A new study shows that overuse of a drug used to prevent and treat malaria may be contributing to growing antibiotic resistance. Researchers report in the journal PLoS ONE that Escherichia coli bacteria resistant to the antibiotic ciprofloxacin were detected in the digestive tracts of villagers from remote rainforest communities in Guyana who had been given the drug chloroquine to prevent and treat malaria, a potentially fatal disease spread by mosquitoes. This is the first study to show that resistance can emerge in individuals never exposed to the antibiotic, which is used throughout the world to treat bacterial infections, including pneumonia, urinary tract infections and sexually transmitted diseases.
"Ten to 15 years ago, resistance to ciprofloxacin was rare. [Now], outside of remote populations, cipro resistance in hospitals and the community at large is becoming a problem," says Andrew Simor, a senior scientist at the Sunnybrook Health Sciences Center at the University of Toronto, who was not involved in the study. "E. coli is one of the most common causes of infections in humans. A decade ago it was nearly universally susceptible to ciprofloxacin." Today, he says, as many as 30 percent of hospital patients tested have E. coli that failed to respond to ciprofloxacin, which is the drug of choice for treating these bacteria.
Drug-resistant bacteria are known to arise from the overuse of antibiotics, which is why researchers were surprised to discover that they can develop in areas that do not have access to ciprofloxacin, says study co-author Michael Silverman, an infectious disease specialist at Lakeridge Health Network in Ontario. In fact, he says, ciprofloxacin-resistant E. coli were even more widespread in remote Guyanese villages than in U.S. intensive care units "where every second person is on antibiotics."
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During a three-year study, the researchers monitored the levels of antibiotic-resistant E.coli in patients at their clinics. They found that rates of resistance were over three times higher in February 2003 than they were just a year earlier, Silverman says. The jump corresponded to the increased use of chloroquine—a drug widely prescribed to prevent and control malaria —after a large outbreak of the disease (which causes high fevers, chills, nausea and headaches) in late 2002.
Chloroquine, taken daily by some villagers, is a close chemical cousin of ciprofloxacin. In the early 1960s, the creation of the antibiotic class (quinolones), which includes ciprofloxacin, was based on the by-products of chloroquine synthesis. In laboratory experiments, the team confirmed that chloroquine concentrations similar to those seen in the human intestinal tract prompted E. coli ciprofloxacin resistance.
These findings may have far-reaching implications for the escalating problem of antibiotic resistance. The worldwide use of ciprofloxacin pales in comparison with the use of drugs to counter malaria, which the U.S. Centers for Disease Control and Prevention estimates strikes 350 million to 500 million people (mostly in Africa, Asia, and Central and South America) annually. "It is very possible that the antimalarial drugs may be inducing a large amount of the antibiotic resistance that occurs in the tropics," Silverman says.
John Turnidge, chief of laboratory medicine at Women's and Children's Hospital in North Adelaide, Australia, called the study "fascinating," noting that he has long suspected that the overuse of antibiotics was not the only cause of bacterial resistance. This shows, he says, that certain drugs such as chloroquine (which works by targeting the parasites inside red blood cells) may drive resistance to other classes of drugs such as the antibiotic ciprofloxacin.
Traditionally, scientists have targeted viruses, bacteria and parasites in different ways and assumed that the treatments had little to do with one another. But this finding indicates that one may play off the other when it comes to encouraging resistance in human pathogens.
Christopher Plowe, an infectious disease specialist at the University of Maryland Medical Center, says more study is needed to determine whether health officials should reconsider the widespread use of chloroquine to battle malaria. Researchers plan to test the effect of antimalarials other than chloroquine to determine if they can do as effective a job without also hobbling the power of ciprofloxacin.
Silverman stressed that the study highlights the need to continue to try to prevent malaria through the use of insecticide-treated bed nets, along with the development of an effective vaccine.