For reference, 80% of antibiotics used in the US are used in agriculture [1]. Animals are fed antibiotics to prevent infection, but they’re also fed to animals as “growth promoters” [2].
60% of infectious diseases in humans originate in animals, and 75% of emerging infectious diseases in humans originate in animals [3].
Point (2) is no longer true as of 2017 (in the US, 2006 in the EU) [1]. I'm happy to see the FDA getting on top of this regulation. Now let's end careless spraying of antibiotics on crops. [2]
Re: Point (2), it's going in the right direction, but at least in Denmark it is very much used in a "preventative" manner in the pork industry. It took a dive when the regulation came into effect, but in the last few years not much have happened, and we still have a MRSA problem out of control.
Independent sources say that more than 90% of all farms with pigs have an MRSA infection. The butcheries reported in 2014 that 88% of all pigs was infected with MRSA. Every 1 in 3 pack of pork is infected and weak and elderly people should be careful with pork in general because of this risk.
It seems horrendous that we would give antibiotics to any livestock in an across-the-board way.
Livestock should only get antibiotics if they come down with an infection and are diagnosed and treated by a veterinarian. If a bunch of the livestock would get sick without preemptive antibiotics then I probably don't think that method of farming should be legal, and I would be glad to pay whatever higher prices would be necessary to abolish it.
Infections were not created by greedy farmers. They occur naturally among all animal populations.
Some quick googling indicates that this practice both increases meat production by 10-30%, and protects animals from a lot of suffering, as they spend their lives mostly healthy.
That said, yeah, we can't keep doing this, and we have to pay the cost. Let's just not pretend there is no cost.
I'm not saying we should cease treating sick animals. I'm saying only treat the sick animals individually after diagnosing them. If that's not practical then let's change farming practices until it is.
(I'm not a farmer. I have no idea what the impact of this practice would be. However, as a naive person I definitely would strongly prefer to reserve the medicinal powers of antibiotics for humans or individually-sick animals, not huge animal populations.)
I mostly agree. This is already done in many countries, and farming goes on there.
My only point is that this isn't done by stupid greedy farmers for no reason. It's a practical and profitable practice that has had a lot of short term benefits both for farmers, consumers and even farm animals. But it also has to end.
I've heard the opinion that most antibiotic resistance genes don't seem to originate in agricultural use.
High AB usage is one factor in developing and spreading resistance, but it's way more complicated. For example the resistance genes also have to jump onto a bacterium that is pathogenic...
> I've heard the opinion that most antibiotic resistance genes don't seem to originate in agricultural use.
Maybe true but I don't see the post you're replying to saying that. If you are saying that, a reference to some research showing that would be welcome.
> but it's way more complicated
surely true, but it doesn't mean antibiotic overuse isn't a damn good starting point for resistance to develop.
This does not back up your claim. Much of it is about lack of evidence on which to draw conclusions. That's clear enough just in the abstract. I'll quote from the abstract. Selectively due to length, but I'll try to be fair:
"The three mechanisms considered are as follows 1: direct infection with resistant bacteria from an animal source, 2: breaches in the species barrier followed by sustained transmission in humans of resistant strains arising in livestock, and 3: transfer of resistance genes from agriculture into human pathogens. Of these, mechanism 1 is the most readily estimated, while significant is small in comparison with the overall burden of resistant disease. Several cases of mechanism 2 are known [so it's been demonstrated to happen], and we discuss the likely livestock origins of [some bacteria] it is hard to assess in robust fashion. More difficult yet to study is the contribution of mechanism 3, which may be the most important of all."
To summarise, a little, some known, and we don't know.
From the summary, and again I'm quoting selectively so be warned:
"The limited data available make it hard to quantify the relationship between antibiotic use in animals and the occurrence of clinical resistance. As we have shown, while there is considerable evidence associating antimicrobial use in agriculture with resistant pathogens in livestock and in the food supply, the evidence for human health risks directly attributable to agricultural antibiotics runs the gamut from speculative to scant"
Summary: possible real threat, too little data to evaluate.
