Introduction Suppose you develop a bladder or sinus infection and go to your doctor. Let''s say your doctor does the right thing by informing you fully, saying, "Cipro is the best drug for this problem. However, drugs like Cipro are believed to cause more than 55,000 serious, sometimes disabling, sometimes permanent reactions each year. Do you still want to take it?" Would you say, "Yes, please?" Not likely. Yet, Cipro and other antibiotics just like it are prescribed to patients every day, often for minor afflictions that do not warrant the use of such a powerful drug. Introduced in 1987 as the first oral medication of its kind, Cipro, or by its generic name, ciprofloxacin, belongs to a class of drugs known as fluoroquinolone antibiotics. Fluoroquinolones (FQs) are particularly potent drugs that are used to treat many different types of infections. However, they are also known for causing debilitating, long-lasting side effects.

Despite this alarming fact, fluoroquinolones are one of the most commonly prescribed drugs in America. A NATION IN PANIC On September 18th, 2001, just a week after the terrorist attacks on the World Trade Center, five envelopes containing a strange granular substance were mailed to each major news source in America. One month later, an employee at American Media, Inc. died of inhalation anthrax, a rare but serious bacterial infection in the lungs. His death was closely followed by the discovery of more letters contaminated with what was determined to be a potent strain of anthrax spores. The nation, still reeling from 9/11, went into hysteria. Over the course of the months that followed, a total of five people died and many more were afflicted with anthrax in a mysterious case of bioterrorism committed against American civilians. When the United States Centers for Disease Control (CDC) recommended Cipro as a preventative measure for anthrax exposure, I was concerned.

I had spent two years collecting data, writing and rewriting, and then shepherding my article, "Peripheral Neuropathy Associated with Fluoroquinolone Antibiotics," toward publication. It wasn''t easy. Several of the peer reviewers didn''t like what I was saying in the article and tried to block its approval. Fortunately, the publisher stood firm and set the date for publication to December 2001. After the anthrax scare in October, the publisher and I felt the information was urgently needed when Cipro became a household name and people began taking or hoarding it without medical basis. Cipro''s downsides weren''t widely known then, even among doctors. Yet, many of the forty-five subjects of my study were injured or disabled years after taking Cipro, suffering from neurological, musculoskeletal, psychiatric, and cardiac reactions to the drug. THE PRESS RELEASE The press release accompanying my article, "Peripheral Neuropathy Associated with Fluoroquinolone Antibiotics," appeared on October 22, 2001: Adverse effects associated with the use of ciprofloxacin (Cipro) and other fluoroquinolone antibiotics are not always benign.

Not infrequently, they can be severe and permanently disabling, and they may occur following just one or a few doses, according to a study posted on The Annals of Pharmacotherapy Web site today. The article described forty-five cases of FQ toxicity involving the peripheral nervous system, such as tingling, numbness, weakness, burning pain, twitching, or spasms. In addition, 93 percent of the subjects sustained adverse side effects involving other systems: 78 percent experienced central nervous system (CNS) symptoms such as dizziness, agitation, impaired cognitive function, intractable insomnia, or hallucinations; and 73 percent reported musculoskeletal symptoms such as joint or muscle pain or tendon rupture. In many cases, toxicities also involved the cardiovascular and gastrointestinal systems, skin, and sight or hearing. The age of subjects in my survey ranged between eleven to sixty-eight years old, with an average age of forty-two. The great majority of the cases of FQ toxicity were severe, lasting three months in 71 percent and exceeding one year in 58 percent of cases. In 62 percent of these cases, subjects had no other medical disorder except an infection (sinusitis, prostatitis, or urinary infection) that led to FQ treatment. In other words, these people were mostly young, healthy individuals-- until FQ therapy.

The media jumped on my article and wrote about it in newspapers and magazines. My telephone rang a lot. I spent a few minutes on NPR''s Morning Edition with Bob Edwards. Within days, the CDC announced it was dropping Cipro as the favored antibiotic for anthrax exposure and now recommended much safer antibiotics, such as doxycycline. ANTHRAX OR CIPRO? I wish I could say that was the end of it, but it was just the beginning. Six months later the Washington Post carried a story, "Anthrax Patients'' Ailments Linger." The story described symptoms such as fatigue, exhaustion, joint pain, and memory problems lingering in some postal workers. The article pointed its finger at anthrax exposure, but I suspected many of the cases were from Cipro toxicity.

