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The world is headed for a post-antibiotic era
April 30, 2014 9:21 AM   Subscribe

WHO’s first global report on antibiotic resistance reveals serious, worldwide threat to public health. "The world is headed for a post-antibiotic era, in which common infections and minor injuries which have been treatable for decades can once again kill." - Dr Keiji Fukuda, WHO’s Assistant Director-General for Health Security.

The report, Antimicrobial resistance: global report on surveillance 2014, can be found and downloaded for free here.


Key findings from the report include:
  • Resistance to the treatment of last resort for life-threatening infections caused by a common intestinal bacteria, Klebsiella pneumoniae–carbapenem antibiotics–has spread to all regions of the world. K. pneumoniae is a major cause of hospital-acquired infections such as pneumonia, bloodstream infections, infections in newborns and intensive-care unit patients. In some countries, because of resistance, carbapenem antibiotics would not work in more than half of people treated for K. pneumoniae infections.

  • Resistance to one of the most widely used antibacterial medicines for the treatment of urinary tract infections caused by E. coli–fluoroquinolones–is very widespread. In the 1980s, when these drugs were first introduced, resistance was virtually zero. Today, there are countries in many parts of the world where this treatment is now ineffective in more than half of patients.

  • Treatment failure to the last resort of treatment for gonorrhoea–third generation cephalosporins–has been confirmed in Austria, Australia, Canada, France, Japan, Norway, Slovenia, South Africa, Sweden and the United Kingdom. More than 1 million people are infected with gonorrhoea around the world every day.
  • Antibiotic resistance causes people to be sick for longer and increases the risk of death. For example, people with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection. Resistance also increases the cost of health care with lengthier stays in hospital and more intensive care required.
Handy infographic.
posted by KokuRyu (110 comments total) 45 users marked this as a favorite

 
I mean this literally: this is the medium-term threat out planet must deal with most. (Well, the humans on it, anyways.)

Or to be very market-driven: This will kill more people more quickly than global warming will, for better and for worse.
posted by andreaazure at 9:29 AM on April 30 [15 favorites]


If it wasn't for antibiotics, I might have a stump rather than a scar on my right arm. And I'd probably be missing an eye, as well.
posted by showbiz_liz at 9:34 AM on April 30 [5 favorites]


Yes, this worries me almost as much as climate change. Not to mention it's yet another way in which factory farming is utterly evil (low-dose antibiotics used in farm animals to lessen infection in stressful, unnatural environments=rise of antibiotic resistance).
posted by whistle pig at 9:34 AM on April 30 [17 favorites]


Hasn't the link between antibiotic use in farm animals and antibiotic resistance in humans been established with some certainty? The FDA seems to think so. I'm surprised this isn't explicitly stated under WHO's "how to tackle resistance". Right now, action on this front doesn't seem to be very urgent -- for instance, the FDA's response has been to encourage "voluntary participation".
posted by tybeet at 9:35 AM on April 30 [3 favorites]


every dark cloud has a silver lining. maybe this will kill enough people to save the planet from global warming. tune in tonight for the debut of my new show "ask a polar bear".
posted by bruce at 9:36 AM on April 30 [8 favorites]


There was a Quirks & Quarks segment about this recently.
posted by zeptoweasel at 9:37 AM on April 30 [1 favorite]


This does scare me. It's like sun is starting to set on the golden age of easily treated health problems.

I wonder if viruses are getting more nasty. I was sick for 6 weeks last summer due to a virus. I hadn't been that sick for that long in 20 years.
posted by St. Peepsburg at 9:44 AM on April 30


maybe this will kill enough people to save the planet from global warming.

Interesting to consider in the abstract, although I don't think I would like to see my children die, or my wife die, as a result of infection. Bad enough that my son had an eye infection last week, but to die like that. As a matter of fact, he nearly died of sepsis several days after birth. To call the experience frightening is an understatement, but I suppose you would have to have children or other loved ones to get it.

If we are going to "save our planet" we have to focus on our humanity and humane solutions, rather than Final Solutions.
posted by KokuRyu at 9:45 AM on April 30 [30 favorites]


To answer my own question, it does appear that there is a section in the full report that is explicitly devoted to the issue of antibiotic use with farm animals.
posted by tybeet at 9:46 AM on April 30 [1 favorite]


So, supposing that the best way to avoid getting killed by a nasty infection in a post-antibiotic world is to avoid getting an infection in the first place, what should I do? Wash my hands very thoroughly? Avoid hospitals?
posted by mai at 9:46 AM on April 30 [3 favorites]


But without antibiotics how would I enjoy my $1.49/lb feces-fed tilapia?
posted by RobotVoodooPower at 9:47 AM on April 30 [7 favorites]


And clean your cuts immediately.
posted by St. Peepsburg at 9:47 AM on April 30 [5 favorites]


So what did people do before antibiotics - did they die, or did it just take longer to get better (or both)?

It seems like doctors really over-prescribe antibiotics too. I often get given a prescription of antibiotics "just in case" and I only fill it when I can feel things getting worse, not better.
posted by St. Peepsburg at 9:50 AM on April 30


If we are going to "save our planet" we have to focus on our humanity and humane solutions, rather than Final Solutions.

Seriously. Anyone advocating widespread death and suffering as the solution to global warming is politely invited to be the first in line.
posted by showbiz_liz at 9:50 AM on April 30 [28 favorites]


I agree that the one percent probably can not buy their way out of this but I also would guess that the 1% will be instrumental in providing the capital to finance research and development ( and make money).

Isn't a large part of the problem that no research money is being spent on developing new strains of antibiotics, because there's not enough profit margin vs the research costs? Somehow I doubt that "the 1%" (or thier pharma companies) are going to change that calculus for the good of the world anytime soon, the investment will need to come from government dollars. And basic research spending has been drastically curtailed by 1% coddling spending cuts that are the new permanent state of political normal.

Or maybe we really are losing the race against microbial evolution, but it might be nice to have the research to know one way or the other funded.
posted by T.D. Strange at 9:51 AM on April 30 [14 favorites]


And why can't they just create new antibiotics? I'm ignorant here so biologists please chime in at any time.
posted by St. Peepsburg at 9:51 AM on April 30


So, supposing that the best way to avoid getting killed by a nasty infection in a post-antibiotic world is to avoid getting an infection in the first place, what should I do? Wash my hands very thoroughly? Avoid hospitals?

It is very difficult to avoid "germs." With our son, he developed sepsis (this is when your blood becomes infected) after developing bacterial meningitis. He nearly died, and it was not antibiotics alone that saved him - I will always be thankful to the doctors and staff at Obama municipal hospital in Fukui Prefecture, in Japan.

How did he get infected? Nobody knows.

Indeed, a work contact of mine who had a liver transplant a few years ago recently came down with sepsis. Thankfully she recovered, but once again nobody knows how she picked it up.

That said, washing your hands, and washing them well, is pretty key.
posted by KokuRyu at 9:53 AM on April 30 [2 favorites]


So what did people do before antibiotics - did they die, or did it just take longer to get better (or both)?

Many developed real expertise at dying. Others were lucky and just took longer to heal. Sometimes they were very unlucky and suffered a long time before they died, like this writer's uncle.
posted by maudlin at 9:54 AM on April 30


So what did people do before antibiotics?

They drank beer.
posted by RobotVoodooPower at 9:55 AM on April 30


Minimizing exposure through hygiene is one thing. Living a healthy life so that your immune system can fight off infections on its own, is another. WRT the latter, the usual advice applies: exercise regularly, eat lots of fruits and veggies, avoid bad stress.
posted by tybeet at 9:56 AM on April 30 [1 favorite]


And why can't they just create new antibiotics? I'm ignorant here so biologists please chime in at any time.

Pretty tough to wage a selective chemical war. You could say we got pretty freaking lucky with the bread mould.
posted by Trochanter at 9:59 AM on April 30 [5 favorites]


I'm not necessarily ragging on the 1%, but, yeah, if you are rich you can demand the most cutting-edge antibiotics which costs thousands of dollars per dosing schedule. Of course, being rich doesn't mean you necessarily get the best doctors. (I remember hearing a medical commentator years back saying the very rich and the very poor are more likely to get the worst doctors. Recent example: Michael Jackson.)

