Cure May Be Health Hazard

TIMES HEALTH WRITER

Anthrax anxiety has spawned a massive public health experiment--one that is unplanned, uncontrolled and perhaps unstoppable.

Never before have so many healthy people been given private stashes of antibiotics to use at their whim.

The trouble, say medical experts, is that indiscriminate prescription of Cipro and other powerful antibiotics could prove horribly counterproductive. It could ultimately render these last-defense drugs helpless against serious bacterial infections, allowing them to flourish and spread to others.

Even those who don't take Cipro could develop infections resistant to it.

But in a nation with powerful faith in the ability of drugs to treat any ill, patients are besieging doctors with requests for Cipro and other powerful just-in-case antibiotics. Unsolicited e-mails from online pharmacies fan their fears.

"With the threat of anthrax upon us, we are now offering Cipro to help build your immune system to fight the anthrax virus!" a mass e-mail proclaims.

Even trusted figures such as NBC News anchor Tom Brokaw are lending encouragement. "In Cipro we trust," he said Monday night at the close of his newscast. His personal assistant contracted cutaneous anthrax--on her skin--when she handled a contaminated letter addressed to Brokaw.

Many doctors are bending to patients' pressure, to the dismay of some colleagues. "Patients are getting angry," said Dr. Samuel Fink, a Tarzana internist who has drawn fire for saying no even to family members. "They're calling and they're demanding 60 days of Cipro for themselves, their wives and their dogs."

At the very least, the run on Cipro will aggravate a growing problem with antibiotic resistance that was flagged as a serious danger years before the terrorist attacks.

Many Americans use antibiotics inappropriately, taking them for shorter periods than prescribed or for viral infections instead of bacterial infections. They don't kill viruses.

Over time, this misuse leads to development of hardier bacteria and more virulent infections.

With antibiotics in their personal medical cabinets, patients will be tempted to use the pills, unsupervised, when they are scared or they develop flu-like symptoms that mirror the initial signs of anthrax.

"These pills are not going to sit on the shelves. They're going to be used, especially if you spent $250 on them," said Dr. Stuart Levy, a professor of medicine at Tufts University and president of the Alliance for the Prudent Use of Antibiotics. "It's a mistake to stockpile."

Dr. Jane Spiegel, a Santa Monica internist, agreed.

"What we're going to see is a public health nightmare in the making," she said. "When you have ready availability of antibiotics, people are going to have their runny nose or a little cough, and they're going to say, 'I'll just take a few of these Cipro and it'll help me out.'

"If that happens, we're going to have massive resistance. We won't have anything left in our armamentarium. That's our big gun."

The U.S. Food and Drug Administration has strongly recommended that physicians not prescribe Cipro for individual patients to have on hand for possible use against anthrax precisely because of fears about development of drug-resistant organisms.

The reason Cipro is so popular is that it is the only drug approved by the FDA for treatment of inhalation anthrax (although a few other antibiotics work too). The infection is more than 90% fatal if not treated early.

Health experts have repeatedly told the public that the federal government has enough antibiotics for 2 million people in case of a major anthrax attack, and doses for 10 million more are requested. But such assurances are doing little to calm patients' nerves or cause doctors to say no.

Demand for Cipro has become so intense that drug wholesalers are now rationing supplies, and some pharmacies in Southern California are limiting patients to a fraction of what is recommended in the event of a confirmed anthrax infection.

At Ocean Park Pharmacy in Santa Monica, prescriptions have come from more than 50 doctors, owner Robert Rosen said. That has forced him to limit prescriptions to 20 500-milligram pills. In fact, the actual recommendation in cases of anthrax exposure is 120 pills.

"I don't see any doctor saying no, but I find that certain doctors are giving smaller doses than requested," Rosen said. "People want hundreds and hundreds. Some people want to have 300 or 400 in their house. I think it's foolish."

Cipro is a member of the antibiotic class called fluoroquinolones. These drugs are considered the last line of defense against some of the most difficult-to-treat infections, such as pneumonia, severe sepsis and blood-borne infections in hospitals. The category of drugs is also popular for treating urinary tract infections and upper respiratory infections.

If Cipro became ineffective against urinary tract infections, physicians would be left with few other choices. In fact, patients may need to be hospitalized in order to receive more powerful intravenous antibiotics at an extremely high cost.

Well before Sept. 11, antibiotic resistance was already limiting physicians' choices for dealing with certain bacterial infections:

* The New England Journal of Medicine published a study this month identifying a strain of E. coli bacteria that is resistant to some antibiotics for urinary tract infections. Researchers became concerned because they saw an increase in bladder infections among college women in Berkeley, Minneapolis and Ann Arbor, Mich.

