Bacteria containing a gene that confers resistance to a crucial class of antibiotics have been found in buildings on a pig farm in the midwestern United States, a troubling and mysterious discovery that should ring a warning bell over farm antibiotic use.
The discovery is troubling because the drugs to which the bacteria are resistant are so important. Called carbapenems, they are one of the few drug families that still work against deadly, multi-drug-resistant hospital infections. Carbapenem-resistant bacteria, known as CREs, are considered an “urgent threat” by the Centers for Disease Control and Prevention.
The discovery is mysterious because carbapenems are not used on that farm; in fact, they are not used in agriculture anywhere in the world. So the resistance may have been transported onto the farm in a manner no one can yet explain.
But there’s no question that the discovery is alarming. It’s likely to bring fresh scrutiny to the use of antibiotics on farms in the US, just as a long-delayed set of FDA restrictions on farm use is finally clicking into place.
The discovery was announced Monday in the journal Antibiotic Agents and Chemotherapy, by a team at Ohio State University led by Thomas Wittum, who chairs the department of veterinary preventive medicine. His group was tracking the occurrence of resistance to a different set of drugs called cephalosporins, which are widely used in swine production, when they unexpectedly found a rare carbapenem-resistance factor known as IMP.
“We weren’t expecting this and we were quite surprised,” he told me. “We had predicted that the common CREs in U.S. healthcare would be the ones we would first start to see in animals, but this is a really unusual one.”
The discovery is not the very first CRE found in livestock in the U.S. Last January, a group of researchers mostly from Texas Tech University found CREs in dairy cattle in New Mexico and Texas. But this second finding is more worrisome than the first, because the resistance in the pig-farm bacteria was contained on a plasmid, a piece of DNA separate from the bacterial chromosome that can migrate between bacterial species, and thus spread resistance quickly.
“This plasmid seems especially mobile; we got it out of a whole lot of bacterial organisms on the same farm,” Wittum said.
The farm where the resistance was found, which Wittum didn’t want to identify, is what is called a farrow-to-finish facility, one on which pigs spend their whole lives. It has 1,500 sows and is a “closed” farm, meaning no animals have been added to the herd from the outside, for more than 50 years. (The farm buys semen for artificial insemination.) On a farrow-to-finish farm, pigs are born in a farrowing building, weaned and moved to a nursery building at three weeks of age, and then live to about six months in a finishing barn.
On this farm, piglets get a dose of the cephalosporin antibiotic ceftiofur (related to the common human-use antibiotic rocephin) when they are born, and male pigs get a second dose when they are castrated a week later. Wittum’s team was looking for cephalosporin resistance by swabbing interior surfaces of the farm buildings and taking fecal samples from the pigs.
When they spotted the IMP in their samples, they went back for more samples, making four visits altogether between July and November 2015. Out of 109 samples taken from surfaces in the farrowing and nursery barns, 18 possessed resistance to multiple antibiotics and to carbapenems as well.
But the team did not find any CRE in the finishing barn, where the pigs spend the last part of their lives before being sold, nor in any fecal samples taken from pigs in any of the barns. Since then, however, they have gone back, retested sows and piglets, and found them carrying IMP in their feces — which raises the possibility these highly-resistant organisms could move with pigs when they leave the farm, and could enter the food chain.
“The larger significance is that we now know these really important, highly multi-drug-resistant organisms are present in agriculture, that threatens the health of animals,” Wittum said. “But also there are public-health implications, because of the potential for these to be transmitted unknowingly to people, where they might colonize the enteric flora of consumers and produce problems some time in the future.”
Other researchers who work on antibiotic use in agriculture said this discovery is very important.
“If they can find this in one farm, and not a huge farm, over and over, then there is probably more of this out there than we realize,” said Tara Smith, a molecular epidemiologist at Kent State University who was the first researcher to identify MRSA, drug-resistant staph, in pigs in the United States.
If carbapenem resistance is spreading in agriculture, she pointed out, we probably won’t know — because the limited testing of animals and meat that occurs in the United States looks for antibiotic resistance only in foodborne organisms such as salmonella and campylobacter. The organisms that Wittum and his co-authors recovered from the barns were random gut bacteria that linger on environmental surfaces: E. coli, citrobacter, morganella and providencia.
Much more comprehensive surveillance is crucial, said Lance Price, a microbiologist and the founder of the Antibiotic Resistance Action Center at George Washington University. Because carbapenems are not used in agriculture, the source of the resistance that Wittum’s team found is perplexing. One possible explanation is that is was somehow transported into pigs by human contact, and then burgeoned in the pigs under the influence of the cephalosporin drugs they were given; cephalosporins and carbapenems have related molecular structures.
“We think from a public-health standpoint of the risks of antibiotic use in animals being the spread of resistant bacteria from animals to people, the environment, or food,” said Price, who showed in earlier research that “livestock MRSA” — a strain of drug-resistant staph that arose in pigs and spread to humans and into the food supply — actually originated in humans, and gained resistance when pigs were given farm antibiotics.
“But we have to think about bidirectional spread between people and animals,” he said. “People carrying the more important strains of CRE into these swine houses and transmitting them to animals, and then their being amplified under the influence of antibiotics.”
Whether and how to use antibiotics in farm animals and how much risk it poses to humans is a hot policy issue in the U.S. right now. January 1 marks the final implementation of FDA rules that phase out growth promoters — micro-doses given to meat animals to increase their weight — and also shift the responsibility for farm antibiotic use from individual producers to veterinarians.
But the drug use on the farm where Wittum’s team found CRE was not growth promotion; it was preventive use, which is still allowed under the new rules. David Wallinga, a physician and senior health officer at the Natural Resources Defense Council, said that should prompt closer scrutiny of all antibiotic use on farms.
“The pattern we see with enormous antibiotic use in livestock, including pigs, is: ‘Oh, that’s not a problem,’” he said. “And then the next stage is, ‘Well, it’s hypothetical that’s a problem.’ And then, ‘Well, it might be a problem in the United States, but people aren’t dying yet.’ And the last stage is, ‘Well, not very many people are dying.’
“As a public-health person, I don’t want to see us get to that last stage.”
Maryn McKenna is a National Geographic contributor, and the author of Superbug and Beating Back the Devil. She last wrote for FERN about how the Netherlands cut antibiotic use on farms. Her new book on antibiotics in agriculture will be published by National Geographic Books/Penguin Random House in 2017. She writes regularly about antibiotics and agriculture for Ag Insider.