One of the major problems is that the organisms are becoming resistant to commonly used and cheap antibiotics. This affects the third world first and the rest of us second.
posted by dances_with_sneetches at 9:59 AM on April 30 [1 favorite]


"Obama municipal hospital..."

this is the first miracle he needs for his eventual canonization. can i be appointed as the advocate before the sacred congregation for the causes of saints if i'm not catholic?
posted by bruce at 10:00 AM on April 30 [1 favorite]


What I worry about isn't so much just getting an infection (although that worries me plenty); I worry about how much more dangerous surgery is going to become, and cancer treatment, and everything that lowers your resistance.
posted by Frowner at 10:00 AM on April 30 [21 favorites]


this is the first miracle he needs for his eventual canonization. can i be appointed as the advocate before the sacred congregation for the causes of saints if i'm not catholic?

Obama municipality.
posted by Frowner at 10:01 AM on April 30 [1 favorite]


So, supposing that the best way to avoid getting killed by a nasty infection in a post-antibiotic world is to avoid getting an infection in the first place, what should I do? Wash my hands very thoroughly? Avoid hospitals?

Yes to both, I guess. I live in Japan, and it is very common there, when returning home, to gargle some water and wash one's hands. Additionally, as a courtesy, many people wear surgical masks when they are ill to avoid spreading disease on subways, at work, anywhere in public really.

I don't know how effective all this is, but I suppose it can't hurt and I go along with it at my (Japanese) wife's insistence. I once read that some health authorities attribute at least some of the failure of SARS to spread in Japan to these practices. That being said, I don't know the truth of that matter, but again, it can't possibly hurt.
posted by robatsu at 10:04 AM on April 30 [1 favorite]


Minimizing exposure through hygiene is one thing. Living a healthy life so that your immune system can fight off infections on its own, is another. WRT the latter, the usual advice applies: exercise regularly, eat lots of fruits and veggies, avoid bad stress.

All the veggies in the world won't save you from gangrene.
posted by showbiz_liz at 10:04 AM on April 30 [16 favorites]


So what did people do before antibiotics - did they die, or did it just take longer to get better (or both)?
Some of both. My great-uncle died at the age of 18 of an ear infection, but that wasn't very typical. Most healthy people will be able to fight off your run-of-the-mill infections. But people with compromised immune systems often can't fight off those infections, which means that very young children, among other vulnerable groups, had much higher death rates in the pre-antibiotic era. And as other posters have pointed out, antibiotics hugely reduce the risk of death from serious injury, surgery and the like.
posted by ArbitraryAndCapricious at 10:04 AM on April 30 [1 favorite]


Minimizing exposure through hygiene is one thing. Living a healthy life so that your immune system can fight off infections on its own, is another. WRT the latter, the usual advice applies: exercise regularly, eat lots of fruits and veggies, avoid bad stress.

Also, never get a cut that breaks the skin. Especially make sure to never have surgery.
posted by justsomebodythatyouusedtoknow at 10:05 AM on April 30 [17 favorites]


Also, yeah, as Frowner just pointed out- this would end or at least severely curtail any and all chest cavity surgery. Hope you don't need a heart transplant!
posted by showbiz_liz at 10:05 AM on April 30


showbiz_liz: "All the veggies in the world won't save you from gangrene."

No, but a healthy lifestyle could save you from a life-threatening case of pneumonia.

I don't mean to suggest that a healthy lifestyle is a panacea, just that it's a good precautionary measure.
posted by tybeet at 10:07 AM on April 30


I live a healthy lifestyle. I might still be dead without antibiotics, as might half the people you know and love.
posted by showbiz_liz at 10:08 AM on April 30 [10 favorites]


Antibiotic resistance happens when a bacterium develops a workaround to the pathway that a given antibiotic interrupts. So trying to lay this at the feet of factory farming, while a great soundbite, ignores the fact that there are multiple classes of antibiotics not used in agriculture where resistance is still happening. It's too complex a problem to scapegoat any one cause.

They are developing new antibiotics, but there are only so many common pathways you can go after until you're chasing individual strains of bacteria, not whole classes.
posted by Kid Charlemagne at 10:09 AM on April 30 [10 favorites]


I think it's worth pointing out that the "population explosion" has been a result, in part, from lower infant mortality post-1945. So antibiotic resistance has the potential to impact children under the age of 7 (0-7 are the danger years with traditionally highest rates of infant mortality).
posted by KokuRyu at 10:10 AM on April 30 [5 favorites]


And why can't they just create new antibiotics? I'm ignorant here so biologists please chime in at any time.

An antibiotic is, essentially, a toxin. (This under the principle that if you're taking a pill and it has no side effects, it's called Pez.) It is tuned to be lethal to the desired bacteria and non-lethal to the person housing said bacteria.

Now, the list of compounds and natural things that function in that manner is fairly small. It grows smaller yet as resistance grows among bacterial strains. New antibiotics are difficult to create simply because all of the low-hanging fruit in that field has been plucked; there isn't a lot out there that hasn't been tried that checks both the [ ] kills the right bacteria en masse and [ ] doesn't kill the patient boxes. Some of the more protected and underused antibiotics at present are rarely used specifically _because_ they're very fiddly on the 'doesn't kill the patient' front.

Also, it's not a sexy and highly profitable front for drug companies to investigate. Pills that make your pecker hard? They're profitable. Diabetes management drugs for an increasingly portly American public? Profitable. Antibiotic research is often a lot of good money thrown after bad when results aren't reached, and many drug companies prefer to stick to surer bets.
posted by delfin at 10:12 AM on April 30 [4 favorites]


also, avoid sex with people you don't know.
posted by bruce at 10:12 AM on April 30


Look on the bright side: chicken is really cheap.
posted by justsomebodythatyouusedtoknow at 10:14 AM on April 30 [1 favorite]


chicken is really cheap because they cram 'em in there to maximum density and forestall disease with, wait for it...antibiotics! old-fashioned artisanal chicken will cost as much as today's beef.
posted by bruce at 10:18 AM on April 30


Next up, phage therapy. And when we've overused that to the point of uselessness we may have found something else. Or found that, miracle of miracles, penicillin now somehow works again on routine and previously-resistant-in-the-distant-past infections.

Though the friends I've talked to about phage therapy were a little iffy on the name.
posted by Slackermagee at 10:22 AM on April 30


I've been wondering what is the likelihood that phages can replace antibiotics before the post-antibiotic era fully materializes?
Phages are more bacteria-specific, which is incredibly targeted and useful compared to antibiotics for some uses, but for other uses (such as general prophylaxis against infection during surgery) that specificity is a problem.
"Phage therapy" is already becoming a thing, but not (yet) in any way that fills the shoes of antibiotics.
posted by anonymisc at 10:22 AM on April 30


showbiz_liz: "I live a healthy lifestyle. I might still be dead without antibiotics, as might half the people you know and love."

And I think this hits one of the roots of the problem, if only in a roundabout way. Healthy and diet are essentially systemic issues. So is production of antibiotics. Diet, of course, also has that extra issue, mentioned above, of antibiotic feed to livestock.

Since Capitalism ultimately seeks private gain as much as possible (with the hidden assumption that the benefits spread to all, aka: invisible hand), it does not deal with systemic issues. It focuses only on its own egoic, private gain. There may be individuals who attempt to push issues (a la Bill and Melinda Gates Foundation malaria work), but in the end, the issue is much larger than any single factor.

The food we eat, our handwashing/hygiene practices (in third world you can add plumbing and waste, hell, even in the first world, in poor enough locations you can add that issue). Our interactions, population density, transport modes and contact with others.