Further, again from the conclusion:
"Once these [antibiotic-resistant] strains have emerged, it might be only a matter of time before they cross the species barrier and adapt to living in humans, at which time there is very little regulation of agriculture can do to prevent their persistence in the clinical setting. The greatest value of reducing agricultural antibiotic use now may be in maintaining a status quo that, while far from ideal, is greatly preferable to the alternative."
Summary: we scientists don't know but we have reason to be very concerned.
These are my selective quotes and my interpretations, but I personally don't see that they support your position.
TL;DR: I read the article mainly as saying basically John Snow knows nothing.
Up to this point the link between agricultural AB usage and human pathogenic infections with resistant strains is quite theoretical and has relatively weak evidence.
From the article we may actually want them to be used for treating animals.
Apparently these molecules are very hard to build resistance against. Bacteria evolve resistances to many ABs from scratch in lab conditions. If more is discovered about the mechanism of these two drugs, one could speculate about a potential resistance gene.
Is it enough to "adapt" existing genes in most microbes, like with Penicilline? Is a novel gene, traveling on a vector, required to defuse it (like with Carbapanemes)? Or is it extremely unlikely that pathogens evolve any way to counter it?
The latter could be because the mechanism of action is not trivially countered. You can compare it with patching vulnerabilities. A vulnerability is sometimes not addressable without crippling a business critical feature.
Then we might want to use these drugs in animals and less in Humans, because we know more about how the old drugs work and their side effects.
The original post said farm animals. You're now apparently conflating that with animal testing, which will take place anyway.
Anyway the OP makes a lot of sense. Resistance is known to increase when antibiotics are used. If we use them less (ie. not on farm animals) then it seems reasonable that resistance development will be lessened and the drugs' useful lifespan will be extended.
Much as I hate to say it, speaking as a veggie, farm animals are a commodity and moderately expendable.
I've never been convinced of the argument that using antibiotics, causes them to be less useful. Does doubling the use frequency increase the probability of a resistant bug? How much? And how much does that reduce the useful lifetime of the drug? I'm thinking, 10X the application might reduce the useful lifetime by months out of decades. Maybe not the issue its been blown up to be.
Do you have an argument for this, or is it just gut feel?
The argument for the standard view is simple: The more "bugs" are exposed to antibiotics, the more opportunity/reason they have to develop resistance to it.
But its a multivariate problem space. Exposure is just one of the variables. Others (mutation rate, types of host, cross-infection rate etc) are also important and highly non-linear.
It's a big-data problem - what are the regression stats for each independent variable? And is 'exposure' the important one?
...and without data it seems clueless to be castigating folks for using the tools we have now, to accomplish goals we have now.
If our current antibiotics are becoming less useful, then create new one. There's nothing magic about the ones we're using now. They were just the first ones we came across. Like VHS vs Betamax. Lets get on with it.
I castigated no-one for this. I didn't suggest not developing new antibiotics. Far from it. Merely that we use new and old ones wisely. That, and make decision based on data.
Antibiotic management is an ongoing topic and effort, but you can't make independent countries comply.
Also, the amount of antibiotic used is not as much of a problem for AB resistance as some people using the "as candy" metaphor may think. The epidemiology of AB resistance is way more complicated, as the spreading of resistance requires multiple factors to coincide. Like the right resistance gene, the right strain, infection chains etc
Honestly I like that better than the US version of requiring you to pay a bunch of money for a doctor to sign off on something that a pharmacist should be able to give upon request. Something like an eye infection should be just a couple bucks to treat, but just going to a doctor to tell you "yeah your eye is infected, you need antibiotics" and then getting charged $100 or more for their signature is crazy. Maybe it would work fine in a free healthcare model. From the research ive seen there is very little risk from humans abusing antibiotics, especially in comparison to agricultural usage. I can go to the store and buy amoxicillian for fish for like 5-10 bucks, but to get a human prescription it could cost $200+.
