulcerates within 1-2 days
    1. Surrounded by a ring of non-tender Brawny Edema
  5. Black eschar may form
  • Findings
  • Inhalation Anthrax
  1. Malaise
  2. Regional Lymphadenopathy
  3. Two phases
    1. Initial Phase (flu-like illness) for 1-2 days
      1. Fever
      2. Headache
      3. Viral upper respiratory symptoms
      4. Cough
      5. No Pharyngitis or Rhinorrhea (contrast with typical URI)
    2. Middle Phase
      1. Transient improvement for 1-2 days
    3. Later Phase: Rapid Deterioration
      1. High fever
      2. Drenching sweats
      3. Nausea and Vomiting
      4. Dyspnea and Hemoptysis during dissemination
      5. Cyanosis
      6. Shock
      7. Hemorrhagic mediastinitis
      8. Thoracic Lymphadenitis
      9. Hemorrhagic Meningitis
  • Findings
  • Intestinal Anthrax
  • Differential Diagnosis
  1. Cutaneous Anthrax
    1. Spider Bite
    2. Ecthyma gangrenosum
    3. Ulceroglandular Tularemia
    4. Plague
    5. Staphylococcus or StreptococcusCellulitis
  2. Inhalational Anthrax
    1. Community Acquired Pneumonia (late phase Anthrax)
    2. Mycoplasma pneumonia (early phase Anthrax)
    3. Influenza (early phase Anthrax)
    4. Legionnaires' Disease
    5. Psittacosis
    6. Tularemia
    7. Q Fever
    8. Viral Pneumonia
    9. Histoplasmosis (fibrous mediastinitis)
    10. Coccidioidomycosis
  • Labs
  1. Rapid ELISA test now available
  2. Cultures
    1. Blood Culture (high sensitivity)
    2. Cultures of Vomitus or feces (Intestinal Anthrax)
    3. CSF Culture (Inhalational Anthrax)
    4. Nasal Swab (Epidemiologic tool to identify outbreak)
    5. Sputum Culture (Inhalational Anthrax)
    6. Vesicular fluid (Cutaneous Anthrax)
  3. Gram Stain of blood or vesicular fluid from lesion
    1. Large, Gram Positive bacilli
  4. Complete Blood Count
    1. Neutrophilic Leukocytosis in severe cases
  1. Widened Mediastinum (hemorrhagic mediastinitis)
  • Management
  • Suspected Anthrax Contact
  1. Suspicious item management
    1. See Biological and Chemical Weapon Exposure in Mail
  2. Decontamination
    1. Careful Hand Washing with soap and water
    2. No special Decontamination procedures
  3. See Post-exposure Prophylaxis below
    1. Probability of exposure should be assessed
    2. See resources below to address probability
    3. Lab test all patients treated with prophylaxis
  4. Hospitalized Patients with possible Anthrax findings
    1. Public Health to start epidemiologic evaluation
    2. Confirm diagnosis with lab testing (see above)
  • Management
  • Antibiotics for inhalational Anthrax
  1. General
    1. Combine antibiotic regimen with either Monoclonal Antibody (e.g. Rxibacumab) or Anthrax IgG
  2. Initial IV management
    1. Start with IV preparations and then transition to oral when stable
    2. Meningitis (confirmed or suspected)
      1. Ciprofloxacin (or Levofloxacin or Moxifloxacin) AND
      2. Meropenem (or Imipenem or doripenem, or if Penicillin sensitive, Penicillin G or Ampicillin) AND
      3. Linezolid (or Clindamycin or Rifampin or Chloramphenicol)
    3. Without Meningitis
      1. Ciprofloxacin AND
      2. Clindamycin (or Linezolid)
  3. Oral antibiotics (after initial IV) to complete a total of 60 days of antibiotics
    1. Ciprofloxacin or Doxycycline
  4. Antibiotic Dosing
    1. Ciprofloxacin
      1. IV: 7.6 mg/kg up to 400 mg every 8 hours
      2. PO: 15 mg/kg up to 500 mg orally twice daily
    2. Clindamycin
      1. IV: 7.6 mg/kg up to 900 mg every 8 hours
    3. Meropenem
      1. IV: 40 mg/kg up to 2 g every 8 hours
    4. Linezolid
      1. IV: 15 mg/kg up to 600 mg every 12 hours (or 30 mg/kg/day divided q8h if <12 years old)
    5. Doxycycline
      1. PO: 4.4 mg/kg up to 200 mg orally once, then 2.2 mg/kg up to 100 mg twice daily
  5. Monoclonal Antibody or IgG Dosing (used with antibiotic regimen)
    1. Raxibacumab (coadminister with Diphenhydramine)
      1. Weight >50 kg: Give 40 mg/kg IV over 2 hours
      2. Weight >15-50 kg: Give 60 mg/kg IV over 2 hours
      3. Weight <15 kg: Give 80 mg/kg IV over 2 hours
    2. Anthrax IgG
      1. Dosing in number of vials (2-7 each with 60 units) based on weight (10-60 kg)
  1. Regimen
    1. Anthrax Vaccine (BioThrax) at 0, 2 and 4 weeks post-exposure AND
    2. Antibiotic course for 60 days
      1. Start with Ciprofloxacin or Levofloxacin (or Doxycycline)
      2. In pregnancy and children, if Anthrax tested as susceptible, may switch to Amoxicillin after 14 days
  2. Antibiotic Dosing
    1. Ciprofloxacin
      1. Adults: 500 mg orally twice daily
      2. Children: 10-15 mg/kg up to 500 mg orally twice daily
    2. Doxycycline
      1. Adults: 100 mg orally twice daily
      2. Children over age 8 years: 2.5 mg/kg up to 100 mg orally every 12 hours
    3. Amoxicillin (only if susceptible)
      1. Adults: 500 mg orally three times daily
      2. Children: 40 mg/kg up to 500 mg orally three times daily
  • Prognosis
  1. Inhalation Anthrax (inhaled spores)
    1. Untreated: 95% mortality
    2. Treated: 80% mortality
  2. Cutaneous Anthrax (skin contact)
    1. Untreated: 20% mortality
    2. Treated: Rare mortality
  3. Intestinal Anthrax (ingested contaminated meat)
    1. Mortality 25 to 60%
  • Prevention
  1. Anthrax Vaccine 93% effective
    1. Initial: 0, 2, and 4 weeks
    2. Next: 6, 12, 18 months and then annually
  2. Postexposure Prophylaxis as above
    1. Empiric prophylaxis for any suspected exposure
    2. Best prognosis with antibiotics prior to symptoms
  • Resources
  1. Department of Defense Anthrax Vaccine Program
    1. http://www.anthrax.osd.mil
    2. Phone: 877-GETVACC
  2. CDC Bacterial and Mycotic Disease Information
    1. http://www.cdc.gov/ncidod/dbmd/diseaseinfo/
  3. CDC Bioterrorism Preparedness and Response
    1. http://www.bt.cdc.gov
  • Contributing Authors and Editors
  1. Gary Malet, MD
  2. Scott Moses, MD
  • References
  1. (1998) Medical Management Biological Casualties, Army
  2. Gilbert (2016) Sanford Guide Antimicrobial
  3. Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
  4. Inglesby (1999) JAMA 281(18):1735-45 [PubMed]
  5. Sweeney (2011) Am J Respir Crit Care Med 184(12):1333-41 [PubMed]