Mitigation/prevention is one part of the equation. Finding new antibiotics is another. I have a feeling that the best methods will work on targeting multiple modes of action on bacteria at once to work on preventing the spread of the diseases. But without funding, without the recognition that we are social animals and that we have a SOCIETY that needs to work together on certain issues, we ultimately will fail. Well, I shouldn't say that, we have been lucky before, maybe we'll keep getting lucky. A single magical discovery from a lone genius inventor.

In the end, though, I think one of the fundamental issues facing humanity in terms of solving the large scale problems of the future is the masses lack of understanding systems. Of being enslaved by systems (i.e. bought off by those with vested interests in keeping the status quo, while they face no harm in the short term for not dealing with these problems), or buying propaganda of these interests, if they have no real power to dictate solutions, such that they continue to put into place decision makers who continue to act against the public interest at large.

Yes, it's a political discussion, and no, I don't have any answer. Have we ever found a truly satisfactory answer? Perhaps the closest is the Scandinavian Social Democracy model.

I almost feel like some of these socially oriented societies exist precisely because they are forced to come together in very harsh conditions, and once a society gets large enough that the benefits accrue to certain factions, that the immediate dangers of the environment is lessened to a certain degree and power is wielded and maintained for those who have attained it, at the detriment of those who no longer have access to those power structures, and they being to advocate systems that benefit them, and since they have access to the systems of narrative, our dominant discourse is now perpetuated by those who have the least pressure to bear on them (despite their mental belief that they are totally at ruin if they lose a few million personally, but still have billions in the bank)...

If things do fall, I think we'll see a resurgence of an understanding that we're all in this together, but it takes a mighty damn hard fall on a Goliath before it gets to that point. And all the David's below are a bit afraid of what might happen in the meantime, so nobody dares throw a stone, lest it all come crumbling down.

Shuffle along, shuffle along until reality slaps us hard in the face and we're forced to deal with reality as she is, not reality as we want her to be.
posted by symbioid at 10:23 AM on April 30 [15 favorites]


Wow, sobering outlook. I'm not sure limiting it to "health care professionals" would do much though. We're part of the problem for many reasons -- one of which is we fear patients might go to some other person if we won't give them antibiotics (yes free market in medicine, it's great right?!?!) but also because treating over-broadly is really easy (just prescribe something more powerful, it will kill everything!) and because sometimes people want to get better faster and an antibiotic aids the placebo effect in getting you there even if your infection was not bacterial.

In the US, a serious solution would call for serious antibiotic stewardship where infectious disease docs/specialists (who are usually uniformly very conservative when it comes to prescribing antibiotics) control a lot more of the decision making as to who gets antibiotics (it won't happen).

In other places, it's going to be a lot tougher. You can get ciprofloxacin over the counter in Mexico (no wonder what used be a drug that treated 95% of urinary tract infections now treats about 50% -- that's right an essential coin flip that your drug is doing anything). I've heard where it's just about as easy to get antibiotics in other countries.

It's going to take a big global regulatory system to curtail this problem and I can't see that happening until it gets too bad or it's too late. You'd have to treat antibiotics like nuclear weapons.

Either that are pharmaceuticals or the government are going to have get serious about making "designer drugs" that work on a genetic/immunologic level (like you see with all the new "immunologic" medicines in the cancer field). People in the "integrative proteomics" field are working on it, but the cost models are just not there to justify Big Pharma getting behind that R&D. That means the government needs to do it or get the science good enough so that Pharma can industrialize it. And, sadly, it's not happening in an era of reduced NIH spending.

But wow, I'm glad they used the strong language here. It's a problem we see coming, are not stopping, and have no solution for should the projections above occcur. :(

If other people in the know have links or some inside info on where exactly the science of "proteomics" and antibiotics is, that would be great -- I heard a grand rounds on it a while ago, but the guy said it's pretty far from happening and mentioned the cost factors about it.
posted by skepticallypleased at 10:27 AM on April 30 [2 favorites]


Minimizing exposure through hygiene is one thing. Living a healthy life so that your immune system can fight off infections on its own, is another. WRT the latter, the usual advice applies: exercise regularly, eat lots of fruits and veggies.

Yeah, my step dad did all that, and even so, he died quickly of a MRSA infection a couple years back.
posted by krinklyfig at 10:27 AM on April 30 [8 favorites]


The crazy part about antibiotics use in chickens say is that the antibiotics actually promote growth as well as help keep chickens from getting sick. I was listening to something on NPR about this and they were saying that Americans have something like double the amount of courses of antibiotics as opposed to say those from the Nordic countries.
posted by Carillon at 10:32 AM on April 30


St. Peepsburg: "And why can't they just create new antibiotics? I'm ignorant here so biologists please chime in at any time."
Understanding what makes antibiotics so difficult to find requires a working understanding of what they are and what makes them so awesome.

Antibiotics are so useful because they are compounds that are more toxic to the bacteria attacking us then they are to us. For example, while bleach is really really effective at being toxic to bacteria, it would not be a good antibiotic because it is also pretty darn toxic to us. In a very rough sense, how good an antibiotic is depends on its effectiveness, as generally abstracted by its Minimum Inhibitory Concentration (MIC) or the lowest concentration of the stuff necessary to stop the growth of the bacteria in question, versus its toxicity to us measured in approximate LD50, or the concentration that is likely to kill half your patients. Antibiotics are able to be differently toxic by taking advantage of differences between bacteria and us, and there are indeed depressingly few. These days, most antibiotics work by taking advantage of the fact that bacterial ribosomes are pretty different from ours and work by acting as a monkey wrench that fucks up theirs but doesn't fit into ours. There are also some other important antibiotics that target things like differences in DNA synthesis, membrane synthesis, central metabolism, and a few others. They are a selective toxin, and unfortunately there is a depressingly short list of differences between you and the bacteria that ail you to take advantage of by selecting against.

What good antibiotics do is they give you a pill that doesn't need to be kept cold, doesn't harm patients, and address most infections in a matter of hours. Antibiotics have taken almost all of the major causes of human death and addressed them so thoroughly that we hardly even remember them - nearly erased from our culture.
posted by Blasdelb at 10:33 AM on April 30 [16 favorites]


Obama municipality.

It's a lovely, lovely town.
posted by KokuRyu at 10:34 AM on April 30 [1 favorite]


Before antibiotics were widespread around 40% of deaths were due to bacterial infection. Going back to that is not a good thing
posted by sotonohito at 10:35 AM on April 30 [2 favorites]


I sure some very wealthy person's child has died from some antibiotic-resistant strain by now. Why hasn't this problem been solved?
posted by Revvy at 10:35 AM on April 30


Because there is no single wealthy person on earth rich enough or influential enough to go up against Big Agro and its almighty lobbying power.
posted by elizardbits at 10:40 AM on April 30 [2 favorites]


Also, a significant portion of Americans would willingly go without affordable health care if it meant that undesirables didn't get it either.
posted by delfin at 10:41 AM on April 30 [10 favorites]


Because there is no single wealthy person on earth rich enough or influential enough to go up against Big Agro and its almighty lobbying power.

No. It's because that person is busy fighting Malaria.
posted by Talez at 10:42 AM on April 30 [17 favorites]


I'm glad they used the strong language here

Me too, but let's be honest: it's not going to make a difference so they really needn't have bothered. This is basically just one of those signs you'd see on old Roadrunner cartoons; the sort of "Beware! Cliff!" thing Coyote would notice just as he steps off the edge of the abyss.

Didn't do him any good, won't do us any good.
posted by aramaic at 10:44 AM on April 30


Because there is no single wealthy person on earth rich enough or influential enough to go up against Big Agro and its almighty lobbying power.

I don't get the Tea Party/OWS rhetoric here. Antibiotic resistance is a complex problem, with some aspect of "the tragedy of the commons."

The biggest enemy is not Big Ag or plutocrats, but sheer evolution. Pathogens have evolved rapidly, as they tend to do, over the past 70 years. Antibiotics weren't really developed with that fact in mind. It's a complex system.
posted by KokuRyu at 10:48 AM on April 30 [3 favorites]


antibiotics are fed to animals more because they make them really fat really quickly than to stave off disease, tho it's used for that as well. sigh.
posted by xammerboy at 10:53 AM on April 30 [1 favorite]


I don't get the Tea Party/OWS rhetoric here.