Five days later, the United Press International posted "Anthrax Ills Mirror Cipro Side Effects" on its website: Doctors treating several survivors of last year''s anthrax attacks describe a continuing set of symptoms that are similar to reported side effects of the main drug used to treat them. Side effects include joint pain, fatigue, confusion, difficulty concentrating, and memory loss. "They all fit, right down the line," said Dr. Jay S. Cohen. He said Cipro and other fluoroquinolone antibiotics are well-documented as sometimes causing psychiatric and neurological side effects, as well as musculoskeletal problems. Doctors following these cases do not know whether the problems suffered by the handful of anthrax survivors are related to Cipro or from anthrax. "It is an interesting possibility," said Dr.

Mark Galbraith, an infectious disease specialist in Virginia who is treating one survivor. He discontinued Cipro for his fifty-nine year old patient after two weeks because of a rash and painful joints. Months later, joint pain and difficulty persist. The CDC acknowledged that a percentage of patients did not continue their Cipro because of side effects including joint pain, dizziness, nausea, fatigue, or diarrhea. "A lot of people did stop taking it," said American Postal Workers Union spokeswoman Sally Daridow. The organization has asked Congress to investigate how Cipro and other antibiotics might affect workers long-term. Congress never did, so in 2004 I sent a letter to Congressman Rush Holt of New Jersey, asking for an investigation. Nothing materialized.

In December 2001, the American Spectator published the following in Ben Stein''s Diary: We [Stein and another person] talked for a long time about the anthrax threat in D.C. and then about the medicine of choice, Cipro, that''s being prescribed for it. Just by fate, I had been given Cipro a few weeks before and had suffered simply horrible, dreadful, unbelievably bad psychological side effects: dread, suicidal thinking, panic. In fact, I had the first real panic attacks I had endured since I stopped taking benzodiazepines about twelve years before. I had been mystified about what was causing them until I looked up Cipro in the paperback edition of the Physicians'' Desk Reference, only to find that high among the list of side effects are "abnormal fear" and "dread." My doctor pooh-poohed these effects, but when I stopped taking the Cipro, the effects disappeared pronto. The suddenness of Stein''s reaction and its severity are typical of many accounts of FQ toxicity.

In my study, 58 percent of patients developed reactions within three days of starting a FQ. Also, 70 percent had symptoms like Stein''s involving the central nervous system, such as severe agitation, panic, impaired thinking, hallucinations, suicidal ideation, insomnia, and "brain fog." Typically, Stein''s doctor dismissed the reaction, although there were no other credible explanations for his symptoms. His doctor''s ignorance wasn''t anything unusual, either. At the same time, the health editor of a national magazine wrote that a thirty-day course of ciprofloxacin "wouldn''t cause a healthy adult much harm." Fortunately, Stein''s toxic reaction cleared quickly. He was one of the lucky ones. THOUSANDS SEEKING HELP After publishing "Peripheral Neuropathy Associated with Fluoroquinolone Antibiotics," I began to receive letters and emails.

This one arrived a few months later, in early 2002, from a bioengineer at a local biotech company: I am a thirty year old female with no medical problems before I was given Cipro for a suspected urinary tract infection in March 2002, though my culture came back clean later. I took Cipro for only three days and have been having muscle, tendon, and joint pain since. I was so devastated last week while reading emails from an adverse drug reactions forum, since most of them are saying that the symptoms would go on for years and years. I almost cried on the way home from work as I was driving by the beach and worrying I might never be able to run along the shore again. What''s troublesome about this whole situation is the lack of awareness of the doctor about this problem. Like many cases in your paper, my doctor too dismissed the idea that my symptoms have anything to do with Cipro and no one warned me of anything before I took it. I do wish that, one day down the road, people could at least get a warning from their doctors before they took the medicine. I f.