The women's infections were caused by bacteria resistant to trimethoprim-sulfethoxazole, a popular combination sold under the brand names Bactrim or Septra. The next line of defense is Cipro.

* In April, the British medical journal Lancet reported that five patients had developed resistance to linezolid, introduced last year, which is the first new antibiotic in almost three decades. The drug is used against the so-called superbug Staphylococcus aureus, which can cause lethal infections, often in hospital patients.

* The FDA last year proposed detailed labels on all antibiotics warning about the dangers of resistance.

Bacterial resistance to an antibiotic can take years to develop, but it can be passed from person to person through everyday interactions. Anthrax infections, however, are not contagious.

Large-Scale Misuse Would Be Harmful

Resistance can't be detected until at least a day or two after a person is tested for an infection, but by that time, a doctor usually has put the patient on an antibiotic already. Once enough patients develop infections resistant to an antibiotic, doctors abandon it. Some bacteria are resistant to more than one drug.

Large-scale resistance is unlikely to develop if people here and there take Cipro inappropriately, but the chances increase as the number of patients using it improperly grows.

If "all of a sudden, everybody grabs their Cipro," said Dr. Peter Katona, an assistant professor of clinical medicine at UCLA, "all of a sudden, you have a huge, huge issue."

In parts of Southeast Asia, for instance, 60% of E. coli bacteria are resistant to Cipro and other fluoroquinolones because of the widespread availability of the drugs, said Levy of Tufts University.

"We're going to end up with a situation akin to other parts of the world where fluoroquinolones are going to be used indiscriminately," Levy said. "We're not going to have it to use" for life-threatening infections.

Some researchers say it is too soon to draw conclusions about resistance to Cipro, although they too are worried.

"The overuse of antibiotics for colds and bronchitis has been documented consistently over the past 20 years. We know that's a very real concern," said Dr. Ralph Gonzales, an associate professor of medicine at UC San Francisco who heads a group of doctors trying to prevent overuse.

Gonzales said he plans to study the effect of the anthrax scare on doctor visits and antibiotic prescriptions for respiratory infections this winter. "This will give us a glimpse into human behavior and physician behavior in response to the terrorist attacks," he said.

Part of the problem with Cipro, doctors and pharmacists say, is that well-known people continue to cite the drug by name. Each time an envelope containing anthrax is found, dozens or hundreds of people in the area are given Cipro as a precautionary measure until tests can determine who has been exposed to the bacteria. Brokaw's remark only added to the buzz.

He and other NBC employees were prescribed the antibiotic last week after his assistant was infected.

"Credible people are telling the public that there's a serious threat," said Rosen of Ocean Park Pharmacy. "That makes even the more legitimate people concerned."

Some doctors are furious at their colleagues for giving in to public fear and prescribing Cipro from demanding patients. They say these doctors are unprofessional and irresponsible.

In addition to resistance concerns, Cipro has potential side effects. It can, for example, impair the development of children's knees and other weight-bearing joints. It can also cause kidney problems in children and adults.

The drug can be fatal if taken with theophylline, a drug prescribed for asthma and some other respiratory conditions. Dr. Jon Rosenberg, a medical epidemiologist with the California Department of Health Services, said he received a chain e-mail this week suggesting that people start taking Cipro if those around them develop colds or the flu. Such advice runs counter to medical expertise.

California and its medical association had, as it happened, designed a program to reduce antibiotic use before the terrorist attacks. The kickoff announcement was planned for Sept. 13 but was postponed indefinitely because of the attacks.

For the short term, Levy said the public health community may need to amend its message discouraging the stockpiling of Cipro, and insert another message for those who already have it.

"It's not a good idea to stockpile, but if you've done it already, at least make a promise to yourself and to your neighbors that you're not going to take it unless there's a public health alert," Levy said. "This is not a casual situation."

*

Times health writer Sharon Bernstein contributed to this report.

(BEGIN TEXT OF INFOBOX / INFOGRAPHIC)

How Drug Resistance Occurs

Antibiotic resistance occurs when bacteria find ways to survive despite the drug's presence. Below are factors that contribute to resistance and ways to avoid it.

Factors

* Misuse and overuse of antibiotics.

* Demand for antibiotics when they are not appropriate, such as for viruses.

* Failure to finish an antibiotic prescription. When this happens, hardier bacteria that have not been killed can restart an infection.

* Availability of antibiotics without a prescription in some countries.

Avoiding it

* Do not demand antibiotics from your physician.

* When given antibiotics, take them as prescribed and complete the full course of treatment.

* Do not hoard pills for later use or share leftovers with other people. Partial doses can actually make the bacteria resistant and stronger.

* Wash your hands properly with soap to reduce the chance of getting sick and spreading infection.

Source: Alliance for the Prudent Use of Antibiotics

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