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Abandoned drugs may be used again

Tue., July 20, 2010

WASHINGTON – More than half a century ago, when antibiotics were transforming modern medicine, a now almost forgotten drug was hailed as something close to the miracle of miracles.

Doctors rushed to prescribe it for an array of medical problems – that is, until they discovered that the drug, chloramphenicol, sometimes had lethal side effects.

Yet today, improbable as it may seem, an effort is under way to revive the use of chloramphenicol and other antibiotics that had largely been banished because of their potential danger.

How can this be?

Some scientists say the older antibiotics may be one way to fight sometimes deadly bacteria that have become resistant to modern drugs.

“People are going all the way back to the original antibiotics that were shelved because of toxicity. We are desperate,” said John S. Bradley, a pediatric infectious disease specialist at the UC San Diego School of Medicine.

The impulse to re-examine the older antibiotics is all the stronger because relatively few new antibiotics are in development. And, because the old ones have not been heavily used in recent years, bacteria have not had much chance to develop resistance to them.

For example, one drug maker says in-house studies bolster evidence that chloramphenicol, a drug from the 1950s, is effective against methicillin-resistant Staphylococcus aureus, or MRSA, which killed an estimated 15,000 people in 2008.

Rifampin, a 1960s-era drug used to treat tuberculosis, is now sometimes employed in combination with other antibiotics to treat MRSA, Bradley said.

Colistin, a drug from the 1940s, is being used to treat resistant strains of acetinobacter and other pathogens collectively known as Gram-negative bacteria.

The challenge is figuring out ways to manage the possible side effects of the older medications and weigh the risks of administering them.

Philadelphia-based Lannett Co. says it will ask the Food and Drug Administration to approve chloramphenicol for use against MRSA.

“It works,” said Arthur Bedrosian, chief executive of Lannett. “We want to see if FDA will allow use of it as a drug of last resort.”

Chloramphenicol is still used overseas to treat meningitis and other ailments. It has been largely absent from the U.S. market for decades, although an injectable version is still available, according to federal records.

The FDA declined to comment on Lannett’s plans to seek approval for a capsule version of chloramphenicol as a MRSA treatment.

But Dr. Edward Cox, head of the agency’s Office of Antimicrobial Products, said that “studying previously approved drugs for the treatment of patients with infections caused by resistant bacteria may provide useful data to assess their utility in treating these infections.”

When first introduced, chloramphenicol was a huge seller because, unlike other early antibiotics such as penicillin and streptomycin, it effectively attacked a range of pathogens and, in the early going, showed relatively few side effects.

But as it became more widely prescribed, doctors linked it to aplastic anemia, a potentially fatal illness in which the bone marrow produces insufficient quantities of new blood cells.

Estimates of the incidence of the illness range from 1 in 10,000 users of chloramphenicol to 1 in 80,000, according to Thomas Maeder, author of “Adverse Reactions,” a history of the drug’s development, marketing and eventual decline.

“That is not tremendously high, but that assumes you’re giving it to someone who needs it,” Maeder said.

Bedrosian said he’d be willing to market chloramphenicol with a so-called black box warning about possible fatal side effects, a labeling drug makers normally resist strenuously.

“If you’re going to die anyway, you may as well try it,” Bedrosian said, referring to patients with severe MRSA infections. “This is a second or third line of defense if nothing else is working.”


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