New antibiotics effective against resistant bacteria in mice
presse.inserm.fr
presse.inserm.fr
60% of infectious diseases in humans originate in animals, and 75% of emerging infectious diseases in humans originate in animals [3].
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638249/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1804117/
[3] https://www.cdc.gov/onehealth/basics/zoonotic-diseases.html
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.
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 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.)
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.
The use of human antibiotics in livestock has already been banned in the US by the FDA.
https://www.thebureauinvestigates.com/stories/2018-12-19/ant...
[1] https://en.wikipedia.org/wiki/Antibiotic_use_in_livestock#Un...
[2] https://www.nytimes.com/2019/05/17/health/antibiotics-orange...
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.
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...
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.
"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.
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.
And even in industrialized countries, crooked vets have abused reserve antibiotics not intended for animals.
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
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.
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.
And I much prefer taking well known antibiotics as long as they work.
Agreed, but you may not have that choice for much longer.
> I'm thinking, 10X the application might reduce the useful lifetime by months out of decades
Possibly, sure. And possibly not. Maybe 1% extra use reduces the drug's working life by 100 times. Without data either claim could be true.
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.
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.
It's a big-data problem - what are the regression stats for each independent variable? And is 'exposure' the important one?
Promising drugs like this a dime a dozen. Proving that they work from this stage is the hard part. This is what big pharma specializes in.
Antibiotics that kill cilia or kidneys or livers are doing something or other to humans, in addition to working on microorganisms.
The R&D landscape is littered with antibiotics that kill bacteria but can’t be used in humans.
Or worse "Resistance to triclosan [not an antibiotic] could lead to resistance to other biocides or antibiotics." https://ec.europa.eu/health/scientific_committees/opinions_l...
Indeed I think this may have been confirmed now.
Heat and/or simple chemicals have to be a better option.
Edit: that study cited is outdated, this is more current and less 'maybe': https://www.sciencedirect.com/science/article/pii/S016041201... is more recent.
https://www.ft.com/content/4da1c6e4-603d-11e9-9300-0becfc937...
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.
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 mainly blame the doctor for not testing for strep
In some cases resistance is so widespread that they skip the weakest and just right to the stronger antibiotics.
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.
(which the previous doctor ruled out without testing)
Then in your second paragraph, you wrote that they tested for viruses, which is generally unheard of for respiratory viruses.
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.
And short term value is still…value.
Gotcha.
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.
Pretty glad my taxes helped pay for that research...
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.
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.
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.
Granted, the equilibrium is generally for small companies to try and sell early when some risk still exists.
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.
[1]https://blogs.sciencemag.org/pipeline/archives/2010/11/04/wh...
Further, I excluded most companies from the definition, you need to defend them not the industry.
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.
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?
Meanwhile, we've seen that Hep C cures can be (extremely) profitable. See also Luxterna (gene therapy for inherited blindness).
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]
[1] https://aac.asm.org/content/61/10/e00954-17 [2] https://www.nature.com/articles/s41591-019-0437-z [3] https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(1...
Serious bacterial illnesses in countries with good health systems are already pretty rare. The vast majority of them come from unsanitary food practices
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?
The space thing is irrelevant. You can't develop pharmaceuticals meant to kill things you don't know anything about
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.
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
For the chronic resistant infections, I'm not sure how many people would be willing to roll the dice.