Statement: Drugs for Possible Exposure to Anthrax
October 18, 2001
Sidney M. Wolfe, M.D., Larry Sasich, Pharm. D, M.P.H. and Peter Lurie, M.D., M.P.H.
Public Citizen's Health Research Group
With each new day come new reports of exposures, possible exposures and what turn out to be fake exposures to anthrax. Originally coming from Florida, reports are now emanating from other states including New York, Nevada and the District of Columbia. Although it is likely that the majority of scares about anthrax will not turn out to actually involve the potentially lethal bacteria, public concern and fear is quite understandable since, at this writing, there has been one death in Florida in a man exposed to anthrax and several who have become ill.
The main scenario that has fueled public concern is one in which people have been or believe they have been exposed to anthrax and are desperate to prevent their possible exposure from causing them to contract the disease. Thus, they seek to be treated before any symptoms begin. Given that the anthrax disease is not at all communicable from person to person, the route of this exposure would have to be spores ? the dormant form of the bacteria ? either inhaled, which can lead to the pulmonary type of anthrax or touched, leading to the variety of anthrax which affects the skin. Less likely is ingestion that could lead to the more unusual gastrointestinal form of the disease. (See the discussion of anthrax background at the end of this statement.)
Debate has centered on what antibiotic people should take after possible exposure to anthrax spores has occurred. This type of treatment is referred to as post-exposure prophylaxis. Fueling the rush of people to stockpile Cipro (ciprofloxacin), the antibiotic most often mentioned as a way of preventing disease in people who may have been exposed to anthrax spores, are misperceptions resulting from a lack of information. This has included the idea that only ciprofloxacin is effective in prevention of disease in those exposed.
A September 1999 U.S. Army report, titled Medical Management of Biological Casualties Handbook recommended that, for people who have been or may have been exposed to anthrax spores, "prophylaxis with ciprofloxacin (500 mg orally twice a day) or doxycycline (100 mg orally twice a day) is recommended."[Emphasis added]
For obvious ethical reasons, no human experiments were the basis for this recommendation but experiments on monkeys at Ft. Detrick in the early 1990s found that a 30-day post-exposure prophylaxis regimen with doxycycline or ciprofloxacin was approximately 90% effective in preventing anthrax in animals exposed one day before starting the drug to high concentrations of anthrax spores in the air. The current recommendation of 60 days treatment for exposed people was probably based on this animal study because the two drugs were, in fact, 100% effective in preventing anthrax during the 30 days they were still being used and the cases which occurred (one each in the doxycycline and ciprofloxacin groups) were between the discontinuation of the drugs after 30 days and 60 days after exposure to the anthrax spores.
Unlike ciprofloxacin, which is still on patent to Bayer and which costs over $500.00 for a recommended 60 day course of treatment, doxycycline is available in a generic form and costs less than one-tenth as much, approximately $50.00, for 60 days of treatment.
Another issue about which there has not been clarity in the media is that a distinction must be drawn between the treatment of an established anthrax infection and the prevention of anthrax infection after inhaling or otherwise having contact with anthrax spores: post-exposure prophylaxis. The U.S. Food and Drug Administration (FDA) has approved five drugs for the treatment of established anthrax infection: Ciprofloxacin (Cipro), tetracycline (various generics), minocycline (Minocin and various generics), doxycycline (Vibramycin and various generics) and penicillin (various generics). However, only ciprofloxacin, a member of the fluoroquinolone family of antibiotics, has been approved by the FDA for the post-exposure prophylaxis. There is apparently a current effort to expedite the FDA approval, for post-exposure prophylaxis, of doxycycline and penicillin. (penicillin was less effective in the Ft. Detrick study)
In the late 1990s, the government approached Bayer, the manufacturer of ciprofloxacin, and urged it to seek FDA approval for post-exposure prophylaxis. This may have been because Cipro is the only one of the candidate drugs still under patent and whose manufacturer therefore had an incentive to seek such approval. Following an FDA advisory committee meeting on July 28, 2000 at which the Ft. Detrick monkey study was heavily relied upon, the FDA gave its approval for Cipro for this purpose.
The use of appropriate antibiotics for post-exposure prophylaxis in the event of possible exposure to anthrax spores is unequivocally warranted, as the benefits of the drug would clearly outweigh its risks. However, if a substantial number of people take a drug in the absence of exposure to anthrax spores, there will be a finite number of individuals who will needlessly suffer substantial morbidity from the drug. There are additional concerns about creating other bacteria (most likely not anthrax) resistant to the antibiotics.