Oh my god, what a hilariously bizarre inference to make from my comment. My point is if antibiotic use in food animals is contributing to antibiotic resistant infections in humans, as it appears to be, then cutting back on antibiotic use in food animals could potentially have long-term benefits. Unfortunately that would cut into the agricultural industry's profits, which makes these changes unlikely. I'm sorry my crazy partisan rhetoric was unclear to you in this matter.
posted by elizardbits at 10:55 AM on April 30 [16 favorites]


Also, a significant portion of Americans would willingly go without affordable health care if it meant that undesirables didn't get it either.

This a billion times is the reason for most of United State's woes. Still smarting over our deciding we do not want cheaper, better healthcare.
posted by xammerboy at 10:56 AM on April 30


The biggest enemy is not Big Ag or plutocrats, but sheer evolution
Well, there's not a whole lot we can do about evolution, so if you're focused on trying to find solutions, that's probably not the thing to target.

But it is probably worth pointing out that this is not solely a US problem, and focusing exclusively on Big Ag is a little provincial. It's a big part of the problem in the US, but fixing it needs to be part of global reform in the way that people use antibiotics.
posted by ArbitraryAndCapricious at 10:57 AM on April 30


Dude, acknowledging that this is a huge threat and that viruses might indeed reduce our population enough that modern activities causing global warming are drastically reduced or stopped is not the same as wishing the deaths of your loved ones or some kind of genocidal fantasy. Sheesh.
posted by agregoli at 10:59 AM on April 30 [1 favorite]


No. It's because that person is busy fighting Malaria

Yeah, and also because maybe half of the remaining top 10 are opposed to such reforms worldwide.
posted by elizardbits at 10:59 AM on April 30


There's a lot of modern medicine that counts on being able stop infections while suppressing the bodies own immunity. Those treatments get very, very dangerous in a post antibiotic world. Have you got arthritis, asthma, psoriasis, IBS, etc? You probably shouldn't take your immunosuppresant drugs any more, because your immune system needs all the help it can get. Got cancer? Toss up between succumbing to the disease or the beating chemo gives your immunity. Need bowel surgery? You probably won't make it. Organ transplant? Nope.
posted by kjs3 at 11:02 AM on April 30 [1 favorite]


No, but a healthy lifestyle could save you from a life-threatening case of pneumonia.

You could lead a very healthy lifestyle, but until you live in a climate-controlled corporate arcology, you'll still have to breathe the same air and drink the same water as the rest of us, and a lot of opportunistic infections arise from physical stresses on the body that have environmental causes. As our shared air and water quality worsen, these increase the risks of associated diseases.

I'm not going to name the drug company, but they are a multi-billion dollar multinational that you've likely heard of. Their long-term research focus is on medicines that deal with pulmonary (breathing) disorders like asthma and COPD, mainly because their best-selling drugs treat these diseases in countries like China and India, where pollution is chronic and pervasive.

Basically, this company is betting long on global particulate pollution continuing to increase and being around long enough that they can make a lot of money off drugs to treat symptoms for respiratory disorders.

Global particulates are just one example, but they are on the rise and diseases associated with that kind of pollution are raising mortality rates. Some of those diseases include pneumonia directly, but they also include cancer and pulmonary diseases, which themselves carry increased comorbidity for diseases like pneumonia (cite).

A lack of working antibiotics will reduce our ability to fight off opportunistic infections, which will certainly mean increased deaths, even if we all stop eating meat and start eating vegetables.
posted by Blazecock Pileon at 11:03 AM on April 30 [3 favorites]


My point is if antibiotic use in food animals is contributing to antibiotic resistant infections in humans, as it appears to be, then cutting back on antibiotic use in food animals could potentially have long-term benefits. Unfortunately that would cut into the agricultural industry's profits, which makes these changes unlikely.

It's going to be a tough road but the US does plenty of health and safety regulation despite industry opposition and it often works very well.

Another barrier besides industry opposition is simply that people don't want to reduce the amount of meat they eat or pay more for it but it seems like our current production methods just shouldn't be continued. I'd be more worried about the voters than the lobbyists on this. People don't like making major lifestyle changes because of government policies, some even freakout if they have to switch light bulbs and food choices are way more personal.
posted by Drinky Die at 11:10 AM on April 30 [1 favorite]


I don't get the Tea Party/OWS rhetoric here. Antibiotic resistance is a complex problem, with some aspect of "the tragedy of the commons."

The tragedy of the commons: literal textbook example of why collectivism is necessary
posted by showbiz_liz at 11:12 AM on April 30 [4 favorites]


But I love antibiotics. :(

Yesterday I went to the doctor after two months of persistent wet cough I had been ignoring, thinking it was a viral infection. I took two doses of antibiotics last night and immediately feel so much better, my energy is up and I can breathe again. And my throat doesn't taste like death anymore. And I'm definitely not the type of person who is hypochondriacal at all or goes to the doctor at the drop of a hat.
posted by quincunx at 11:13 AM on April 30 [1 favorite]


The FDA attempted unsuccessfully to withdraw penicillin from animal feeds in 1977, after a 1969 report indicated that the practice may be creating bacterial resistance.

Hard for me to believe that Big Ag and their regulators (who are usually indistinguishable) didn't see this coming and/or did everything they could do to slow it down.
posted by RobotVoodooPower at 11:16 AM on April 30 [7 favorites]


anonymisc: "Phages are more bacteria-specific, which is incredibly targeted and useful compared to antibiotics for some uses, but for other uses (such as general prophylaxis against infection during surgery) that specificity is a problem."
I guess I am metafilter's friendly local phage biologist.

Bacteriophages can actually effectively fill this niche, and do routinely as a demonstrably effective part of the standard of care in much of the Former Soviet Union, but won't and maybe shouldn't. There are currently three treatment strategies for using phages to combat disease in spite of their disastrous yet exciting specificity.

The first is to pre-generate cocktails of vast numbers of phages as they do in the Republic of Georgia at the Eliava Institute and BioChimPharm. At Eliava, they have three cocktails of phages that they update every 6 months against strains that they collect from around the country and don't really have a way to keep track of the functionally infinite number of phage strains that have been evolving in the cocktail since the 1930s. The first is intestiphage, which targets 20 different types of gastrointestinal diseases. One well-controlled trial of the concept was conducted in Tbilisi on 30,769 children back in the sixties, neighborhoods were split up with one side of each street treated prophylactically with a phage cocktail and the other a placebo. The result was a 3.8-fold decrease in dysentery incidence. A second cocktail, pyophage, is made against Staphylococcus, Streptococcus, Pseudomonas, Proteus, E. coli, and Enterococcus, the 6 major causes of purulent infections, it is used prophylactically on surfaces and wounds on a routine bases during surgery and for severe burns as well as against actively purulent wounds (like MRSA) with a high success rate. During the the most recent couple of wars there, soldiers carried spray bottles of phage for gunshot wounds and maintained shockingly low infection rates. The third is a relatively new one against prostititis.

