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Last-Ditch Drug Resistance: An Early Warning And Chance to Act

An intensive pig farm from the air.
An intensive pig farm from the air.
Photograph by Maryn McKenna.

There has been a lot of news about MCR, the new resistance factor that allows bacteria to protect themselves agains the last-ditch antibiotic colistin. Quick recap of what’s known so far: Chinese and British researchers found the gene mcr-1, conferring colistin resistance, in pigs, meat, and hospital patients, and realized that the gene resided on a mobile genetic element that would allow it to move easily among bacteria. Then it was identified in Portugal and Malaysia, and researchers in Denmark discovered it had been present in their country since 2012. After that, England announced it had found MCR in both patients and meat. On Thursday, the count of countries where it has been found doubled, to 10, and researchers revealed that bacteria carrying the gene were being carried unknowingly by healthy people. And other researchers say that more reports of MCR in more countries are coming soon.

So it’s worth emphasizing something that may have been obscured in the alarm over MCR’s emergence. As far as anyone has reported, no one has yet died of the colistin resistance conferred by this gene. It was identified in bacterial samples taken from people who were hospitalized for other reasons, or who were participating in routine surveillance projects.

That no one is known to have died from this doesn’t mean it is not a serious matter. What it means, instead, is that—possibly for the first time—a major public health threat has been identified molecularly, before the point at which it began to make people ill. That not only provides a better chance of recognizing where it is moving. It might also allow us to head it off.

“This is something new,” confirms Jean Patel, PhD, who is deputy director of the Office of Antimicrobial resistance at the Centers for Disease Control and Prevention. “We didn’t have to wait for people to get sick. We found out about this resistance early.”

That happened, she said, because of the “aggressive surveillance that was occurring in China, in food-producing animals, in retail meat and in humans.” (The first finding of the gene, according to the first paper, came from a sample taken on an intensive pig farm outside Shanghai in July 2013.) In fact, she said, the Chinese routine-surveillance program that allowed the gene to be found may be more robust than the ones we have here in the United States. The NARMS program (National Antimicrobial Resistance Monitoring System), which is shared by the CDC, Food and Drug Administration, and US Department of Agriculture, samples human patients, retail meat, and animals—but the animal sampling is limited. Politicians and advocates have pressed the USDA for years to improve its surveillance by going onto farms to discover what resistant bacteria flourish on live animals, but that has proved politically touchy, and the USDA is only now exploring how that might work.

(Patel added that when the existence of MCR was disclosed last month, the FDA and USDA went back through their NARMS records, and the CDC did the same for both its NARMS data and its Emerging Infections Program. None of those searches, she said, identified any MCR in the United States.)

The ability of the CDC and the other federal health agencies to track emerging threats ought to be strengthened by the just-passed Congressional budget agreement. That deal included—just for antibiotic resistance—$100 million for the National Institutes of Health, $41 million for the FDA, and $211 million to the CDC, for three programs: its new Antibiotic Resistance Solutions Initiative; its National Healthcare Safety Network, which tracks infections in hospitals; and an advanced molecular detection project, which would increase the agency’s ability to conduct the kind of analyses that identified mcr-1 in China. Patel said one use of the new funding will be to construct a network of rapid-response labs across the country that will conduct whole genome sequencing of resistant bacteria and add the results to a shared database.

(Unfortunately, the agreement took $20 million in antibiotic-resistance money away from the 2015 budget of the USDA. The White House had asked for $77 million that would go to four USDA programs that work on aspects of resistance, but the final agreement included none.)

Recognizing MCR this far in advance, though, doesn’t only provide the opportunity to tune up molecular diagnostics. It also might permit taking action to slow the emergence and spread of MCR. But that will require political will, because there is really only one way to accomplish it: stop overusing colistin, so that bacteria no longer need to evolve defenses against it.

That will be a struggle. Where colistin is being overused is not in medicine, but in agriculture, to speed up production in economies with rising appetites for meat. And controlling antibiotic overuse in agriculture has been a hard-fought global fight for decades; for every country that reduces use of the drugs, another steps up to waste them.

It’s possible that, this time, the realization that agricultural overuse is endangering the last antibiotic might be enough to create change.

“Let’s use this realization to face what’s going on,” Lance Price, PhD, founder of the Antibiotic Resistance Action Center at George Washington University, told me. Price is one of the leading researchers worldwide doing genomic analysis that reveals the global movement of resistance genes. “Let’s call for a global ban on the use of colistin, and all the other antibiotics that are crucial to preserve.

“Let’s draw a line,” he said. “Here’s what you can have for animals, and here’s what we are going to protect because we need them. And whatever we allow to be used in animals, agriculture had better figure out how to preserve those antibiotics. Because if you ruin those, we’re not going to let you have the drugs we need.”

 

4 thoughts on “Last-Ditch Drug Resistance: An Early Warning And Chance to Act

  1. Good work, Maryn. Much in these articles to provide more food for thought.
    I wonder if you could think about seeking an extended dialogue with a legal firm to tease out the threads. I mean, in the end, the food animal industries in the US are unlikely to move unless it can be proven, in court, that their practice(s) are cause(s) of harms. Proving a “mobile genetic element” as a cause may be a challenge.
    Also, as you say “animal sampling is limited”, but it’s possible, maybe even plausible, that individual producers are doing their own surveillance on the entire chain from piggery right through to effluent from households.
    MM: Thank you! And yes, I suspect you are right…

    1. I would add that the main limiting factor for on-farm sampling is not participation by the farms – it is funding from the govt. their budget line for this is pathetic considering its importance. Supposedly our govt agencies are supposed to monitor before/after the mandatory withdrawal to see if it has an impact on resistance. But they have no money and no plan to do so. We are setting ourselves up for failure by not being prepared to adequately assess this with sound scientific design. It makes me sad.

      MM: I don’t disagree that the funding situation especially at the USDA is terrible! This round was especially disappointing. But USDA has been negotiating the on-farm issue for several years now and at the update meeting they held in August, it sounded to me as though funding wasn’t the only issue. (I think one of your U Minn colleagues has been involved in negotiating this?)

  2. I was wondering about the maintenance of these antibiotic resistance genes/plasmids. Bacteria typically don’t keep extraneous DNA around due to the increased fitness cost, unless there is selective pressure. Are the levels of these antibiotics high enough in the environment now to keep the selective pressure on these bacteria to keep the various resistance plasmids? Would it be possible to set up a cycle of medical antibiotic use (ie: stop using cephalosporins for a few years) in an attempt to get bacteria to dump a particular resistance gene, or are these resistance genes basically permanent now due to high levels of agricultural use?

    MM: It’s a good question. A problem, I think, is that AR genes don’t always impose a fitness cost; there are some that have hung out quite comfortably even after the drugs that imposed the selective pressure were withdrawn. (But I will have to look up which.) This gene is in several different plasmids so far; the studies of it are still very early!

  3. Collistin ban should be a good initiative to start deeper concers against antibiotic which is being used in human being as a last resort even though the probability of kidney failure always remains.

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