New resistant gene Mcr-1 worryingly portends post-antibiotic era

November 19, 2015 6:31 AM

Gene found in China final breach of humans' last line of antibiotic defence. Last year, WHO warned (see MeFi post) about the serious global threat of bacteria resistent to all known antibiotics. Now, on November 18—in the middle of WHO's World Antibiotic Resistance Week—an article in The Lancet Infectious Disease reports that scientists in China have found bacteria resistent to colistin, the antibiotic of last resort. Resistance is caused by a gene dubbed Mcr-1 which seems to have evolved in the Chinese pork industry and can be transferred between bacteria.

"Our results reveal the emergence of the first polymyxin resistance gene that is readily passed between common bacteria such as Escherichia coli and Klesbsiella pneumoniae, suggesting that the progression from extensive drug resistance to pandrug resistance is inevitable," Liu [the lead researcher] said.

Reports from International Business Times, The Guardian, BBC, The Independent.

A joint response to the article was published by Antibiotic Action, the British Society for Antimicrobial Chemotherapy, and the Journal of Antimicrobial Chemotherapy.

Two years ago, professor Otto Cars of the ReAct group, an group centered on the antibiotic resistance question and based in Uppsala University, made this video (8.5 min) explaining the "global crisis of antibiotic resistance."

"Antibiotic Action seeks to inform and educate all about the need for discovery, research and development of new treatments for bacterial infections."

"Antibiotics abuse makes China's pork industry a hotbed for drug-resistant bugs," China Economic Review, April 2015.

posted by mbrock (37 comments total)

Scary but possibly not full on apocalyptic conspiracy theory scary. I was feeling quite neurotic about antibiotic resistant issues but some reading gives some indication that there are medical directions that are too expensive now but viable directions if really needed. Not very accurate or detailed comment here but it's not as if there are no possible options.

Moving to a bio-isolated fortress in the far north is also an option.
posted by sammyo at 6:39 AM on November 19, 2015

way to go, ag industry! i knew you could do it if you really put your mind to it!
posted by indubitable at 6:49 AM on November 19, 2015 [26 favorites]

Whenever I read news related to anything that has to do with antibiotics, disease, pathogens, etc. I think of the ending of Contagion.

Nightmarish.
posted by Fizz at 6:52 AM on November 19, 2015

Welp, time to turn it in folks. Maybe the next intelligent species will do better. They'll have to, as they won't have as many fossil fuels.
posted by Hactar at 6:59 AM on November 19, 2015 [5 favorites]

This is bad, but it's worth remembering that if we truly enter the post-antibiotic age, that puts us at about the same position as the pre-antibiotic age, i.e. any time in human history before the 1930's. Humanity was surviving, most of the time people were fine. We also know much more than we used to about sterility, which can help reduce the spread of bacteria very much. It's also possible that if a strict, global moratorium is put on certain antibiotics, that bacteria might lose their resistance over time. These resistance genes have a metabolic cost to bacteria, and they'll only retain them while they're useful. Another option may be for responsible countries (I'm looking at you China) in some kind of antibiotic-responsibility consortium to invent antibiotics and keep them in reserve for extreme human use only, to prevent this type of thing from happening in livestock use.

The superbugs to worry about in a "wipes out humanity in a few months," Contagion style, are going to be viruses, if at all. They can spread much faster and be more resistant to things you can use to prevent bacterial spread, like wiping down surfaces.
posted by permiechickie at 7:00 AM on November 19, 2015 [10 favorites]

There are definitely options that exist. But this is a great condemnation of capitalistic processes guiding drug development and usage.
posted by glaucon at 7:00 AM on November 19, 2015 [7 favorites]

Humanity as a whole may survive...but this can cause a lot of suffering and death. It's not hunky-dory news.
posted by agregoli at 7:13 AM on November 19, 2015 [1 favorite]

Well wait a minute. The Lancet article isn't reporting OMG!! that the last line of antibiotic defense has been breeched. There are plenty of gram-negative bacteria already identified which are inherently colistin resistant. The Wikipedia page provides a list:

"Exceptional (inherently colistin resistant) Gram-negative bacteria

Brucella
Burkholderia cepacia
Chryseobacterium indologenes
Edwardsiella
Elizabethkingia meningoseptica
Francisella tularensis spp.
Gram-negative cocci
Helicobacter pylori
Moraxella catarrhalis
Morganella spp.
Neisseria gonorrheae and Neisseria meningitidis
Proteus
Providencia
Sebratia

What the Lancet seems to be reporting is the observation of a new vector for resistance: horizontal gene transfer.

"Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer."
posted by three blind mice at 7:23 AM on November 19, 2015 [9 favorites]

brb shutting myself off from the rest of the world
posted by Kitteh at 7:26 AM on November 19, 2015

Another option may be for responsible countries (I'm looking at you China) in some kind of antibiotic-responsibility consortium to invent antibiotics and keep them in reserve for extreme human use only, to prevent this type of thing from happening in livestock use.

China can't even manage to stop its entrepreneurs from putting poison in baby formula.
posted by No-sword at 7:29 AM on November 19, 2015 [9 favorites]

The meat industries in the US - chicken and beef, probably pork - are also abusers of antibiotics. I'm starting to see more media attention to this, but not nearly enough.
posted by theora55 at 7:29 AM on November 19, 2015 [5 favorites]

It's worth remembering that most bacterial infections are and will remain susceptible to antibiotics. You wouldn't know it from the BBC article, which uses the word "apocalypse" at least three times. But "panresistance" fortunately does not mean "pandemic." Consider: most people don't currently get really nasty infections that are resistant to everything except the colistin; you haven't become *more* likely to get that infection now.

Of the links above, Antibiotic Action seems to have a measured take on it.
posted by mark k at 7:30 AM on November 19, 2015 [2 favorites]

Come on, phage therapy funding...
posted by clockzero at 7:35 AM on November 19, 2015 [3 favorites]

This is bad, but it's worth remembering that if we truly enter the post-antibiotic age, that puts us at about the same position as the pre-antibiotic age, i.e. any time in human history before the 1930's. Humanity was surviving, most of the time people were fine.

In 1930 there were less than 30% of the current population of Earth and they were far more rural. Sure they were much much poorer and malnourished, but they were much more static and unlikely to travel, they lived under more authoritarian regimes that were able to organize effective quarantines and prevent scaremongering, children as well as the sick and the elderly were not nearly so huddled together into masses of vulnerable vectors, everyone had spent their entire lives educating their immune systems with battles against terrifying bugs.

While we do still have much more to worry about from viral diseases slipping past vaccination efforts causing pandemic disease, that not the only concern. The real worry is the slow banal tragedy of bug like Multi-drug Resistant Staphylococcus aureus (MRSA), which already kills more Americans than AIDS, returning to or exceeding their pre-antibiotic harvest of one in every twenty people who died as they re-fill the environmental niche that antibiotics have booted them from for the last 80 years. Not only will bacterial infections get much more common, they will also get much worse. Before the 1930s, we lived with S. aureus strains on our skin that existed in a complex mixture of mutualistic and virulent strategies, but antibiotics suddenly applied very strong selective pressure against any vaguely virulent strategy. Anyone with a nasty bug could just pop a pill and reset their skin. Thus, following the model, the observed sudden decrease in both virulence and transmissibility of virulent strains makes a lot of sense. However, the sudden increase in both virulence and transmissibility of virulent strains that we’ve seen in multi-drug resistant Staphylococcus aureus (MRSA) strains also makes sense. Indeed, if you look back far enough in the literature all of the crazy "new" and terrible virulence factors we are now seeing in MRSA strains all existed before the 1930s. For example, while the pyomyositis and necrotizing pneumonia we are now seeing is commonly associated with poverty, tropical climates and HIV, ie: things which didn’t get much attention prior to 1935, it was described. (At lest with this source you’ll need to wade your way past the kinds of phrases that start with “Africans are not different from any other humans, however, …” to page 1214) Until recently it would not be terribly remarkable, being easily addressed with a simple round of I.V. antibiotics. I recently found a reference in my Robbins Basic Pathology (8th ed.) which confirms that Staphylococcus aureus, as well as Klebsiella pneumoniae and Streptococcus pyogenes, has been implicated in causing necrotizing pneumonia since the turn of the century. Additionally, the PVL toxin which that first paper describes as now being found in pneumonia was initially discovered by Van deVelde in 1894 and was named after Sir Philip Noel Panton and Francis Valentine when they associated it with soft tissue infections in 1932. All of this makes logical sense anyhow, the mechanisms of antibiotic resistance are not associated with pathogenesis, even while the presence of it absolutely is.