Unfortunately, at least in poorer countries, people will simply disregard the license. Indian/Chinese/Russian pharma companies are quite good at synthesizing patented compounds (after all, the relevant information is in the patent claim) and selling them for cheap.
And even in industrialized countries, crooked vets have abused reserve antibiotics not intended for animals.
Antibiotics don’t work on humans. They work on bacteria in humans. Your sentiment is generally correct for most other types of medical research, but antibiotics generally pass the human testing fairly easily, provided that they don’t also kill the human they’re tested on.
I believe we have a responsibility to steward the planet for future generations. Obviously if we all die from infections because we saved all our antibiotics for the future that wouldn't be good stewardship. But the way we hand out antibiotics to prevent a potential infection or to fatten up livestock seems to be a poor use of our resources.
“I’ll piss in my shoe to get warm now. The reduced capacity to keep warm will be me-in-5-minutes’ problem I guess. Yes I should clean up after myself but I should also suspect that future me find the will to survive.”
Story time: A few years ago while I was in Uni, I came down with a sore throat. Strep throat had been going around, so I assumed that was it. I went to the college clinic to get a doctor's opinion and medication. I told him that I thought it was strep, but the doctor wanted to run some tests to see what it was specifically, but he also said, "In the meantime, I'm going to prescribe a large doses of penicillin to get a head start and kill it since it's definitely bacterial." Fast forward a few days and I'm even sicker.
The doctor called saying the tests were negative and we wanted to test to see if it was viral instead. Nothing came back. Then, he wanted to test to see if it was STD, but the tests take longer to come back. While waiting for results and continuing to take penicillin per my doctor's directions, I continue to get sicker. The infection had moved from my throat to my gums, then to my lips, then to a couple of fingers (that I accidentally slammed between a door) and my genitals.
At this point, the doctor is convinced I have an STD because it's on my genitalia despite insisting that it started in my throat. He said it could've been transmitted orally. He runs every STD test under the sun, although he sent the samples in for the wrong tests the first time, and everything comes back negative. Since they all come back negative, he is convinced I have HIV considering how quickly it spread. He orders that test.
A few days later while bedridden and during finals week, I get a call from a new doctor saying the HIV test came back negative and to come in so she could examine me herself. Considering how sick I was and for how long, she said that I clearly should have been hospitalized, despite the previous doctor that I saw nearly everyday and saw how long I had a fever for (2 weeks straight) kept telling me to just get rest. She also said that he never tested for strep throat, despite me insisting that's what I thought it was on the first visit.
The new doctor says that she thinks it's strep throat too (which the previous doctor ruled out without testing) and she runs as many tests against it as possible. Turns out that I had antibiotic-resistant strep throat that became resistant due to the penicillin that the previous doctor was so quick to prescribe to "get a head start". It turns out that the doctor had been fired and she was his replacement...for good reason.
Anyways, antibiotic-resistant infections are no joke. They get real bad, real quick. Plus, a shitty doctor can create it by prescribing medication nilly willy and force a potential HIV scare that you have to deal with for like a week. Those three weeks were the worst of my life, not just because of how sick I was, but also because I was convinced (since the doctor was) that I had HIV, forced to confront the person I assumed I contracted it from, and go through the worst pain in my life every time I had to take a piss.
I don’t understand, how did it become resistant due to the penicillin? And it seems you’re blaming the doctor for this, but penicillin would be the natural first course of treatment here.
I mainly blame the doctor for not testing for strep and the multiple times he was "convinced" it was something else without testing for it. Under no circumstances should a doctor say "I'm convinced you have HIV. The tests will confirm this".
Furthermore, penicillin is only suggested for group A strep, which has already been declining in effectiveness since the 80s. It also shouldn't be given simply as a precaution until you know what bacteria you're dealing with. It was probably already a resistant strain of strep, but the way the following doctor explained it to me was that by introducing the penicillin, it made it more resistant to other antibiotics that I should've taken instead. The only course of action I had was to wait it out. She said she could have tried other antiobiotics, but there was no way to tell if it would work. Luckily, I was already recovering by the time we got the results back for strep throat.
