Resistance to Important Antibiotic May Develop in Soil, Study Shows

November 26th, 2012

Food Safety News
By Gretchen Goetz

Over the past two decades, scientists have been tracking a concerning rise in bacterial resistance to cephalosporins – a class of antibiotics used to treat a variety of human infections. Now, a study out of Washington state reveals that the solution to this problem might lie in the way farmers treat animal waste.

The research, published this month in PLOS ONE, shows that the source of cephalosporin resistance likely lies in soil, where bacteria is exposed to feces and urine from animals treated with these drugs.

The link between cephalosporin resistance and use of the drug in animal agriculture has long been suspected. In April of this year, the U.S. Food and Drug Administration published a rule limiting the use of cephalosporins in food animals.

“FDA is concerned that certain extralabel uses of cephalosporins in cattle, swine, chickens and turkeys are likely to contribute to cephalosporin-resistant strains of certain bacterial pathogens,” noted the agency in its announcement of the rule.

But one piece of the puzzle has been missing: where is this resistance developing? Animals treated with ceftiofur – a cephalosporin – don’t excrete bacteria that’s resistant to the drug, meaning resistance doesn’t appear to develop in the animal’s gut. That’s why researchers at Washington State University turned to soil containing waste from animals treated with the cephalosporin to see if resistance was developing there. And their hunch turned out to be correct.

“Bacteria in the soil are basically eating the drug for breakfast,” said Doug Call, professor of molecular epidemiology at WSU’s Paul G. Allen School for Global and Animal Health and an author of the study.

Then, after being exposed to cephalosporin, the stronger, drug resistant bacteria that survive easily colonize in animals, the study shows.

“If you’re excreting it onto the ground and you’re amplifying resistant bugs there, then the animals are basically reinnoculating themselves from contact transmission,” Call explained in an interview with Food Safety News.

This process is sped up in warmer months, researchers found, when higher temperatures cause the drug to degrade more quickly.

“In the lab at room temperature, 24 hours is plenty to set up the whole bias for resistant organisms,” Call said. “One day and it’s over.”

These findings suggest that, if soil containing cephalosporin residues can be prevented from coming into contact with animals before bacteria has had time to develop resistance, the spread of cephalosporin-resistant plasmas could be prevented, and the effectiveness of this class of drugs in human medicine could be preserved.

“You could potentially stop that selection [among bacteria] on the ground using a different strategy in animal husbandry, using a different strategy in how you handle waste,” explains Call. “There may be ways to basically neutralize or immobilize these drugs so they cannot act biologically on the bacteria. Or it may be something as simple as cleaning out the manure right away or the urine as fast as you can.”

Another possible solution may be isolating sick animals from healthy ones, he said, since cephalosporin is predominantly used to treat sick animals, and that is the only use now allowed by FDA.

The bacteria scientists looked at in this study was E. coli, which isn’t treated with cephalosporins in human cases; however, Call said the plasma that carries the resistance trait is easily transmitted among all gram-negative gut bacteria, including Salmonella and Shigella.

“These newer cephalosporins are the antibiotics of choice in the treatment of serious Salmonella and Shigella infections, particularly in children,” noted FDA in its Q & A sheet on cephalosporin prohibition.

An increase in cephalosporin resistance among Salmonella has been well-documented by the National Antimicrobial Resistance Monitoring System (NARMS). In 1997, no Salmonella found in cattle or swine were resistant to ceftiofur (a drug in the cephalosporin class). By 2009, 14.5 percent of Salmonella isolated from cattle were resistant to ceftiofur. For swine that figure was 4.2 percent. Over that same time period, ceftiofur resistance had grown from .5 percent of Salmonella found in chickens and 3.7 percent of Salmonella found in turkey to 12.7 percent and 12.4 percent, respectively.

At least five foodborne illness outbreaks were linked to cephalosporin-resistant Salmonella between 2001 and 2009, according to data collected by the Center for Science in the Public Interest. A total of 200 illnesses, 40 hospitalizations and 1 death occurred as a result of these outbreaks.

But before the results of this study can be applied to curbing resistance among dangerous pathogens, the next step is to replicate the results under field conditions, said Call.

“Everyone’s going to criticize a study like this, and rightfully so,” said Call, “in that it’s limited in scale and scope because it’s on a lab bench, even though we did use materials originating from the dairies and directly from the cattle.”

Call said he fully expects that these results would be duplicated in a farm setting.

If and when it comes time to look at on-farm interventions, cost will be the biggest consideration for farmers, he noted.

“If you can replicate [these findings] which, to be honest with you, I don’t see why you couldn’t, then the next question is is there a way to start controlling the problem that could be applied in an economical, cost-effective manner? If you can find solutions like that, everybody wins. You preserve selection, you preserve the ability to use these drugs and you hopefully don’t cost producers much of anything. That’s what we’re after really is that kind of a solution.”

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