The FDA-approved professional product labeling, or "package insert," for the ciprofloxacin and doxycycline list several contraindications and a number of potentially serious adverse effects associated with the use of these drugs. At the end of this statement are some examples.
What You Can Do
1. Use doxycycline (100 mg twice a day) or ciprofloxacin (500 mg twice a day) to prevent anthrax only if you have had a reasonably probable exposure to anthrax spores. The best current evidence is that they are equally effective in preventing anthrax in people who have been exposed.
2. If after bacterial tests are done on the powder or other substance(s) to which you may have been exposed, it turns out not to have been anthrax, the antibiotics should be immediately discontinued.
3. If anthrax exposure is confirmed, it is essential that you continue taking the antibiotic for the full 60 days in order to reduce if not eliminate the possibility of developing active disease.
4. In order to protect the national supply of drugs, you should not ask your physician for ciprofloxacin or other antibiotics to prevent anthrax infection in the absence of your possible exposure to anthrax spores. Any antibiotics needed for post-exposure prophylaxis should be made available by public health authorities when and where they are needed.
ADVERSE EFFECTS OF CIPRO AND DOXYCYCLINE
The safety and effectiveness of ciprofloxacin in pediatric patients and adolescents less than 18 years of age, pregnant women, and lactating women have not been established. The drug should not be used routinely in these groups except for post-exposure prophylaxis for anthrax.
The following adverse reactions have been documented with ciprofloxacin:
Fatal reactions in patients receiving ciprofloxacin with the asthma drug theophylline (Slo-Bid, Theo-Dur, Quibron-T-SR).
Pseudomembranous colitis (inflammation of the bowel) ranging in severity from mild to life-threatening.
Achilles and other tendonitis and tendon ruptures requiring surgical repair or resulting in prolonged disability.
Neuropsychiatric adverse reactions such as nervousness, agitation insomnia, anxiety, nightmares or paranoia.
Severe sunburn (phototoxicity).
The following adverse reactions have been documented with doxycycline:
Doxycycline and other tetracycline drugs used during the last half of pregnancy, infancy and childhood through the age of eight years may cause permanent discoloration of the teeth.
Phototoxicity: In some people using this drug, simultaneous exposure to sunlight may cause a skin rash.
Reduced effectiveness of oral contraceptives.
Greater risk of bleeding among patients taking the blood thinner warfarin (Coumadin)
Anthrax is primarily a disease of farm animals, with cattle, sheep and horses being the animals usually infected. Human infections may be contracted by contact with contaminated hair, wool, hides, flesh, blood and excreta of infected animals and from manufactured products such as bone meal. Until recently, human cases have been extremely rare.
Anthrax is an unusual bacterium. Unlike most bacteria, it forms spores, which are extremely hardy ? they can persist in some soils for decades. These spores are a dormant form of the bacterium and are resistant to antibiotics. In the body, anthrax spores are consumed by special white blood cells called macrophages, which carry the spores into the lymphatic system. In the macrophages the spores can be transformed into actual bacteria which can invade the blood system, producing a toxin. Several antibiotics can treat the bacteria, but untreated anthrax can lead to rapid death.
There are three distinct anthrax syndromes seen in humans, all contracted from exposure to anthrax spores: 1) cutaneous (skin) anthrax, contracted through scratches or abrasions of the skin; 2) inhalational (breathed) anthrax; and 3) gastrointestinal anthrax, from eating insufficiently cooked infected meat.
The cutaneous form (until now, 95% of U.S. anthrax infections) occurs most frequently on the hands and forearms of persons working with infected livestock. A local skin infection can lead to bacteria entering the blood stream, which can be fatal. Within a week of exposure, a painless black scab appears, surrounded by swelling and small purplish blisters. Cutaneous anthrax resolves without complications or scarring in 80%-90% of patients who receive antibiotics for treatment.
Inhalational anthrax, known as Woolsorters' disease, is a rare infection contracted by inhalation of anthrax spores. It occurs mainly among workers handling infected hides, wool, and furs. Infection spreads from the lungs to the rest of the body, typically 10 days (but as long as six weeks) after exposure. In people who have already become significantly symptomatic, it is usually fatal, even with aggressive antibiotic treatment. This form represents the major terrorist threat at this time. The gastrointestinal form has never been reported in the U.S.
 U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland
 Friedlander AM, Welkos SL, Pitt ML, et al. Postexposure prophylaxis against experimental inhalation anthrax. Journal of Infectious Disease 1993;167:1239-1243.