P.S. The person I contracted the strep throat from was fine after about a week of clindamycin.
EDIT: I’m no doctor myself. I’m just going based on what I was told. If the second doctor gave me bad information, then I’ll be happy to assume that both were shitty doctors. That wasn’t the only time I had horrible experiences with that clinic (completely forgot to document multiple doctor’s visits and weeks of PT I had in relation to a sports injury and I lost my redshirt eligibility as a result as there was no proof of the injury). That clinic was the only option I had with student-athlete health insurance. But, I’m not changing my mind on the first doctor after everything else, regardless of the penicillin.
I'm going to go out on a limb here and assume that lab tests for other bacteria need to be cultured as well, such as staph, which he did request labs for. Again, I'm not saying penicillin wasn't appropriate because I'm not a doctor. However, he continued to test everything but the one thing I asked him to, which it turned out I had. As I also said in another comment, he told me to continue using the high doses of penicillin (500mg IIRC) throughout him being convinced I had something viral, then an STD, and then HIV without ever changing the dosage and despite my condition getting progressively worse. There's multiple things I blame him for, the most upsetting being the statement-of-fact that I had HIV when I didn't. I also don't believe he was fired for no reason.
Starting with penicillin is standard practice for some infections - it’s called empiric treatment - you start with the weakest antibiotic and work your way up, you reserve the strongest antibiotics for those cases where the infection isn’t getting better.
In some cases resistance is so widespread that they skip the weakest and just right to the stronger antibiotics.
I'll just refer to my other comment. It may very well have been the right treatment, but I also don't think it's the right move make a patient continue using it and not even change the dosage when it's doing no good. I was instructed to continue to take it despite him eventually moving on to viral, then STD, then HIV, despite my condition getting progressively worse.
The use of antibiotics is actually very institution specific. Hospital usually have antibiotic protocols - the tests that should be run and what drugs are used 1st line, 2nd line, etc.
Antibiotic resistance can be really high at one hospital and really low at another hospital down the street.
He ran tests for staph and something else that I don't remember since it was a few years ago, but strep wasn't one of them. I specifically asked for him to test strep, but he said "That doesn't look like strep to me". I also tried to repeat to him on return visits that the person I thought I got sick from had strep, but he continued with the viral tests and said that the penicillin would have stopped it if it was strep. He told me to continue using the penicillin anyway when he started testing for other things, specifically herpes and shingles (IIRC) due to it becoming a skin infection. I generally don't remember that week very well considering I was trying to study for finals and trying to prepare for a foreign language interview for a class that I was struggling in all year. I just tried to follow his directions and keep my mouth shut after the first week. I really didn't have the energy to do otherwise anyways.
As an introvert and someone with Social Anxiety Disorder, I don't say much (hence my username) and I don't ask too many questions in person. This was also before I got treatment for major depressive disorder and SAD, so I spoke even less then. But, I was at least concerned enough to request he test for strep and to try to insist that I thought it was strep I got from someone else too, which was quickly diminished into disregard each time I tried. I pretty much kept my mouth shut after out of embarrassment. In the beginning things felt questionable, like the staph test (like why staph?), but I stopped questioning after I felt embarrassed. It wasn't until the second doctor that I questioned everything else he did, including the viral tests.
It was a bad experience I had and I'm salty about it. I may be putting blame or wrongdoing where I shouldn't due to said saltiness. A lot of the things he said and did were questionable though and I blame him in the least for making every visit and those 3 weeks as difficult as possible for me, when I feel there were at least some better options he could have chosen and the second doctor confirmed that to me.
No. We shouldn't be wasting resources on developing new antibiotics, because their effectiveness will be relatively short lived. We should focus on alternative sources, such as plants found in rainforests that are rapidly disappearing.
They're not just less useful. You're creating new superbugs in the process. Meanwhile, rainforests are disappearing, which likely have plants that offer sustainable solutions.