While this pretty clearly effective against a whole bunch of infections, and is pretty clearly at least mostly safe, but there are good reasons why this strategy will probably never be used in the West. The only reports of adverse effects I've ever seen come from an abstract, for a long lost paper presented at a conference during the time that phage technology was considered a military secret, that described injecting volunteered conscripts with 106 times the therapeutic dose, which is generally applied topically, and they only got fevers; but there are very important theoretical harms. Many strains of pathogenic S. aureus as well as E. coli O157:H7 of Jack in the Box fame, Shigella, cholera, botulism, diphtheria, scarlet fever, and a whole bunch of described shrimp and insect diseases are in a sense not really caused by those bacteria but by the phages that infect them. Essentially, all "live" phages can go through what is called a lytic life cycle when they infect a cell, shut down host metabolism and substitute their own, replicate their DNA, construct and pack viral particles, and then lyse the cell for the new particles to hunt for more cells. This is obviously extremely lethal, which is great for us, but some phages (known as temperate phages and somewhat analogous to retroviruses) can also go through a lysogenic life cycle where instead of shutting down the hosts' metabolism, they turn off their genomes and wait. This creates what are call lysogens, sort of a phage/bacteria hybrid, where the phage hides and lets the host replicate it with its own chromosome when it divides. Now these temperate phages have an interest in their hosts doing well and sometimes have exotic genes, which get expressed independently of the host lethal ones, that often contribute to host success in weird situations, like pathogenesis. Thus, for example, cholera isn't really caused by Vibrio cholerae like you may have heard but instead by the CTX-φ and TLC-φ phages. Vibrio are, for the most part, planktonic marine bacteria content to scavenge for low levels of organic substrates in the oceans and leave us well enough alone. However, when infected by the temperate CTX-φ and TLC-φ phages, Vibrio cholerae suddenly gets a pathogenicity cassette of DNA with a type IV pillus and the profoundly nasty cholera toxin. Vibrio cholerae is like the pleasant dude who rolls around on the back of a truck in a jumpsuit picking up the garbage in front of your home, CTX-φ is the agent that turns him into a poison-syringe/grappling-hook wielding madman looking to feed off of your guts. These kinds of phage that are capable of going through this secondary type of lifecycle are pretty trivial to detect and avoid with pure phage stocks using modern sequencing but, while it is clear that the classical microbiology the Eliava uses strongly selects against them, there is absolutely no way to guarantee that they are not present in their ancient preparations even if they've never been reported.

There is also what they do in Wroclaw, Poland at the Hirszfeld Institute of Immunology and Experimental Therapy though. There they treat intractable infections resistant to all other treatment methods with phage preparations that are specifically designed for the strain causing the infection by isolating phage specific to the infection in question. They have success rates that range between 50% and 100% of cases, depending on the type of infection, and publish their findings in English. They suspect that the relatively low success rates with some kinds of infections has to do with the fact that most infections, by the time they see them, have had months, and more often years, to develop solid biofilms and avascular hiding places.

The solution favored by Western companies, the current front runners being AmpliPhi Biosciences taking the capitalistic approach and Nestle taking the socially responsible approach, is to isolate and characterize >5 phages with unusually broad host ranges. Indeed, a cocktail like this is now being used in just about all pre-cooked "ready to eat meats" (think baloney) on grocery store shelves now to prevent Lysteria and prolong shelf life. If you'd like a more in depth, but still accessible, run down of where we are as a community, where we've come from and where we're going; the best review at the moment is still one that I posted as a project a while ago.
posted by Blasdelb at 11:18 AM on April 30 [104 favorites]


If you think viruses are affected by antibiotics, you are part of the problem. Please, get educated on this.
posted by achrise at 11:23 AM on April 30 [2 favorites]


yeah we're probably f'd.

anything an average chump can do for this in the meantime? (continue to) stop buying soaps with antibiotics? don't take antibiotics for bacteria-related sicknesses unless really super necessary?
posted by ghostbikes at 11:23 AM on April 30


achrise, no idea if you're replying to my post or not, but in case you are- it is common to get a bacterial infection following a viral infection, and while rarer, it is also possible to get a bacterial infection that mimics the common cold. I waited for months because I knew this, but the doc concurred it is abnormal for most viral infections to last that long. I can see why it is confusing for many people though. On top of that, you can get both at the same time if you are woefully unlucky.
posted by quincunx at 11:28 AM on April 30


While this pretty clearly effective against a whole bunch of infections, and is pretty clearly at least mostly safe, but there are good reasons why this strategy will probably never be used in the West.

Why can't we have the phages? Just capitalist wickedness?

I know some phage researchers and I have been consoling myself by thinking that phages may help with the antibiotics situation.
posted by Frowner at 11:31 AM on April 30


I'm sorry my crazy partisan rhetoric was unclear to you in this matter.

Well, technically speaking, it was bipartisan rhetoric, but I still disagree that lobbiests and Big Ag are the primary cause of antibiotic resistance.
posted by KokuRyu at 11:33 AM on April 30


It may have been directed at me, since I mistyped 'viruses' when I meant to write 'infections,' and missed the edit window. But thanks for the snark, no education needed.
posted by agregoli at 11:37 AM on April 30 [1 favorite]


Well, technically speaking, at no time did I assert that either of those things were the primary cause. I was responding to the comment immediately above mine which asked, in essence, "why hasn't an extremely wealthy individual with a personal reason solved this problem yet".

what other nits shall we pick?
posted by elizardbits at 11:38 AM on April 30 [2 favorites]


To stress what Blasdelb said, phage therapy also runs into issues where many of these highly infectious strains (like E. coli O157 or V. cholerae O1) are heavily phage infected anyway, and phages usually can't infect strains infected with a similar phage. Many of the worst offenders are phage resistant as a result. Moreover, bacteria have ways to fight off phages (CRISPR, restriction systems) so you're still fighting evolution.
posted by lakhim at 11:42 AM on April 30 [1 favorite]


Are we actually going to have an argument about proximate vs. ultimate causation?

Seems to me elizardbits is effectively saying that dumping antibiotics into the biosphere without regard for consequence or even the rules of intelligent dosing is a net negative, but that the short-term benefits to certain parties will tend to cause such actions to continue despite the net negative due to the way political systems are presently structured, and that this is a bad thing generally.

Does anyone actually disagree with that premise?
posted by aramaic at 11:49 AM on April 30 [14 favorites]


Why can't we have the phages? Just capitalist wickedness?

Regulatory concerns. Like Blasdelb mentions, you can buy phage cocktails in Georgia/Russia.

The "West" has been reluctant to explore phages - out of capitalist wickedness as well as safety concerns. One of the big ones is that phages are a biological that can reproduce (with help).

Think "No, that's the beautiful part. When wintertime rolls around, the gorillas simply freeze to death." - unfortunately we don't have a really good way of getting rid of phages if a bunch somehow started doing stuff we didn't like (for example, really really liking our common healthful commensal bacteria - think uncontrollable diarrhea and reduced nutritional absorption, forever. Or ruminant food animals who can't ruminate anymore, or...).

Good point, lakhim - but increasing molecular research on engineering phages (very possible) could re-design phages that bypass resistance (change CRISPR recognizable sequences - just mutate that NGG) or design phages that will activate endogenous latent phages or a whole bunch of other clever stuff.

But for me, it's control - can't think of a way of killing "bad" phages, yet. If you throw in a tet/dox suicide gene or something, it'll just kick it out over a couple of generations.
posted by porpoise at 11:49 AM on April 30 [2 favorites]


Preventing them from getting out of hand is definitely a problem - V. cholerae and E. coli are completely harmless under normal circumstances (and indeed beneficial), and we're beginning to learn that scorched earth treatments often cause more problems than they solve. There's some really clever stuff that can be done with synthetic biology though that gives me a lot of hope.
posted by lakhim at 11:56 AM on April 30


Does anyone actually disagree with that premise?

Someone upthread actually did say that the use of antibiotics in agriculture is one cause, but not the sole cause.

And (with the caveat that I am a layman with a layman's understanding) do disagree with the premise you mentioned, and I would instead say that antibiotic use in general over the last 70 years has cause antiobiotic resistance. From what I understand, the rate of pathogen "evolution" resulting in resistance was unforeseen. And since there is no one organization in charge of funding or finding new strains of antibiotics, we're rapidly running out of defenses.

Obviously what's needed is strong government support for research and new drug development, because no private company works for charity.

