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Medicine Biotech

A Post-Antibiotic Future Is Looming (www.cbc.ca) 137

New submitter radaos writes: A gene enabling resistance to polymyxins, the antibiotics of last resort, has been found to be widespread in pigs and already present in some hospital patients. The research, from South China Agricultural University, has been published in The Lancet. According to research Jian-Hua Liu, "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." Work on alternatives is progressing — Dr. Richard James, former director of the University of Nottingham's center for healthcare associated infections, writes, "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."
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A Post-Antibiotic Future Is Looming

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  • by drinkypoo ( 153816 ) <martin.espinoza@gmail.com> on Sunday November 22, 2015 @08:50AM (#50979705) Homepage Journal

    when I attended a workshop in Beijing on a new approach to antibiotic development based on bacteriocins â" protein antibiotics produced by bacteria to kill closely related species, and exquisitely narrow-spectrum."

    While we've been working on making the better antibiotic, Russia has been working on phage therapy [wikipedia.org]. Of course, we are the ones with the resources to develop it, not them. It should arguably be the other way around. The problem with this idea though, which is also the same reason we have antibiotic resistance today, is that you have to identify the problem before you can use it. We have an inadequate number of medical personnel pretty much everywhere in the world, and they already can't keep up with illness even using broad-spectrum antibiotics that historically have enabled them to help people without identifying a specific pathogen. They certainly don't have the time or training to do any better. We need more medical personnel, or nothing we do to try to fight these resistant illnesses is going to make a difference because we won't have the manpower to implement it.

    • Of course, we are the ones with the resources to develop it, not them.

      Were that it so - "we" strongly disincentivize new drug development by throwing $1B roadblocks in the way of new ones. Sure, it's to help the profits of the few big pharma corps that can fund it, but the real losers are real - people who track these things have the current FDA cost at net-balance 20 million avoidable deaths (and people say the Aztecs were barbaric). As always, attempts to impose control create chaos.

      They certainly don'

    • We keep hearing about phage therapy being a possible replacement for antibiotics, but then the news never reappears as actual pharma development. Any idea why?

      • We keep hearing about phage therapy being a possible replacement for antibiotics, but then the news never reappears as actual pharma development. Any idea why?

        In my opinion there are two main problems, both covered in sibling comments. Both of them have been covered by sibling comments to yours, so I'll link to them as I go. There is a technical problem, and as usual, a political problem.

        The relative difficulty of the approach [slashdot.org] is the technical problem. Modern medical care often seems to best be represented by a shotgun. You fire a big cloud and hope you hit something. Problem is, even in the best case a broad-spectrum antibiotic punches your gut right in the...

        • The 510K equivalency approval process insures that the only drugs, therapy, or devices that are affordable to bring to market are things that are already in the system. This is convenient for the Big Drug/Device companies that own the patent portfolios for said technologies.

          The Clinical Trials process is chock full of middlemen and bureaucrats wringing megabucks out of it. I remember when a new wave of 'Regulatory Affairs' turds descended on the company I worked for. Up until then we were basically a sku

          • What that means is that phage development will not come from the US. Since the Chinese created the unstoppable superbug problem by feeding the last-resource antibiotics to pigs, perhaps they will be the ones to push phage development in out absence.

      • by ColdWetDog ( 752185 ) on Sunday November 22, 2015 @11:59AM (#50980321) Homepage

        We keep hearing about phage therapy being a possible replacement for antibiotics, but then the news never reappears as actual pharma development. Any idea why?

        Because it doesn't really work. The idea is great in the test tube - a specific virus against a specific bacteria. But two problems pop up - we often don't know what the specific bacteria is for a couple of days (until it's grown in culture) or at all in many cases. Then, if you do have a good idea, you have to get this large (megadaltan) thingy into the innermost recesses of the body without said body saying "oh no you don't" and mounting an nice immune response (which can make the original infection worse, see 'cytokine storm').

        Maybe, one of these days, researchers will manage to overcome these obstacles, but it has been a long slog with nothing to show for it so far.

