Antibiotic resistance threat demands curb on use in animals, Canadian doctors say

Superbug bacteria in Canadian samples dating back five years that were discovered during recent tests serve as a wake-up call to stop adding antibiotics to animal feed and to boost surveillance, doctors and microbiologists say.

Surveillance recently began at hospitals across Canada and at the National Microbiology Laboratory following last November's report of resistance to an antibiotic of last resort in China.

In the journal Lancet Infectious Diseases, researchers reported finding resistant bacteria in pigs, meat and a small number of hospital patients in China. Since then, scientists in England and Wales, Denmark, Thailand and Laos, among others, have published similar findings.

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The antibiotic, colistin, was approved in the late 1950s but rarely used because its side-effects are so toxic. For instance, colistin in inhaled form is reserved for patients with chronic lung infections to avoid its toxicity elsewhere in the body.

A patient with an intra-abdominal infection at the Ottawa Hospital was a carrier for bacteria with resistance to colistin, but it's unlikely they're the cause of the infection, said Marc Desjardins, a clinical microbiologist at the hospital's diagnostic lab.

One has to assume without some very concerted efforts, during my career I'll start seeing patients that I cannot treat at all.- Dr. Michael Gardam, Toronto University Health Network

"Testing we had done had indicated that colistin probably wouldn't work with this organism," Desjardins said. "We just basically found it on the individual."

The infection was treated successfully and the woman made a full recovery.

Now, Dr. Michael Mulvey, head of antimicrobial resistance at the National Microbiology Laboratory in Winnipeg and his team's detective work has searched out the resistance mechanism, on a gene called MCR-1 found in bacteria.

Using electronic genome sequencing technology, they found the MCR-1 gene in three cases among 1,600 reviewed initially. One was from the Ottawa patient and two were in E. coli samples from ground beef sold in Ontario in December 2009 and January 2010  —  a year before the original example in China.

It's the first such finding of the gene in North or South America, which confirms its global dissemination, Mulvey said.

"We're continually looking for this MCR-1 gene to see how prevalent it is," Mulvey said Wednesday. "We're also going back prior to 2010 to see when this really showed up in Canada to get a better understanding of how long it's been around, and just trying to get a better handle on how widespread it is."

Antibiotics in livestock feed

The latest concern in the field of antibiotic resistance is bacteria can easily swap resistance genes like MCR-1 that are found on plasmids, circular pieces of DNA.

For Desjardins, one major culprit driving such antibiotic resistance is the use of livestock antibiotics in animal feed.

"When you use antibiotics in agriculture in feed to promote growth and improve economic returns, the problem is that you also put selective pressure on these organisms to develop resistance and these organisms get introduced into the food chain," he said. "They go from the animals to the humans. When they start getting introduced to humans you start to getting into problems."

The majority of these antibiotics are used in animals, said Dr. Andrew Morris, director of antimicrobial stewardship at Mount Sinai Hospital in Toronto.

"That separation between animals and humans or lack thereof is a real problem when antibiotics are used so widely," Morris said.

Suppliers have pledged not to use antibiotics in feed, but use of the drugs in agriculture hasn't been abandoned as it should be, Morris contends. Compared with countries such as Spain that have already clamped down on antibiotic use, Canada hasn't taken the problem as seriously, Morris said.

When resistance turns up in both the food supply and in humans, that's a smoking gun for microbiology sleuths who aim to stay a step ahead of the resistant bugs, said Morris, also director of the Association of Medical Microbiology and Infectious Diseases Canada.

Bacteria develop resistance if they're constantly bathed in antibiotics, said Dr. Michael Gardam, director of infection prevention and control at Toronto's University Health Network.

What's more, reserving antibiotics for patients does pay off. At Toronto hospitals, Gardam said, they've seen how making a concerted effort to control use of the drugs slashed resistance rates among pseudomonas bacteria. They've achieved similar success as a U.S. teaching hospital, with resistance dropping from 90 per cent to about 50 per cent. 

Apocalyptic scenario 

Gardam said that when he started his infectious disease training, it was unusual to see bacteria resistant to more than one antibiotic.

"Infectious diseases have gone from having a real plethora of options to having extremely limited options for many patients. One has to assume without some very concerted efforts, during my career I'll start seeing patients that I cannot treat at all."

The apocalyptic scenario could occur if bacteria become resistant to all classes of antibiotics by swapping resistance genes widely.

Gardam likens resistance to the tip of iceberg, where the tip grows every year, limiting the antibiotic options for infections in patients needing surgery such as hip replacements, people with infections during chemotherapy or those receiving organ transplants.

Morris hopes a more sophisticated and co-ordinated national surveillance for drug-resistant microbes in hospitals, long-term-care homes and in the community could help.

Current infection prevention and control steps worked in the Ottawa patient's case, Desjardins stressed. The woman was isolated to avoid putting others at risk. Such measures work not only for this latest type of antibiotic resistance but others, too.

"This is like you're on a long trek and this is just like another vista that we're getting to see there's a real problem," said Morris. "Eventually, we are going to get to the point where we have no solution.… This is not the end of the world as we see it but we are getting there. We are on our way unless we do something pretty significantly."