Side effects undermine anthrax drug adherence

More than half dropped drugs by 30 days

Bioterrorism
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Amid the hype and horror of the 2001 anthrax attacks, it seemed a given that the people potentially exposed would be particularly diligent in completing their antibiotic regimens. But as time passed — and side effects continued or worsened for some — compliance fell off dramatically for many of the 10,000 people put on 60-day regimens for ciprofloxacin and doxycycline, according to preliminary data from the Centers for Disease Control and Prevention (CDC).

None of the people who started on antibiotics have developed anthrax, but the CDC wants some answers on the lack of adherence. To that end, the CDC is conducting a telephone survey project that will attempt to reach all 10,000 people for whom post-exposure antibiotic prophylaxis was recommended. The interviews began in late January and are expected to continue through March 2002. The people were potentially exposed to anthrax in Connecticut, Florida, New Jersey, New York City, and Washington, DC.

"We are making sure we get in touch with all of these people to evaluate how they did in terms of taking antibiotics," says Ian Williams, PhD, medical epidemiologist in the CDC national center for infectious diseases. "We have data showing adherence definitely wasn’t as high as people, prior to this outbreak, would have thought it would be."

The CDC attempted a variety of methods to assess compliance prior to the phone survey, including tracking individuals who did not return to refill their medication. Other methods include giving a sample of those exposed questionnaires that were self-administered, given by a nurse, or by telephone, according to Nancy Rosenstein, MD, medical epidemiologist in the CDC national center for infectious diseases. "In general, adherence has declined over the course of the [first] 30 days to as low as 45%," Rosenstein said at a recent CDC meeting on post-exposure prophylaxis for anthrax.

Some groups were more compliant than others. For example, employees who worked in the American Media Building in Boca Raton, FL, were closer to 70% compliant, she said. But only 45% compliance at 30 days was also found in a "high risk group" of mail handlers in New York City, she added. "Adherence experts tell me that when we actually count pills, the self-reporting numbers probably overestimate real adherence by as much as 20%," Rosenstein said. "So the real estimates of adherence — taking the antibiotics every day — are obviously substantially lower."

In terms of self-reported adverse events, within two weeks of taking ciprofloxacin, 19% were reporting severe nausea, vomiting, abdominal pain, and diarrhea. At 30-day surveys, many people had switched to doxycycline, but self-reported adverse events increased to 45%. Again, the predominant symptoms were severe nausea, vomiting, diarrhea, and abdominal pain. About 12% of the people reporting adverse events required additional follow-up with medical chart review and physician interviews, she said.

"I don’t want to in any way minimize the impact of these symptoms on people’s daily life, but when we actually investigated further, we were unable to identify anybody who actually required hospitalization or an emergency room visit for their adverse events," Rosenstein said.

Thus, based on Food and Drug Administration criteria, no serious adverse events have been linked to taking antibiotics for anthrax exposure. A more complete picture of the adherence problems should emerge from the CDC telephone survey of all recipients. Preliminary surveys have found that 6% to 12% of respondents reported at least missing some of their doses because of the side effects, she said.