    • Phage therapy's main advantage is its problem. It can't be mass-produced by the pharmaceutical industry for sale to doctors with the diagnostic ability of a search engine. You have to target the pathogen and not just group it with the likely suspects and hope that it's susceptible to the broad-spectrum antibiotic.
      • So you won't have cheap antibiotics (due to the agricultural sector wanting that extra % in profits), and the replacement will be expensive and not subject to generic production. I see nothing that big pharma would object to here.
    • by goombah99 ( 560566 ) on Sunday November 22, 2015 @10:08AM (#50979947)

      Replacing antibiotics with proteins and possibly phage is a doomed proposition if done as a simple substitution. The advantage that antibiotics have that proteins can never match is they are low molecular weight chemicals. thus you don't have to give someone a high mass dose, it can be absorbed in the gut or membranes, and it can get into cells. Furthermore proteins are relatively easy to decompose without inventing any custom hardware, they are also easy to recognize specifically (which is also why they can provoke an immune response if not properly humanized). Thus proteins are not substitutes and start out with many many orders of magnitude handicap in molecular weight and accessibility. Therefore to overcome that one needs to exploit protein therapies in different ways. proteins are good at things like catalysis. The intital activity of a chemical is stochiometric in which one chemical binds one receptor. But an enzyme can turn over many many reactions, so one can, if used right, have a manyfold activity. (on the otherhand, this advanage is not clear cut, since the receptors bound by standard chemicals may amplify the signal as well, and many desired targets medical for proteins will be stochiometric binders not catalytic enzymes). A big big advantage of proteins is their potential for specificity which will both diminish their side effects and could concentrate them into a specific target area. Imagine for instance protein therapeutic which only affected a certain pathogen and left the other bacteria in your gut alone. Finally, if the protein is large enough then it can remain in the circulatory system longer before the body removes it. But that also means higher molecular weight which can be bad.

      Phage are even higher molecular weight. But they can reproduce. And presumably they might be tailored to only infect the bad bacteria as their host for reproduction. But they also might become antigens and your own body would clear them.

      Both of these therapies have killer applications and are not to be dismissed. Their extreme specificty will completely change medicine even more than antibiotics did. But they are not in the near future any sort of replacement for antibiotics.

      • You know, there are still naturally occurring chemicals out there that exhibit broad spectrum antibiotic capabilities, that are not 'cillins, 'mycins, or 'oxins. Many of these are low molecular weight oliphins that show very strong inhibition on a wide assortment of disease organisms.

        Take for instance, lemongrass oil. Stuff kills the shit out of MRSA on culture plates-- handily beats vancomycin in efficacy in the microgram quantities.

        Better understanding of this and other oliphins, and how they cause such p

        • Just a few citations to back the prior post.

          www.sciencedirect.com/science/article/pii/S1995764510601290
          jac.oxfordjournals.org/content/47/5/565.short

          www.sciencedirect.com/science/article/pii/0378874184900576

          onlinelibrary.wiley.com/enhanced/doi/10.1046/j.1365-2672.1999.00780.x/

          The stuff actually does work.

    • Phage therapy is essentially the use of viruses against bacteria. This seems like a wonderful idea and quite specific against specific bacteria.

      For antibiotics we often want something broad-spectrum, because it takes time and a lab test to determine what germ is causing the problem. Precious time and uncertain results from the lab test.

      So right off the bat phage therapy is less useful.

      I wonder right also if the human host would mount an immune response to the phages used, effectively defending the very bacteria that the phages were intended to attack. It's a foreign antigen, after all, even a virus, why WOULDN'T your immune system attack it?

      So might it be the case that phage therapy would only work once on a given person, for a particular phage?

      So I'm not sure phage therapy really would be an effective replacement for the antibiotics we used to have. Helpful, certainly, but of limited use, maybe?

      --PeterM

    • "While we've been working on making the better antibiotic..."

      Except you haven't, many good candidate molecules get shelved for no other reason than they would complete with existing products and would cost a lot of money to get to market. It is when the shelves become empty of likely candidates to replace drugs in use that you have a problem.

      It seems as if the entire idea of antibiotics is broken, but it isn't, it is just that it is an arms race where the enemy can be tricked into forgetting how to de
    • The problem with this idea though, which is also the same reason we have antibiotic resistance today, is that you have to identify the problem before you can use it.

      Well, that is of course one of the many practical problems, but the real, undelying problem is that we, idiotically, allow short-sighted, economic interests take priority over anything else. We have known for decades that overuse of antibiotics will, by necessity, produce bacteria that are resistant. We have also discovered that bacteria exchange useful genes, seemingly across species barriers, much like we use social media. In spite of this, we have allowed, not only over-prescription of antibiotics to hum

  • Questions... (Score:5, Informative)

    by Feral Nerd ( 3929873 ) on Sunday November 22, 2015 @09:00AM (#50979739)

    A gene enabling resistance to polymyxins, the antibiotics of last resort, has been found to be widespread in pigs and already present in some hospital patients.