But god bless Bill Gates for his malaria work.
posted by KokuRyu at 12:26 PM on April 30 [1 favorite]


I'm not sure I'm following you, KokoRyu, but you seem to be suggesting that misuse of antibiotics isn't the significant problem here. Evolution is inevitable, and the problem is that we aren't developing enough new antibiotics. And I'm about as lay a layperson as could be, but that's really not my understanding of the situation. Misuse of antibiotics is significantly contributing to the rise of drug-resistant diseases. It's just that misuse of antibiotics isn't limited to agriculture. It's also caused by the fact that antibiotics are available over-the-counter in a lot of parts of the world, and by the fact that doctors in places like the US often prescribe antibiotics for things that don't require them, and by the fact that patients sometimes stop taking antibiotics as soon as they feel better, when they need to finish out all the drugs they've been prescribed. Even with a robust program to develop new antibiotics, there's no guarantee that will happen soon and often enough, so we need to all get together and figure out how to prolong the effectiveness of the drugs we have.
posted by ArbitraryAndCapricious at 12:37 PM on April 30 [1 favorite]


Thanks for tonight's nightmares, everybody!
posted by Camofrog at 1:01 PM on April 30 [4 favorites]


From what I know, sure misuse is an important contributor to the problem, but the thing is pathogens are going to develop resistance to antibiotics no matter what over time. I was also irritated (sorry) at how this post took turn to a US-centric TP/OWS/populalist political debate about the 1%.

However, perhaps a more informed person (than me, anyway!) would like to weigh in here.
posted by KokuRyu at 1:18 PM on April 30 [2 favorites]


but the thing is pathogens are going to develop resistance to antibiotics no matter what over time

Entropy will also destroy the universe over time. Therefore, nothing we do is of any consequence whatsoever. Yay!
posted by aramaic at 1:23 PM on April 30 [1 favorite]


I don't understand why if I am answering a question in good faith I get a snarky answer in return, as though I am a stupid idiot.
posted by KokuRyu at 1:35 PM on April 30 [6 favorites]


I guess I plead guilty to also believing that even correct usage of antibiotics leads to resistance. Certainly agricultural use and over-prescription more generally don't help, but wasn't this situation sort of inevitable?
posted by mrbigmuscles at 1:40 PM on April 30


If I can parse the snark into something more intelligent, I think maybe the point is we've accelerated the evolution of antibiotic resistance faster than anyone thought possible.
posted by agregoli at 1:41 PM on April 30 [1 favorite]


CDC warns untreatable gonorrhea could spread like wildfire
posted by homunculus at 2:08 PM on April 30 [1 favorite]


Serious Resistant Infections Increasingly Found in Children
posted by homunculus at 2:09 PM on April 30


skepticallypleased: Either that are pharmaceuticals or the government are going to have get serious about making "designer drugs" that work on a genetic/immunologic level (like you see with all the new "immunologic" medicines in the cancer field).
Isn't this the ultimate endgame for medicine in general? Understanding how bacteria and viruses infect us on a "gears and spokes" level of genes and cellular machinery, and then coming up with ways to sabotage the process? If that's what it is, governments should be investigating this kind of thing like it's a new Manhattan Project. Maybe they could cure all the diseases...
posted by Kevin Street at 2:33 PM on April 30 [1 favorite]


From what I know, sure misuse is an important contributor to the problem, but the thing is pathogens are going to develop resistance to antibiotics no matter what over time... However, perhaps a more informed person (than me, anyway!) would like to weigh in here.

There are a couple ways these pathogens develop resistance. One is through random mutations that accumulate over time, which sidestep the mechanisms by which antibiotics attack germs and thus confer immunity.

Another way is through selection of pathogens that already have resistance, which can survive environmental exposure to natural sources of antibiotics, but also pass the genomic source of their resistance over to other bacteria in a manner that is somewhat analogous to sexual reproduction.

These evolutionary processes would normally happen on a timeframe that is very long, over many many thousands of years, so strictly speaking you are correct.

However, globalized misuse and overuse of antibiotics, as well as the broad travel of hosts and vectors for disease are factors that, when combined, bring together non-resistant and resistant bacteria and allow this process to speed up on the scale of a few decades to a few years.

The problem is that we have sped up this evolutionary process, and the timeframe that germs now operate on is outpacing our own technological progress on countermeasures.

Will we have replacement drugs on hand to deal with serious infections, when antibiotics cease to work? We are making progress on replacements, but the timeframe for that is not a given. Until then, what human processes and behaviors can we change to slow down the development of resistance and contain pathogens that are already resistant?
posted by Blazecock Pileon at 2:57 PM on April 30 [3 favorites]


old-fashioned artisanal chicken will cost as much as today's beef

I think chicken was a luxury item (in the USA) until sometime after WW2. Maybe not luxury, but older idioms suggest that a chicken dinner was a special event.
posted by thelonius at 3:04 PM on April 30 [1 favorite]


Frontline
posted by j_curiouser at 3:40 PM on April 30


There's an old European proverb: when a peasant eats a chicken, one of them is sick.
posted by Joe in Australia at 4:12 PM on April 30 [2 favorites]


I've changed pediatrician a few times merely due to attempts to prescribe my child an antibiotic for a virus. I've always called the doc out on that, too.

Ya know, I'd like to say to future generations (if we have any) that, facing human crisis of food, of antibiotics/anti-vaxxers, and of climate changes, I did my part to try to make the world better. I've spent much of my life politically and environmentally active, let my kids eat dirt without coating them in germicides, watched out for the herd and not just my own, made many conscious decisions to lesson my carbon foot-print, etc.

None-the-less, our descendants are not going to be impressed, I'm sure. It's really depressing.
posted by _paegan_ at 4:45 PM on April 30 [2 favorites]


Several people upthread have been saying "Tea Party / Occupy Wall Street" as though those groups had similar goals. I do not believe Tea Party supporters would be in favor of increased government regulation of industrial agriculture. Not liking government regulation of anything is their whole shtick.
posted by justsomebodythatyouusedtoknow at 7:16 PM on April 30


Can we move away from the OWS/TP thing and back to holy shit, it's getting super hard to kill bacteria, super fast, and nobody's really throwing tons of time and money at finding new options?

Because that is fucking terrifying. Some sort of international coalition needs to throw Bill Gates levels of money at this problem and fuck the profits.

Like, seriously, when these things stop working we're back in the 1800's, in many ways.

Couple this kind of resistance plus the spread of anti-vax (not that I want to have that particular argument here) and there's a lot of medical ugliness ahead for humanity. Bacteria and viruses fighting back in scary ways.

I'm off to watch kitten videos or something because fuck.
posted by feckless fecal fear mongering at 7:50 PM on April 30 [5 favorites]


Here's a really good article on raising chickens without antibiotics:
The Future of Chicken
How to mass-produce meat without breeding killer microbes.

posted by Joe in Australia at 9:50 PM on April 30


Ah good, I had almost run out of innovative apocalyptic scenarios for my nightmares.
posted by salvia at 10:09 PM on April 30 [3 favorites]


KokuRyu: "From what I know, sure misuse is an important contributor to the problem, but the thing is pathogens are going to develop resistance to antibiotics no matter what over time. I was also irritated (sorry) at how this post took turn to a US-centric TP/OWS/populalist political debate about the 1%.

However, perhaps a more informed person (than me, anyway!) would like to weigh in here.
"
Antibiotics generate resistance because they exert so much selective pressure they empty out an ecological niche and then, on a population level, leave the sensitive critter right next to the niche, taunting it, until resistance is gained and the critter can return. The development of resistance is an evolutionary inevitability, and pretty much always happens within a year or two of introduction, however the quality of management is not inevitable. If we used antibiotics less often when alternatives were available that would reduce the chances for resistance development, if we had better more universal healthcare on a global level newly resistant strains could be detected and aggressively treated before they spread, if science education were more available and public health more valued fewer people would stop their antibiotic regimens mid course when they felt better but before new strains with partial resistance were wiped out, and with a development pipeline that wasn't broken by the failures of capitalist models we would still be getting more antibiotics.

This isn't something that needs to be a problem, but it is something that is going to be a problem anyway.
posted by Blasdelb at 1:21 AM on May 1 [4 favorites]


You guys. You had to do it, didn't you? I saw this report on the news yesterday, and it thoroughly depressed me. I had to go through and hug my partner and almost woke my son up to do the same. This is a genuinely terrifying prospect....

