Ciprofloxacin: Antibiotic for the Treatment of Anthrax

1. Ciprofloxacin: Antibiotic for the Treatment of Anthrax Anne Malhowski and Erin Murphy CHM 357 10.27.04

2. 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

3. 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

4. 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

5. 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

6. Anthrax Life Cycle http://www.ph.ucla.edu/epi/bioter/anthraxlifecycle.html

7. 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

8. Fatality Statistics of Anthrax • Cutaneous – 20% • Inhalation – 75% • Gastrointestinal - 25%-60% *Statistics according to the Center for Disease Control (CDC)

9. 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/anthrax.jpg

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

11. 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

12. 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.

13. 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

14. 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) MW:385.8

15. Structure of Cipro • Cipro XR • Quinolone

16. Side Effects • Gastrointestinal intolerance • Nausea, vomiting, diarrhea • Photosensitivity • Occasionally CNS toxicity • Dizziness and tremors

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