    Is that a roundabout way of saying that some complete and utter moron has been feeding the antibiotic of last resort to pigs in order to boost his profit margins and the resulting resistant bacteria are now spreading to humans? I could be wrong about that of course since I am not a bacteriologist, so for what other reason would polymyxins resistance be widespread in Chinese pigs and now spreading to humans?

    • Likely as not, the myopic minority in a particular sector are to be humanity's undoing.

      I mean, bacon is tasty, no doubt... but in the grand scheme of things, plausibly not worth watching a loved one perish via a slow death from antibiotic-resistant pathogens that we could neutralize a few short years ago.

      It is ever difficult to impress people barely making a living in the present with tales of doomsday futures.

      • by HiThere ( 15173 )

        It is ever difficult to impress people barely making a living in the present with tales of doomsday futures.

        While true, it *is* understandable. The problem is it's equally difficult to impress those currently getting extremely wealthy. And they're the ones with the power to change things.

        • Sure. I'm betting the profit margins for the Chinese pig farmer are pretty slim. Adding a few extra pounds per animal, or keeping an extra few animals alive per season, make a huge difference in his family's quality of life.

          Individually choosing to forego the antibiotic advantage may not even be an option for one farmer, who's tiny personal sacrifice would be essentially insignificant, and likely place him at a disadvantage to his nearest competitors.

          No, this is something the people who make the rules need

    • Re:Questions... (Score:5, Insightful)

      by Psychotria ( 953670 ) on Sunday November 22, 2015 @09:23AM (#50979797)

      Is that a roundabout way of saying that some complete and utter moron has been feeding the antibiotic of last resort to pigs in order to boost his profit margins and the resulting resistant bacteria are now spreading to humans? I could be wrong about that of course since I am not a bacteriologist, so for what other reason would polymyxins resistance be widespread in Chinese pigs and now spreading to humans?

      Essentially, yes.

      China is one of the world's largest users and producers of colistin for agriculture and veterinary use.

      (Source: TFA)

    • Re:Questions... (Score:5, Insightful)

      by dgatwood ( 11270 ) on Sunday November 22, 2015 @09:24AM (#50979801) Homepage Journal
      It's the tragedy of the commons. You have a group of sociopathic businesspeople who consider their profits more important than the survival of the human race, so they give prophylactic antibiotics to animals that aren't even sick. The downfall of humanity will be greed.
      • It's why, when a sociopath is discovered, they should immediately be removed from society permanently. Take Valeant Pharmaceuticals. The evil monsters that ran the company decided that profits far outweighed mitigating human misery, and it was only when shamed shareholders began to respond negatively that the sociopaths were forced to back down. Such monsters should be removed from society, or at the very least banned from any position where they have even the smallest amount of influence or authority over

        • Such monsters should be removed from society, or at the very least banned from any position where they have even the smallest amount of influence or authority over others. Perhaps we can re-employ them cleaning sewers.

          That's a job that's going to be done by robots soon anyway. If we instead seized the profits from monsters like these and used it to help fund a COLA then there would be nothing inhumane in the least about telling them that they are not permitted to own or operate a business of any sort in the future. They can work for someone else or they can sit around in their mud hut or concrete apartment (what do you propose they get for free, anyway?) with their thumb in their arse thinking about how much better they

        • by dryeo ( 100693 )

          There are occupations where having a sociopath is an advantage. For example surgeons, where a lack of empathy can be an advantage when cutting into people.

          • by HiThere ( 15173 )

            It takes more than a lack of empathy to make a sociopath. And a surgeon who operates unnecessarily is not a benefit to society.

            • by dryeo ( 100693 )

              It takes more than a lack of empathy to make a sociopath.

              Yes, there's also aggression and violence, or at least the genetic alleles for them. They can show up as a murderer or just an asshole.

              And a surgeon who operates unnecessarily is not a benefit to society.