...and you had to remind me about it again. You guys. For the record, i've not read your comments. Hell no. Unless anyone has an answer...? Anyone?
posted by trif at 2:50 AM on May 1


Perhaps this question only highlights my lack of understanding of this topic, but when medical professionals prescribe preventative antibiotics when someone has a virus, as a way of preventing a secondary infection, is that a contributor to this problem? Is that considered overuse?
posted by inertia at 10:25 AM on May 1


trif: "Unless anyone has an answer...? Anyone?"

I just attended a super fascinating lecture that was about an approach to drug design that may have a partial answer.

(Disclaimer: I am an undergraduate level pre-med student. I am not a biologist or a biochemist. Others undoubtedly have more in-depth knowledge, and I may make errors in my description of this topic.)

The lecture, "Drug Design from Transition State Analysis" was by Vern L. Schramm, chair of biochemistry at Albert Einstein College of Medicine in the Bronx. This method of drug design has a ton of applications, not just against bacteria, but that's the only part I'm going to describe here.

Traditional antibiotics kill the bacteria that are causing the infection, by interfering with some process that is necessary to life for that bacteria. (Penicillin, for example, prevents bacteria from constructing their cell walls. No cell wall → no bacterial cell.) Killing the bacteria is the goal, but it's also what allows antibiotic resistance: if any bacterial cells aren't killed by the antibiotic because of some genetically conferred resistance, those cells can still multiply. Now the only bacterial cells left are the ones that are resistant.

One method to solve this problem is to find drugs that will stop the ill effects of the bacteria without killing them. No killing means preventing the evolutionary pressure that causes antibiotic resistance.

This approach could be used against pathogenic bacteria which rely upon a trait called quorum sensing to induce their pathogenicity. Quorum sensing is super interesting: essentially, bacteria that use quorum sensing send out a particular chemical signal to indicate their presence, and in turn can detect how much of that chemical signal is in the environment around them. If the concentration is above a certain level, that indicates to a bacterium that there are enough bacteria of its species present to perform a certain function. Bacteria use QS for many functions: biofilm formation, motility, symbiosis, and even bioluminescence!

(An important researcher in this field is Bonnie Bassler, whose TED Talk "How Bacteria 'Talk'" [transcript] is a good general-audience oriented intro to quorum sensing. A more scientific intro can be found in this paper: Miller, M.B.; Bassler, B.L. (2001). "Quorum sensing in bacteria". Annu. Rev. Microbiol. 55: 165–99. [PDF])

For this topic, though, we're interested in bacteria that use QS for virulence. Vibrio cholerae, the bacteria that causes cholera, is one such example. The thing that makes quorum sensing such a good target for disruption by a drug is that it is not necessary for bacterial life. If you prevent Vibrio cholerae from participating in quorum sensing, they go on their merry way, living perfectly well, just without flipping the switch that says, "Okay! There are enough of us here! Turn on virulence now!" Since the bacteria aren't killed, there is not evolutionary pressure to cause drug resistance.

So! How does Schramm propose to disrupt quorum sensing? By inhibiting an enzyme that is necessary for QS.

Enzyme inhibition is actually a really common way for drugs to work: about 1/3 of all drugs are enzyme inhibitors. The thing that makes Schramm's approach so cool is that he's inhibiting enzymes in a new, and extremely effective, way: he's harnessing the transition state, a fundamental step in the process of how enzymes work. (Here's an article for general audiences about Schramm's research. Here's another general-audience article, this one specifically about the potential of this research with regards to drugs that don't trigger resistance.)

All enzymes take some starting material (a substrate), and perform a chemical reaction to change that substrate into a different material (a product), without changing the chemical composition of the enzyme itself. The enzymes can be reused, over and over. Schramm studies the midway points of enzymatic reactions: the transition state. The transition state is the point in the reaction where the substrate is no longer the substrate, but it's not quite the product yet, either—it's chemically distinct from both of them. Transition states, by definition, are very unstable. But they're also the chemical structure that the enzyme binds to best—far better than the substrate or the product.

What Schramm does is take advantage of this fact to create substances (transition state analogues) which mimic the transition state, but which are chemically stable: like the normal transition state, the enzyme binds to this substance really well, but unlike the transition state, the analogues don't fall off the enzyme as substrate or product. Find the right analogue, and you can plug up all of a particular type of enzyme, to an ENORMOUS degree. In a normally functioning enzyme, substrate is processed into product many, many times per second; transition state analogues bind so well that, in a biological setting (i.e., when used as a drug), they don't fall off for days.

So, if you find the right transition state analogue for a particular enzyme whose product is necessary for quorum sensing (Schramm's research team targets the MTAN enzyme, present only in bacteria, which is part of this pathway in Vibrio cholerae, among others), you can prevent bacteria that use QS for virulence from becoming pathogenic over a long period, without inducing resistance.

Quorum sensing is only one enzymatic pathway bacteria use; you could theoretically use transition state analogues to block any enzymatic pathway you want. However, developing transition state analogues—and making sure they don't adversely affect humans!—is a long and tedious process. We're still quite a ways away from this kind of drug being available on the market for antibiotic purposes. Additionally, this method won't solve the resistance problem for bacteria that must be killed to stop their ill effects—you could use it to kill them by inhibiting some necessary enzymatic process, but then you still have the problem of evolutionary pressure that leads to resistance in the first place.

But still, super cool, right?
posted by ocherdraco at 12:57 PM on May 1 [8 favorites]


I think chicken was a luxury item (in the USA) until sometime after WW2. Maybe not luxury, but older idioms suggest that a chicken dinner was a special event.

Winner, winner, chicken dinner? I wonder now if the alleged curative properties of chicken soup are the result of its former luxury status.
posted by Thoughtcrime at 3:20 PM on May 1


And yes, various agriculture lobbies are arguing that the science is not settled and more regulation is not required. "Currently, there is no evidence that the use of antibiotics pose any health risk to consumers." As far as I can tell, this is classic denial.

These are Canadian examples, but I've heard US agriculture association representatives say similar things.
posted by sneebler at 4:40 PM on May 1 [1 favorite]


I was just wondering whether if, after we've burned through the low hanging fruit in this area, if the next generation of treatments for infections, etc. will be less selective as toxins and that antibiotic treatments will become much less pleasant. Like a low level sort of chemotherapy -- that sort of experience for the patient.
posted by Trochanter at 8:21 PM on May 1


Frowner: "Why can't we have the phages? Just capitalist wickedness?"
Capitalist wickedness has certainly been a large component, particularly in the mid 90's when there were some truly and irredeemably villainous characters trying to exploit phage, but really nowadays its only one of our smaller problems. Phage therapy is, in addition to something that could do a hell of a lot of good if exploited just right, a massive fragrant goldmine that has a great way of getting people with money excited but also unfortunately has a way of filling the heads of the more foolish with ideas of phage as their Microsoft. Having now been around in the community for a little while, it has been pretty sad watching a couple of promising companies and primary investigators hollow themselves out with greed and blind ambition like petty Heisenbergs as they alienate everything that made them promising in their vain attempts to own it all. Even when that is going well though, there is still the omnipresent incompetence at the top of major pharmaceutical companies. These days how fundamentally new kinds of treatments get developed is that they get cobbled together by small start-ups who take on the risk and then, if things start to work out, major companies with the resources to produce and market the products will buy them up for stupid amounts of money. This all makes a whole bunch of good kinds of sense however, over the last decade or so, most of the big players have developed really bad habits of waiting until they reach a point where they've got tons of cash and a big patent that's about to run out, desperately buying something cool that they don't understand to make themselves feel better about their patent cliff, and then promptly forgetting about it. This ends up working out beautifully for everyone involved in the decision where the start-up directors get stupid rich from the buyout and executives get to pat themselves on the back for being innovative while its only shareholders and patients who get fucked. This is only one of our problems though, and whining about the way the world works is not going to help us change it.