You're heading down an unwinnable path with antibiotics, and creating new superbugs. You're running out of time to discover a real fix, because rainforests are rapidly disappearing. So yeah, the analogy is apt.
It's great that there are some new antibiotics, but I don't get this claim that "big pharma" won't develop new cures and only manages chronic conditions.
First, it's factually false. There are now multiple Hepatitis C cures for a formerly chronic (and eventually fatal) disease, let alone all the other chronic conditions that pharmaceutical companies have cured or diminished. And "big pharma" companies have gotten to the same stage as these teams with antibiotics.
Second, it doesn't even make sense unless you treat "big pharma" as a single monolithic entity. In reality, it's many many companies, including startup pharmaceutical companies, all competing against each other. I don't think of bacterial infections generally as chronic conditions in the first place, but if one company makes money on a drug that manages some chronic bacterial infection, there's no reason that another company would be worried about taking away profits from the first company.
Also, the government immediately put price controls on the Hepatitis C cure even though it was already going to be offered at a cost that was way below the lifetime treatment cost of the previous standard of care. This was predictable, of course, but it's weird to blame the pharma companies.
I can easily afford $4000 per month on a mortgage for 30 years. I cannot afford a one-time cash payment of $1M to buy the same house, even though it's "way" less than the lifetime cost of the mortgage.
Essentially no individuals are paying this, regardless. The price controls I am talking about are for medicaid (to which many non-Medicaid prices are indexed).
The argument is that antibiotics are not going to be a attractive target for any pharma, big or small. If you develop a new antibiotic that kills resistant bacteria effectively, it's going to be an antibiotic of last resort, heavily regulated and rarely used. Less profitable. Without government interventions to incentivize development of new antibiotics, I don't believe we'll see pharma take on the challenge alone.
Meanwhile, we've seen that Hep C cures can be (extremely) profitable. See also Luxterna (gene therapy for inherited blindness).
“Big Pharma” specifically refers to a tiny number of huge companies that spend vast sums of money on marketing and buying tiny drug companies and almost nothing on groundbreaking research.
That’s not to say they do nothing of value. A giant companies they are naturally risk averse and aim to maximize shareholder value. Which means their focus is simply on low hanging fruit with still pays dividends.
Developing Cialis and Levitra for example after Viagra was relatively low risk and simply good business. Similarly we have a silly number of drugs that are almost but not quite Morphine. Having options has real value and expanding the range of treatments for common issues improves people’s lives.
You do realize that Pharma companies have the highest R&D spend of almost all industries? And nearly 80% of new molecular entities (breakthroughs) come from biotech/Pharma?[1]
Just the top ones have total R&D spend of almost $40B.
And no, that doesn’t include marketing costs. That’s separate.
Saying that big Pharma doesn’t contribute to new drugs is completely false.
The Development part of R&D has little to nothing to do with research. Thus you can’t equate R&D spending to Research spending. Companies have gone so far as including what is best described as marketing expenses as R&D.
Further, I excluded most companies from the definition, you need to defend them not the industry.
For every new drug that starts in academia, a pharma has optimized that molecule / biological to maximize efficacy and reduce toxicity, always incurring major expense to do so, 90% of the time ending in failure.
Like most 'successes', new drugs arise due much more to grunt perspiration (and regulation) at a pharma, than due to inspiration by a genius inventor — despite what industry outsiders may want to believe.
That optimization generally starts in tiny biotech companies not the industry behemoths. What they lack is less research prowess than the ability to efficiently market to doctors. Thus the win/win of the big guy’s constantly buying up other companies.
Granted, the equilibrium is generally for small companies to try and sell early when some risk still exists.
Say startup company develops drug A that will compete with big pharma drug B which is making billions a year, and envisions it to make 7 billion in the next 5 years. An internal analysis from big pharma calculate drug A could wipe out half of that =2.5 billion. Big pharma buys out the startup for a billion, close them down indefinitely. Couldn’t that happen?