              Yes, but on the other hand a surgeon who can distance themselves from the fact that they're millimeters away from killing someone and concentrate on doing the job right ca be an advantage.
              The case I was thinking of was actually a neuroscientist who is a pro-social psychopath, lots of murderers in his family including Lizzie Borden. See eg http://www.smithsonianmag.com/... [smithsonianmag.com] fo

      • It's not greed, just survival. For some unknown reason antibiotics have a synergistic growth effect on animals that are not sick so antibiotics are feed to healthy animals. In the real world most businesses are barely profitable so any action that can increase profits is used to avoid bankruptcy.

        With population pressures and increasing antibiotic resistant bacteria our whole food producing system may have to be overhauled. This aside from the massive carbon dioxide emissions from modern agriculture that mus

        • by dgatwood ( 11270 )

          It's not greed, just survival. For some unknown reason antibiotics have a synergistic growth effect on animals that are not sick so antibiotics are feed to healthy animals. In the real world most businesses are barely profitable so any action that can increase profits is used to avoid bankruptcy.

          Horses**t. The first farmers who did this did it because of greed, trying to make a bigger profit. Later farmers might have felt that it was the only way to survive, but only because the first farmers did what the

    • Odds are good that in most industrialized countries, feeding this sort of antibiotics to pigs to maximize profits would be highly illegal. On top of that, even many industrial farmers would maintain sufficiently high standards that they wouldn't need to resort to something that extreme. It's probably one of the few things they could do in the US that would have the federal government step in and kick their ass in court.

      But the reality is that there is just nothing to stop a bunch of ignorant, short-sighted,

      • Sorry to say it, but "most industrialized countries" feed antibiotics to animals routinely.

        There are only a FEW industrialized countries which ban this, notably in Europe, notably NOT in North America (though the Republic of California just enacted a ban.)

        It's NOT just a third world practice! Routine feeding of antibiotics to animals makes them gain weight faster. Market win! Industrial farmers LOVE using antibiotics.

        Your mistake was underestimating the force of greed-induced stupid.

        --PM

    • That is exactly what is happening. The researchers were monitoring pigs in farms and discovered the resistance to polymyxin/colistin. Colistin is used in pig farms in China, so it is doubtful to be just a coincidence. The researchers found 1 in 5 pigs carried the resistant E coli strain, and 1 in 7 samples of raw meat contained it.

      I was never really scared of getting trichinosis since modern medicine can deal with that. This, on the other hand...
    • "Is that a roundabout way of saying that some complete and utter moron has been feeding the antibiotic of last resort to pigs"

      Yes, this is actually happening in China. There was a BBC mention of it recently.

    • Isn't there a simple solution to this? We just drop your patent protection when you sell it or it becomes widely available for use on farms. If that's not enough we could go after other parts of the portfolio.

      • by HiThere ( 15173 )

        Wouldn't that be forbidden by the TPP?

        • Wouldn't that be forbidden by the TPP?

          It shouldn't be if we're talking a US company selling to US consumers. Plenty of European countries have put restrictions on exporting of "lethal injection" drugs to other countries, it seems reasonable that we could similarly restrict the sell of off-label use of antibiotics by fining them or limiting their patent protection. Even though I wonder how many antibiotics are still under patent protection. Many of them should be generic by now. Doing something like fining them would actually hurt the real p

      • Then you'd immediately get "false flag" operations happening as the corporate pigs fight amongst themselves to damage each other's business interests. The drugs will still be released, but by other companies seeking to damage the genuine manufacturer for other corporate strategy reasons.
  • by Misagon ( 1135 ) on Sunday November 22, 2015 @09:16AM (#50979775)

    The reason why antibiotic-resistant strains have been forming and allowed to be a problem is that people have been misusing antibiotics.

    A small scale problem is that antibiotics have been used by human patients that would not benefit from them. Other patients have stopped or cut down on using antibiotics when they have started to feel well - but before the strain has been fully eradicated. In some countries, antibiotics have even been available over the counter without prescription.

    A large scale problem is the over-used of antibiotics in agriculture. Livestock are given antibiotics in their feed as a precaution, and this is still going on on a large scale in most Western countries.
    Antibiotics-resistant strains are widespread, even the norm in many parts of the world.
    Seriously, this has to stop! We need to treat this problem seriously. If a resistant strain of bacteria is found on a farm then that farm should be put in quarantine and the stock of animals should be destroyed, like what happened when Mad Cow Disease - but instead this is seen as normal. Diseased eggs and meat are the norm, and I am not talking about third-world countries. I am talking about Western Europe and the USA.

    • Antibiotics are not fed to animals solely as a precaution. Animals that are fed antibiotics gain more weight, faster. This works on people too. Feed people antibiotics and they gain weight.