What a return to the 1930s really means isn't just a massive amount of banally routine death, but also the end of hospitals and surgeries as we know them, the routine necessity of disruptive quarantines we no longer have the infrastructure or political will to execute, and the end of nursing homes as anything other than terrifying death camps.
posted by Blasdelb at 7:35 AM on November 19, 2015 [38 favorites]

I wonder what effect a true post-antibiotic age would have on urban planning, development, and population density trends worldwide. Would we see a move away from packing baffling numbers people into discrete spaces? A rebalancing of rural/urban populations?
posted by echocollate at 7:36 AM on November 19, 2015

Yes, there are many irresponsible actors. That's why I'm saying that it might eventually be worth it for countries to fund their own antibiotic discovery programs and to not make the chemical formulas public knowledge or to allow open sale of the new antibiotics. People will still try to steal them or make their own, but it would just be an extra hurdle to putting potentially life saving therapeutics into pigs.

I honestly think also that the public sector needs to fund antibiotic discovery anyway, since big pharma has no interest or incentive to do so. If we're already going to do this kind of thing with taxpayer money, might as well go one extra step and put a lot of pre-conditions for use on it. We could even have doctors without borders type groups that can operate in hospitals around the globe that may not be part of the consortium to give the new therapies to patients in need, still without allowing open sale.
posted by permiechickie at 7:38 AM on November 19, 2015

Come on, phage therapy funding...

Write to your Congresscritter/MEP and let them know how important phage therapy and alternatives to antibiotics generally are to you, seriously. Political pressure matters.
posted by Blasdelb at 7:40 AM on November 19, 2015 [5 favorites]

It blows my mind sometimes how many of the world's problems veganism would solve.
posted by Shepherd at 7:53 AM on November 19, 2015 [8 favorites]

I was shocked to read that colistin, apparently one of our antibiotics of last resort, is used on the scale of thousands of tonnes per year in Chinese agriculture. That seems pretty unwise.
posted by ssg at 7:56 AM on November 19, 2015 [5 favorites]

Write to your Congresscritter/MEP and let them know how important phage therapy and alternatives to antibiotics generally are to you, seriously. Political pressure matters.

Done!

Contact info for New York's Senators:

Gillibrand, Kirsten E. - (D - NY) Class I
478 Russell Senate Office Building Washington DC 20510
[phone]
Contact: www.gillibrand.senate.gov/contact/

Schumer, Charles E. - (D - NY) Class III
322 Hart Senate Office Building Washington DC 20510
[phone]
Contact: www.schumer.senate.gov/contact/email-chuck
posted by clockzero at 7:58 AM on November 19, 2015 [1 favorite]

Probiotcs, clean growing situations, good piggy food.

I knew a woman with a pig farm. She fed her pigs hospital food scraps. Yeah. So you have to figure what goes in will come out eventually. The scavenger gut leaves only worthy predators.
posted by Oyéah at 7:59 AM on November 19, 2015 [1 favorite]

"The meat industries in the US - chicken and beef, probably pork - are also abusers of antibiotics. I'm starting to see more media attention to this, but not nearly enough."

I have yet to see anything written by the press for the general public that even attempts to honestly tackle the genuinely complex question of which antimicrobials should be banned from which agricultural uses and in which contexts. We genuinely need an informed public eye acting as a watchdog to keep the agricultural industry honest and healthy but, like with so many other complex regulatory issues, eyes that compulsively see danger everywhere are no longer actually watching. There are good reasons for this to be a complicated discussion about a variety of specific antibiotics for a variety of specific agricultural applications rather than just a simple blanket prohibition.

The risks that the use of antibiotics in meat producing animals poses are very dependent on the antibiotic being used, where drugs with wider mechanisms of action that don't generate resistance or drugs with no safe application in humans have no business being banned. There is also the easily nebulous but important distinction between therapeutic and 'prophylactic' uses, where it makes no sense to keep large animal vets from treating a prize racehorse or a rural family's one cow for disease but the large operations that are the plausible problem can always ensure that their animals get sick in order to fatten them up with antibiotics. The lines that need to be drawn between what is ok and what isn't are going to necessarily be difficult to distinguish, and activists disregarding the public good to push an overly simplistic but marketable agenda hurt the needed conversation at least as much as agricultural concerns disregarding the public good to push their own bottom line.
posted by Blasdelb at 8:35 AM on November 19, 2015 [7 favorites]

Is that pig laughing at us? Bastard.


there is a critical need to re-evaluate the use of polymyxins in animals and for very close international monitoring and surveillance of MCR-1 in human and veterinary medicine.

