July 16, 2008

Malaria Drug May Cause Antibiotic Resistance

Canadian researchers said on Tuesday that people in remote villages in South America who were treated with a common malaria drug, show high levels of resistance to a widely used class of antibiotics known as fluoroquinolones, despite never having taken the drugs.

The researchers said the finding suggest that treating malaria with the cheap, widely used drug chloroquine "” a close cousin of fluoroquinolones "” may boost the risk of resistance to these antibiotics.

Dr. Michael Silverman of Lakeridge Health Centre in Oshawa, Ontario, said fluoroquinolones or quinolones are among the most commonly used antibiotics in North America and Europe.

"Loss of these drugs would be a major blow to public health," said Silverman.

During humanitarian medical visits between 2002 and 2005, he and colleagues studied people in extremely remote villages in the Guyanese rain forest.

He said the population had never been exposed to fluoroquinolones, and thus represented a unique population to study antibiotic resistance, thought to be linked with the overuse of antibiotics. He had expected to find none.

Instead, they found 4.8 percent of people studied had strains of E. coli that were resistant to the antibiotic ciprofloxacin, the generic name for Bayer AG's drug Cipro, and one of the most popular fluoroquinolones.

"A resistance rate of 4.8 percent is especially high considering that a 2003 study published in the Journal of the American Medical Association found a 4 percent resistance rate in intensive care units in North America, where the drug is widely used, " said Silverman.

He said that tests of local water samples confirmed that no antibacterial agents were found in the drinking water, but chloroquine, used to fight malaria, was present.

To confirm that chloroquine could cause resistance, the researchers combined the drug with bacteria in the lab and found that it had a weak antibiotic effect. It was not enough to kill the bacteria, but enough to develop resistance.

Resistance to Cipro could extend to newer drugs in the class such as Johnson & Johnson's Levaquin or levofloxacin and Bayer's Avelox or moxifloxacin, according to Silverman.

"We tested for Cipro because that is still the most widely used, but we know any bacteria that is resistant to one is resistant to all," he said.

The findings could have implications for a new generation of malaria therapies known as artemisinin-based combination therapies, or ACT drugs, which are recommended by the World Health Organization because of growing resistance to older treatments such as chloroquine.

Silverman said ACT therapies usually include quinoline drugs similar to chloroquine. "The question is, 'Is this true of all quinolines or just chloroquine?'"

This helps explain high rates of resistance to fluoroquinolones in tropical regions, he added.

"What we have to do is redouble our efforts to prevent malaria, so we can use less of these drugs," he said.

Malaria, caused by a parasite carried by mosquitoes, kills more than 1 million people a year worldwide.

The study appears in the journal PLoS One.


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