Getting a drug to market is horrifically risky all the way up through approval (and still somewhat risky post approval). ~1/1000 compounds get to market and ~1/100 drugs make it from Phase 1 (first in human/safety) to sale. By the time the odds are decent that a drug will get approved, the sponsoring company will have sunk much of the ~$1 billion it takes to get all the way across the line.
At that point the valuation of said startup is going to be approaching the expected life time value of the drug (less a discount for risk of a late failure and the time value of money). Any acquirer might as well finishing getting the drug and its new patent protection the rest of the way to market.
That startup won't have the couple hundred millions needed to get the compound through clinical in the first place. So, what they do is they team up with "Big Pharma" (I hate that dog whistle) and get royalties.
For the pharma corp. it makes sense as the new antibiotic will also take market share from the competition, so they have a net gain. If they project to lose 2.5bn on their existing drug, spend 1bn for purchasing the startup and make 7bn on the new drug, why on earth would they buy the startup to shut it down?
Drugs only get about 10 years of market time on patent, because drug candidates are patented before they go through clinical development. So this hypothetical drug company might patent the acquisition and start putting it through clinical trials to have something on deck when the original one goes generic
I know there's a lot being said about super bugs...but is the expectation that we just keep developing stronger antibiotics? is this something can be sustained over the next few decades/centuries?
I think if we ever phase out animal agriculture we will be relatively safe. You don't have to worry about superbugs if you don't create places for them to develop, which we effectively do by giving billions of dirty animals low doses of antibiotics indefinitely.
Serious bacterial illnesses in countries with good health systems are already pretty rare. The vast majority of them come from unsanitary food practices
Won't there always be somewhere though? Until we have a fully developed planet with no empty land, there's going to be swamps, tar pits, decomposition in nature and a plethora of other strange things on Earth that could give bacteria places to grow. Not to mention space-bacteria!
If all of our countries with health systems designed for our bacteria aren't equipped to handle more advanced bacteria, wouldn't it take just one explorer to bring back a species-threatening disease?
Sure, but that somewhere would be very unlikely to have antibiotics, making the development of further antibiotic resistance unlikely. Non-antibiotic resistant bacteria is very easy to treat and is essentially a solved problem.
The space thing is irrelevant. You can't develop pharmaceuticals meant to kill things you don't know anything about
It's naive to believe AB resistance is only/mostly created in agriculture.
There is no evidence to that. Even the existence of resistant bacteria in agricultural animals doesn't prove there is a danger for Humans.
In Human tuberculosis for example, resistance seems to happen de novo in Humans, normally, after the patients go through multiple ineffective or aborted rounds of treatment.
Hopefully some knowledgeable can chime in. I was under the impression that in the long term antibiotics will need to be replaced by something else. I'm 42 and just this year I learned (in a mainstream newspaper) about bacteriophages [1] as a means of combating infections. Does anybody know if we are close to seeing widespread adoption of this approach? Is it too costly? Is there a risk that it may get out of control?
The gist as I understand it was that Western medicine bet the farm on antibotics while Russian medicine went primarily towards phages. Because of it's Not Invented Here status, Western medicine was biased against it for ideological and political reasons.
Using phages to treat infections (phage therapy) has traditionally been suppressed in the West, but is making a comeback with a few high-profile case studies in recent years. Tom Patterson had an atb resistant Acinetobacter baumannii infection that was cured with phages [1]. His wife wrote a book about it (The Perfect Predator) that is a good read review of the field. More recently, a patient with cystic fibrosis was cured of a Mycobacterium abscessus infection with phage therapy [2].
These therapies are currently very expensive and time consuming, as they require custom testing of libraries of phage against the specific microbial isolate. There have not been any successful large scale clinical trials yet.
For a good review of the field (but behind academic paywall), see [3]
Good, now let's make sure they're actually not super toxic to humans beforehand rather than lie to people and cover up evidence until public outcry causes them to be taken off the market.
It’s in mice, so no guarantee it survives being used in humans.
Even if it does work in humans it’s likely at least a decade from being safely usable in humans.
And finally: there are already tens of thousands of people dying from previously treatable infections. I would expect that number to be millions eventually