What, so, not do the same thing we've been doing over and over until the entire system collapses and we depopulate with widespread famine, strife and chaos? Pfft.
posted by Smedleyman at 8:57 AM on November 19, 2015 [1 favorite]

One side leverages immense wealth and influence to get ag-gag laws passed and generally attempt to smother any "conversation" before it begins. The other side fails to explicitly outline exceptions for taking Fido to the vet when protesting practices that cause serious harm to humans and the environment. It's a real "both sides do it" situation, all right.
posted by No-sword at 9:01 AM on November 19, 2015

srsly though if we make it through this mess the schoolchildren of 200 years from now are going to be scandalized about how in the early 21st century even the good guys ate meat.
posted by You Can't Tip a Buick at 9:24 AM on November 19, 2015

As a pharmacologist who teaches antimicrobial resistance, my head wants to explode at the leap between a resistance plasmid being found to Colistin (which, as a drug is not available in the US because it is not THAT important) to the last antibiotic of resort has been breached.

Colistin is not the best antibiotic, not the most powerful and resistance has appeared to it before, although as mentioned, chromosomal rather than plasmid resistance. This is not good news, but even within the sphere of antimicrobial resistance it is not the worst thing going on. (I might place it as 20th worst?)
posted by dances_with_sneetches at 9:30 AM on November 19, 2015 [6 favorites]

(Seriously, Blasdelb, I understand your point, appreciate your contribution, and agree that some nuance would be good, but I think you go way too far with that "at least as much". I apologize for coming out with a sarcastic response rather than a good-faith one, though.)
posted by No-sword at 9:30 AM on November 19, 2015

I'm almost disappointed that "professor Otto Cars" doesn't work in the automotive industry
posted by Hoopo at 9:46 AM on November 19, 2015 [2 favorites]

You Can't Tip a Buick: " if we make it through this mess the schoolchildren of 200 years from now are going to be scandalized about how in the early 21st century even the good guys ate meat."

I doubt hunter gatherers are going to be scandalized by an omnivorous diet.
posted by Mitheral at 10:11 AM on November 19, 2015 [3 favorites]

Finally, living like a dirty slob pays off! Take that, housecleaning suckers.
posted by marienbad at 10:15 AM on November 19, 2015 [1 favorite]

Time to consider the quarian option.
posted by Halloween Jack at 11:00 AM on November 19, 2015

that's a different thread
posted by one weird trick at 11:52 AM on November 19, 2015 [2 favorites]

What will actually happen is we'll get a little less crazy about drug testing and get something out that works fairly quickly.

We have an Ebola vaccine now, for instance.
posted by effugas at 1:39 AM on November 21, 2015

Welp, time to turn it in folks. Maybe the next intelligent species will do better. They'll have to, as they won't have as many fossil fuels.

Well, there'll be us.
posted by carping demon at 9:17 PM on November 22, 2015

Richard James: I believed we would face an antibiotics apocalypse - until now - "Until last month I was still pessimistic about our chances of avoiding the antibiotics nightmare. But that changed when I attended a workshop in Beijing on a new approach to antibiotic development based on bacteriocins – protein antibiotics produced by bacteria to kill closely related species, and exquisitely narrow-spectrum."*
posted by kliuless at 10:04 AM on November 24, 2015

This dude mentioned the problem of immunogenicity for his peptide therapeutic, but is failing to mention all of the other problems with peptide therapeutics that have prevented almost all of the other peptide therapeutic magic bullets from working in meaningful ways. Do they require specific concentrations of any ions to work that aren't found in human tissues? How did the pharmacodynamics turn out beyond the obvious questions of immunogenicity? When he says specific, how specific exactly does he mean? Are they still seeing the super fast development of resistance through things like simple changes to membrane fluidity in these recombinant bacteriocins that people have observed over the last hundred years? How many bacteriocins exactly were found to not be immunogenic? Besides, isn't 'I suddenly believe in my work' a kind of strange angle to take in a popular press article?
posted by Blasdelb at 10:23 AM on November 24, 2015

Blasdelb,

I think it's more "Someone isn't afraid to do this" than "this works". The friction in creating new medications is vast, in the west, but the moment large numbers of people start dying the cost of inaction exceeds the cost of action. What's exciting is, even before then, we're seeing active development. Maybe not too late, even.
posted by effugas at 3:41 PM on November 24, 2015