Ciprofloxacin: Antibiotic for the Treatment of Anthrax

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Ciprofloxacin Antibiotic for the Treatment of
Anthrax

• Anne Malhowski and Erin Murphy
• CHM 357
• 10.27.04

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Anthrax

• Disease caused by Bacillus anthracis, a
  gram-positive spore-forming bacteria
• anthrax spores are found in the soil
• Spores have no smell, taste, or color and are too
  small to be seen by eye
• need an environment that is rich in amino acids,
  nucleosides and glucose to germinate
• Once the germination begins, the disease
  progresses very rapidly
• The anthrax disease is not contagious

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How is anthrax spread?

• Inhalation - spores can be inhaled in
  contaminated soil.
• cutaneous (skin) - spread by biting insects that
  have fed on infected hosts (95 of anthrax cases)
• gastrointestinal caused by ingesting
  undercooked meat or unchlorinated water that
  harbors anthrax bacteria

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Anthrax in a host

• bacteria attacks the lymph nodes
• three proteins are created by the bacteria
  protective antigen (PA)
• edema factor (EF)
• lethal factor (LF)
• the lethal factor cuts mitogen-activated protein
  kinase, an enzyme that controls cell growth and
  is involved in cellular signal transmission
• disrupting signal transmission results in anthrax
  symptoms

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Symptoms of Anthrax

• Inhalation occurs in two stages that surface in
  approximately 7-10 days
• Stage 1 - begins with fever, cough, headache,
  vomiting, chills, weakness, abdominal pain,
  shortness of breath and chest pain.
  (hours-several days)
• Stage 2 - fever, difficulty breathing, sweating,
  a bluish discoloration of the skin, shock, and
  finally death (2-4days)
• Cutaneous occurs within 12 days of exposure
• localized swelling of the skin, which enlarges
  into an ulcer and discharges a clear fluid. Then,
  a black scab will form that falls off in one to
  two weeks.
• Gastrointestinal occurs within several days
• symptoms include nausea, vomiting blood,
  abdominal pain, bloody diarrhea, and weakness
• Results in death for 25 to 60 percent of cases

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Anthrax Life Cycle
http//www.ph.ucla.edu/epi/bioter/anthraxlifecycle
.html
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Diagnosis and Treatment

• Diagnosis through Gram-staining
• A blood sample is cultured and then gram-stained
  to identify the genus level (Bacillus family)
• Cutaneous - vesicular fluid and bloodInhalation
  - blood, cerebrospinal fluid, or chest
  X-rayGastrointestinal - blood
• Treatment
• Anthrax can be treated with the antibiotics,
  penicillin, doxycylcine, or ciprofloxacin.
• If inhalation anthrax is not caught soon, then
  the bacteria would be destroyed but the toxins
  would remain in the system, killing the host.

Gram-stained anthrax
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Fatality Statistics of Anthrax

• Cutaneous 20
• Inhalation 75
• Gastrointestinal - 25-60
• Statistics according to the Center for Disease
  Control (CDC)

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Anthrax as a Biological Weapon

• LD one millionth of a gram
• LD50 2,500 to 55,000 inhaled anthrax spores
• If 100 kg of anthrax spores were released into
  Washington, DC, 130,000 to 3 million would die.
• \
• http//www.brown.edu/Courses/Bio_160/Projects2000/
  Anthrax/epidemiology/infection_statistics.html
• http//images.usatoday.com/news/gallery/terr1015/a
  nthrax.jpg

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Antibiotic

• Antibiotic
• Destroys bacterial cells without harming human
  cells
• Takes advantage of the differing enzymatic make
  up of the two

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Cipro (Ciprofloxacin)

• Cipro
• Antibiotic effective treatment against Anthrax
  bacteria
• Also used in the treatment of UTIs and
  Pyelonephritis
• Kidney infection caused by food borne illness E.
  Coli
• Treats bacterial infections from bronchitis to
  gonorrhea
• Antimicrobial HIV/AIDS medication

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Drug Classification

• Quinolones antimicrobial agent
• Most have excellent bioavailability
• Adverse effects nausea, headache, dizziness, and
  confusion
• Rapidly inhibit DNA synthesis by promoting
  bacterial DNA cleavage in the enzyme components
  of DNA gyrase and type IV topoisomerase
• Resulting in rapid bacterial death
• Exhibit concentration-dependant bacterial killing
• Well absorbed following oral administration
• Drug must be administered every 12 to 24hrs
  because elimination half-lives range from 1.5 to
  16hrs.

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Mechanism of Action

• Inhibits bacterial nuclear DNA synthesis
• Rapid death of bacteria
• Target sight for Cipro is the enzyme DNA gyrase
  (topoismomerase II)
• Responsible for the supercoiling and uncoiling of
  the DNA
• Supercoiling allows long DNA to fit into a cell
• Uncoiling required for replication,
  transcription, and DNA repair
• Cipro prevents bacterial DNA from creating
  enzymes and reproducing

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Pharmacokinetics/Chemistry

• Absorbed from the gastrointestinal tract after
  oral administration
• The unrestricted bioavailability is 70 with no
  significant loss by first pass metabolism
• Elimination half-life is approximately 4hrs
• Urinary excretion of Cipro complete in 24hrs
• Cipro I.V (C17H18FN3O3) MW 331.4
• Cipro XR (C17H18FN3O3 HCl H2O) MW385.8

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Structure of Cipro

• Cipro XR
• Quinolone

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Side Effects

• Gastrointestinal intolerance
• Nausea, vomiting, diarrhea
• Photosensitivity
• Occasionally CNS toxicity
• Dizziness and tremors

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FDA approval

• Approved on July 28th, 2000
• Approved for post-exposure to inhalation anthrax
• Approved under accelerated approval regulations