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Researchers are finding an increase in the number of antibiotic-resistant infections in humans that can be traced through the food supply to the use of such drugs on livestock and poultry. Salmonella resistance to fluoroquinolones is the latest to emerge and also qualifies as among the most worrisome, according to investigators who spoke during a symposium, ``Antibiotics in Plant and Animal Agriculture,'' at the annual meeting of the American Association for the Advancement of Science, held in Washington, D.C., in February.

About half the antibiotics used in the United States are for treating human infections, while the other half are used in agriculture, both for treating infections and for promoting growth in beef cattle, swine, and poultry. Sometimes this agricultural use is intense. For instance, chickens typically spend 42 of their 45 days of life on antibiotics, according to Fred Angulo of the Centers for Disease Control and Prevention in Atlanta, Ga. ``It's hard to conjure up a more effective means'' of selecting for antibiotic resistance, he says. Farm-generated resistance does not stay put. ``We live in one ecosystem, and the genes just flow through the system,'' he says.

Fluoroquinolone antibiotics are widely used in human medicine, and when they were approved for treating chickens in 1995, scientists predicted that pathogens with resistance to these antibiotics would soon be causing human infections. For instance, Campylobacter spp., the most common cause of bacterial foodborne illness, are found in 60 to 80% of chickens in U.S. supermarkets. By 1998, tests indicated that 20% of those birds carried fluoroquinolone-resistant Campylobacter strains. As predicted, pathogens with fluoroquinolone resistance also began to turn up in humans. In 1999, 20% of human Campylobacter infections were fluoroquinolone resistant, up from 13% in 1998. Investigators find a similar pattern in Europe.

Fluoroquinolone resistance in Campylobacter spp. typically results from a single point mutation. In Salmonella, by contrast, resistance to this antibiotic depends on mutations occurring in two independent genes. Scientists have already detected Salmonella with one of the mutations and with a decreased susceptibility to fluoroquinolones.

Adding to this concern is multiple drug resistance that occurs in the widespread Salmonella serotype Salmonella enterica serovar Typhimurium Definitive Type 104 (DT104). This strain can be resistant to members of five antibiotic classes: ampicillin, chloramphenicol, streptomycin, sulphonamides, and tetracycline. Researchers worry that fluoroquinolones might soon join this list. During a recent outbreak of DT104 in Denmark, for instance, a patient died despite being treated with fluoroquinolones.

The subtherapeutic use of antibiotics to promote animal growth is one area Angulo and many other public health experts would like to see eliminated or at least substantially reduced. Last year Europe prohibited such use for antibiotics also used in human medicine. While Europe allows only two antibiotics to be used as growth promoters, in the United States 17 antibiotics are allowed for this purpose, according to Angulo, including 6 that are also used for treating infections in people. Of particular concern is the use of chlortetracycline, oxytetracycline, and penicillin on animals, he says. All developed countries except the United States and Canada long ago terminated animal use of these key antimicrobials used in human illness. ``It's quite a sad failure,'' he says.

Exactly how antibiotics improve livestock growth is still unexplained, says Lester M. Crawford of Georgetown University, Washington, D.C., and formerly with the Center for Veterinary Medicine at the Food and Drug Administration, who also spoke during the meeting. Approximately 40% of all antibiotics in the United States are used in animals, but this does not mean that this usage contributes 40% to antibiotic resistance in humans. ``Obviously, most antibiotic resistance affecting humans would come from the human usage of antibiotics, but the precise contribution of agricultural uses has not, and perhaps cannot, be characterized,'' he says.

But there are alternatives. Poultry producers in Denmark have demonstrated that chickens can be cost effectively raised without use of antibiotics as growth promoters (see p. 264), although Crawford says some drugs that are used in neither human nor veterinary medicine can be acceptable for use as growth promoters. Rather than completely eliminating the use of antibiotics for this purpose, as Denmark and Sweden have done, ``we should do it selectively,'' he says.

Inappropriate farm use of antibiotics is not the only culprit behind the increases in microbial resistance--parents and pediatricians who insist on antibiotics for viral ear and respiratory infections also play a big part. Still, Angulo says, the already worrisome trend of antibiotic resistance from use on food animals ``could become a monumental problem, and it needs to be controlled before it gets out of hand.''

Christine Mlot
Christine Mlot is a science writer in Madison, Wis.