The regulatory environment is really our biggest problem as a community, by which I do not mean regulators or their approach to regulating, but us and ours. I've been in the room with people from the FDA sent to communicate with us about what makes sense in terms of constructing a regulatory system that can be built for commercially sold phage, and just the way they saw right through our bullshit to where we needed to be but weren't was deeply impressive. While the Soviet model for phage therapy is almost certainly mostly safe and almost certainly generally effective against a wide range of infection types, we need to get over how it is never going to be appropriate to provide to patients on a routine basis in a Western context as well as how the reasons for this are not bad ones. Here is a review with the most important papers capable of convincingly demonstrating safety and efficacy for the Soviet model, and I find them convincing - I'm the third author, but they are no where near the kind of convincing that is and should be necessary for regulators and never will be. So long as we are starting over from scratch secure in the knowledge that there is somewhere worth going, which we are if indeed we're doing anything, we can do it with characterized phages, we can have a much better idea of what we're doing, and we can do it with modern tools.

That said, we can also already have the phage, but only for people who well and truly need it. Both State and Federal regulators have so far been either understanding, enthusiastic, or manifestly indifferent about physicians providing Georgian phage cocktails on a compassionate use basis, where unproven medicine is provided for life-threatening infections in which there are no proven alternatives. There has been a physician in Texas doing this for chronic MRSA infections since the 90s and now there is a podiatrist in Washington State doing it for diabetic foot ulcers. In Washington and Oregon there is also, separately, a set of peculiar state laws that allow Naturopaths to use medicines that are part of the standard of care in other countries, which are being used to justify providing phage against various intestinal complaints. However, while this is important for developing physician skill, as well as obviously the tremendous effects it has had on patient lives, it is not the goal. Really the end game we need to be shooting for is an industry with more than one company competing to produce prescribe-able products, an academic community capable of supporting that industry with useful knowledge from basic research, and a regulatory system that resembles the one we currently use for live virus vaccines.

If indeed we can make phage therapy work in a western context, this is how we'll do it. If each individual phage is thought of as an untested drug, then each individual phage will need to go through Phase I through III trials that run into the tens to hundreds of millions of dollars. This isn't feasible to do every six months like they do in Georgia, but we will need to do it on some time frame because phage cocktails will generate phage resistance in infectious populations. While we will need to have a way to add new phage from the functionally infinite supply provided by nature, we can't, and shouldn't, just add phage to cocktails blindly. What we want is a system like exists for the flu vaccine, which was created because the process for making the flu vaccine is generally known to be safe, and the risks involved in making the vaccine are generally known. Thus for the flu vaccine the FDA can feel comfortable with expedited testing for each new annual formulation that looks specifically for the things we know could be wrong rather than testing for the unknowns that we wouldn't know in something that was genuinely new. To get there, however, the FDA will absolutely require us to be able to prove to them that we have processes for adding new phage to existing cocktails are generally safe and effective - which is going to be expensive and uncertain.

For an idea of how we're working on it here are some talks given at the conference before last,
David Harper's talk at VoM Brussels in 2012 (17:05)
Regulatory and clinical challenges with respect to phage therapy

Gilbert Verbeken's talkat VoM Brussels in 2012 (16:51)
Bacteriophage therapy: analyses of specific legal hurdles in the current regulatory frames

Dan Neilson's talk at VoM Brussels in 2012 (39:37)
Talking about his phage based enzyme therapy, a good introduction to the concept.
While these two papers really represent the two ways forward being pursued at the moment, leaving aside the often mysterious and occasionally bullshit-full stuff happening around the military,
The role of regulated clinical trials in the development of bacteriophage therapeutics
Antibiotic resistance is now recognized as a major, global threat to human health and the need for the development of novel antibacterial therapies has become urgent. Lytic bacteriophages (phages) targeting individual bacterial pathogens have therapeutic potential as an alternative or adjunct to antibiotic use. Bacteriophage therapy has been used for decades, but clinical trials in this field are rare, leaving many questions unanswered as to its effectiveness for many infectious diseases. As a consequence bacteriophage therapy is not used or accepted in most parts of the world. The increasing need for new antimicrobial therapies is driving the development of bacteriophage therapies for a number of diseases but these require the successful completion of large-scale clinical trials in accordance with US FDA or European EMA guidelines. Bacteriophages are considered as biological agents by regulatory authorities and they are managed by biological medicinal products guidelines for European trials and guidelines of the division of vaccines and related product applications in the USA. Bacteriophage therapy is typically an ‘active’ treatment requiring multiplication in the bacterial host and therefore the factors that govern its success are different from those of conventional antibiotics. From the pharmacokinetic and pharmacodynamic points of view, time of treatment, dosage depending on the site of infection and the composition of the bacteriophage formulation (single vs multiple strains) need careful consideration when designing clinical trials. Scientific evidence regarding inflammatory effects, potential for gene transfer and phage resistance, need to be evaluated through such trials. However purity, stability and sterility of preparations for human use can be addressed through Good Manufacturing Practises to reduce many potential safety concerns. In this review we discuss the potential for the development of bacteriophage therapy in the context of critical aspects of modern, regulated clinical trials.

What is needed for phage therapy to become a reality in Western medicine?
The current status of phage therapy approaches is reviewed and possible hurdles to a practical medical application of bacteriophages in Western countries are identified as discussed at a recent EMBO meeting on “Viruses of Microbes” in Brussels. In view of the growing antibiotic resistance crisis, a coordinated effort by the public health sector is needed to evaluate the potential of phage therapy as an adjunct to antibiotics.
posted by Blasdelb at 5:43 AM on May 2 [3 favorites]


sneebler: "And yes, various agriculture lobbies are arguing that the science is not settled and more regulation is not required. "Currently, there is no evidence that the use of antibiotics pose any health risk to consumers." As far as I can tell, this is classic denial.

These are Canadian examples, but I've heard US agriculture association representatives say similar things."
It is however complicated by how they are actually right. The use of antibiotics in meat producing animals poses only vague and mostly theoretical risks to consumers. The risks it poses are to everyone in agricultural communities who get exposed to bacteria bathed in all sorts of concentration gradients of the antibiotics used in feed, as well as everyone who they come in contact with, which is everyone. Regulating this correctly is not going to be simple.

That risk is also very dependent on the antibiotic being used, where drugs with wider mechanisms of action or 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 problem can always ensure that their animals get sick. 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.
posted by Blasdelb at 5:58 AM on May 2 [1 favorite]


porpoise: Good point, lakhim - but increasing molecular research on engineering phages (very possible) could re-design phages that bypass resistance (change CRISPR recognizable sequences - just mutate that NGG) or design phages that will activate endogenous latent phages or a whole bunch of other clever stuff.
Craig Venter has a company devoted to doing pretty much exactly this, but its never going to produce anything worthwhile that couldn't also be produced with a week's worth of isolation efforts finding another phage that evolution has already built with a solution.
porpoise: But for me, it's control - can't think of a way of killing "bad" phages, yet. If you throw in a tet/dox suicide gene or something, it'll just kick it out over a couple of generations.
Apparently tea is incredibly effective at destroying the T4-like phages that we're generally favoring, just boiled tea. However, for a phage to be 'bad' it necessarily needs to have things like a temperate repressor, an integrase and an exase that can be tested for with sequencing, it'll produce turbid plaques from lysogenic survivors that you can just look at a plate and see, and those survivors will produce plaques on lawns. We can't control the ubiquitous temperate phage that are already an inherent part of every inch of us, but we can control for them in therapeutic cocktails.
posted by Blasdelb at 6:22 AM on May 2


There's No Financial Incentive to Make the Antibiotics We Need
posted by homunculus at 9:24 PM on May 8 [1 favorite]


Blasdelb: It is however complicated by how they are actually right.

I'd be a lot more optimistic about the societal outcome if you were the one making this argument, as opposed to a self-interested lobby group.
posted by sneebler at 10:53 AM on May 10 [1 favorite]


Most Doctors Prescribe Antibiotics That Don't Work
posted by homunculus at 6:33 PM on May 21


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