Put out to pasture: strategy to prolong antibiotics' potency.

The use of antibiotics to promote growth in farm animals hastens the end of their medical effectiveness, according to a new study.

Using a mathematical model to probe the evolutionary dynamics of bacterial resistance to antibiotics, researchers have found evidence that agricultural use of the drugs accelerates the rise of resistant bacterial strains. In general, concludes coauthor David L. Smith of the University of Maryland School of Medicine in Baltimore, "it's not a good idea to use new drugs in animals until they've already been spent in humans."

Antibiotics are used both to treat sick people and to promote growth among livestock. Both applications fuel the evolution of microbes impervious to the drugs. Debate about whether antibiotic use in livestock should be curtailed to prolong the drugs' effectiveness in people has become more heated over the years (SN: 7/18/98, p.39).

Beginning in the mid-1980s, some European countries began phasing out use of antibiotics as animal-growth promoters, and researchers there have since observed declines in antibiotic resistance in bacteria found in people there (SN: 9/6/97, p.157). In the United States, however, agricultural use of antibiotics is still widespread, and bacterial resistance is increasing.

To better understand how resistance can arise, Smith and his colleagues devised a mathematical model that predicts the evolution of bacterial populations that initially have low rates of resistance to a hypothetical antibiotic. The model specifically considers bacteria, such as the enterococcus gut microbe, that spread easily from person to person. Though generally harmless, enterococci can cause severe illness when they enter wounds, the bloodstream, or urinary tract. In hospitals, where this kind of transfer happens readily, some strains have developed resistance to vancomycin, a clinical antibiotic similar to one fed to livestock.

The model takes into account such factors as how long bacterial populations tend to persist in the human gut, how readily they spread among people, and how commonly a given antibiotic is used in people and on farms. The researchers found that antibiotic resistance becomes prevalent eventually, regardless of whether the drug is used on livestock. However, agricultural use quickens the evolution of such resistance.

These findings have led the researchers to propose limiting agricultural use of a given antibiotic until resistance to it is already widespread in bacteria that infect people. That conclusion is at odds with an alternative tack that the Food and Drug Administration has proposed. It would stop a drug's use for promoting animal growth once resistance of human pathogens to the drug reaches a critical threshold.

The Baltimore researchers' approach to managing resistance could be applied to drugs such as virginiamycin, an antibiotic that's long been used on livestock. It's almost identical to Synercid, which physicians recently began prescribing to patients.

The FDA has an obligation to regulate virginiamycin because there's a reasonable expectation that its continued use in animals will accelerate the evolution of Synercid-resistant bacteria, Smith says. His team's research was partially funded by virginiamycin's manufacturer, Pfizer, headquartered in New York City.

For bacteria such as enterococci, the new study suggests that "the best time to intervene is before there's a noticeable [resistance] problem," says Marc Lipsitch of the Harvard School of Public Health in Boston. Once drag resistance is apparent--"once the horse has fled the barn," as Lipsitch says in an editorial accompanying the new study in the April 30 Proceedings of the National Academy of Sciences--there may be little point to shutting the door on agricultural use.

However, with new drugs being derived from existing classes of antibiotics, giving animals a drug after it's no longer effective in people still poses a public health risk, cautions Stuart B. Levy of Tufts University School of Medicine in Boston. That's because resistance to one drug in a class may make bacteria resistant to related drugs, as well.