      California, in the USA, recently banned such agricultural use of antibiotics and so have some countries in Europe.

      It really is as someone said, greed/lust for profits/need to compete with others using antibiotics is the real reason why resistance is showing up.

      -PM

    • A large scale problem is the over-used of antibiotics in agriculture. Livestock are given antibiotics in their feed as a precaution, and this is still going on on a large scale in most Western countries.

      Such use has been illegal in Finland for a long time and as such Finland is, at least in this matter, one of the Good Guys(TM). Unfortunately, it's just a matter of time before the resistant strains spread here, too; we are not helping this problem develop and spread, but as long a single country continues to feed antibiotics to their livestock as a daily routine a resistant strain will sooner or later emerge and spread.

  • Super Bacteria... (Score:1, Informative)

    by Anonymous Coward

    This is why you want to avoid using anti-bacterial soap, sprays, and aerosols unless it's absolutely necessary.

  • by Anonymous Coward

    I'm still only 29, so I guess I have yet to need them, but I've taken anti-biotics once in my life and can't help but feel a tad angry at the misuse which could potentially cause my death one day.

    • I'm still only 29, so I guess I have yet to need them, but I've taken anti-biotics once in my life and can't help but feel a tad angry at the misuse which could potentially cause my death one day.

      Get ready for even more angst. Antibiotic misuse, increasing pollution, increasing occurrences of nano particles in the environment. Climate change. Plastics leaching hormonal analogs. The third - worlding of American medicine (assuming you live in the good ol USA). Nuclear proliferation. Kim Jun-Il. Donald Duck, er Trump.

      You're gonna be lucky if you make it 45.

  • Dead from antibiotics resistant bacterial infections. 3,000 people died in 9/11 in one particular year.

    USA spent $2T on subsequent wars.

    So it seems that $100T is "justified" in spending to combat antibiotic resistance, right? (Frankly, I'd be happy to see $20B increase.)

    And it pretty much has to be Government supported investment, the market case just isn't there for a drug company to develop new antibiotics. How do you make your billions back from a drug which people just take for a little while, while they are sick?

    Drug companies just want to develop drugs that make them lots of money, drugs that people will take every day or will take in huge quantities. So if a drug company DOES develop an antibiotic, they'll soon sell it for agricultural use to help animals gain weight--that's the only way they can ever make money.

    Free market economics pretty much dictate that antibiotics will be misused if developed at all, that is why we have to have PUBLIC investment in new antibiotics.

    -PeterM

  • Maintaining antibiotic resistance is costly, and populations of bacteria which are not exposed to antibiotics will drop the capability after a while or be out-competed by competitors without the baggage.

    So maybe a world-wide complete ban on use of some of the older antibiotics that are now mostly useless would help? Bacteria resistant to those old antibiotics might become rare due to lack of selection pressure.

    Then, after 20 years of rest, maybe those antibiotics could be rotated back into use, because they've again become useful?

    --PeterM

    • by ColdWetDog ( 752185 ) on Sunday November 22, 2015 @12:16PM (#50980419) Homepage

      Yes, sort of. But that turns out not to be a big deal (from the bacterium's point of view). Even when bacterial growth is metabolically limited, the increased metabolic cost of a couple of plasmids is quite small. Yes, mutations in the antibiotic resistant gene will essentially be silent and could be competed out, but with several hundred plasmids holding dozens of 'cassettes' of antibiotic resistance, this is a slow process.

      So, this strategy does work to an extent but not as well as you would like and as soon as the antibiotic goes back on line, the problem restarts pretty quickly.

  • Polymixin use in humans is extremely rare. Guess where this resistance is coming from? Veterinary use of prophylactic antibiotics to boost livestock yields.
  • by Anonymous Coward

    don't give last-resort medicine to farmers, keep it in highly controlled conditions only (like: only administer in hospitals)

  • For thousands of years silver was the antibiotic of choice. Unfortunately nobody can patent silver, so pharmaceutical companies opted for other methods of germ fighting.

    According to sciencemag.org "Silver ions perform their deadly work by punching holes in bacterial membranes and wreaking havoc once inside. They bind to essential cell components like DNA, preventing the bacteria from performing even their most basic functions."

    In particular a recent article reveals that dead bacteria containing silver ions

  • by Anonymous Coward

    Then you'll see some action.

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