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Why do antibiotics exist? (asm.org)
143 points by maxerickson 46 days ago | hide | past | favorite | 95 comments



The article makes much of the pairing of antibiotic production genes and antibiotic resistance genes. They often occur on a single plasmid and are passed around together.

But there must be different facets to antibiotic resistance genes, because a bacterium that is producing an antibiotic needs to avoid being poisoned by it. Perhaps some genes produce antibiotic resistance by coding for proteins that metabolize the antibiotic. Such genes are not helpful when paired with antibiotic production because they are destroying the antibiotic as fast as the other genes produce it.

By contrast, some antibiotics work by destroying the cell walls of bacteria. Presumably some antibiotic resistance genes work by coding for resistant cell walls. And a bacterium that is producing such an antibiotic had better have such resistance genes or it will end up destroying its own cell walls.

The article is silent on the differences between antibiotic resistance genes that a producer needs, to survive its own antibiotics, and antibiotic resistance genes that a producer mustn't have, to avoid sabotaging its own production.

The article raises the issue of mutualism between different species of bacteria, with shared resistance and production genes letting the diverse community resist outsiders. Perhaps that is already a complicated story without adding in different kinds of resistance genes.


  > But there must be different facets to antibiotic resistance genes, because
  > a bacterium that is producing an antibiotic needs to avoid being poisoned by it.
Excuse the analogy, but this looks like looking at the problem under a microscope but not looking at the bigger ecosystem.

Every living thing produces materials that would poison it. We exhale carbon dioxide, our solid excrement is often toxic in addition to a biohazard. Even the skin cells we shed and sweat would be problematic if left to accumulate.


> In reaction to the antibiotic resistance problem and with treatment options dwindling, public health officials attempted to control antibiotic usage as a means of controlling resistance (20). The expectation was that rates of resistance would diminish as antibiotic usage dropped. However, resistance persisted even in the face of such drug management practices on both small and large scales (20–23).

This makes perfect sense to me. Why did this not work? The article continues with an explanation of "the ecological fallacy" but I don't understand how the two are supposed to be connected.


The problem is that there was a very compelling "just so" story that antibiotic-resistant bacteria are inherently at a competitive disadvantage vs. susceptible bacteria absent selective pressure.

Take the antibiotics away, and the resistant bacteria will follow.

Unfortunately, microbial ecology is much more complex than that, and it hasn't panned out that way. Often because resistance plasmids also carry other helpful genes. For example, I'm currently working on a study where there's high levels of antibiotic resistance to an antibiotic that isn't used in that population because there's other things hanging out on the same plasmid.

Also note: That's not what most people mean when they say "ecological fallacy", which is a statistics term.


The explanatory gap you're seeing is the difference between equilibrium and dynamic analysis. As time goes to infinity, the probability of an organism retaining genes not useful to it declines to zero. Given enough time, that resistance gene, if not directly beneficial by side effect, will be pruned.

But evolution takes time. If the resistance gene is on a stable plasmid, if the plasmid confers other fitness advantages, and if the resistance gene itself only infinitesimally reduced fitness, then evolution can take a very long time indeed to reconfigure that plasmid and optimize away the resistance gene.

Both camps are right here.


The problem is one of those camps was relying on an equilibrium condition and pretending like it was on a clinically relevant time scale.


Not all proposed evolutionary mechaniams that turn out to be false, much less merely incomplete, are just-so stories. The fact that the hypothesis was simple makes it more reasonable.


Yeah, but this was very much a just so story.


Huh, how? It takes scarce resources for the bacteria to produce many of the structures that protect it from antibiotics. Structures that are unused but require resources are selected against, or at the least decay through mutation. This is an extremely common and simple evolutionary effect.

Are you using "just so" as a synonym for "suspiciously convenient"? That's not what it means.


No, I'm using it to mean an untestable (or in this case untested) narrative explanation for a biological phenomenon. There are several prevalent narratives around the evolution of microbes that are taken to be true because they tell a nice narrative story with very little empirical backing, and even less information on things like time frames.

"Structures that are unused but require resources are selected against" for example, is something that feels correct, but isn't necessarily true because resistance genes don't exist in isolation.

"Community MRSA will lose out to MSSA because of an absence of selective pressure" kept being trotted out because it fit narratively well beyond when it was becoming apparent that wasn't true.


I can't find a way to interpret your use of "narrative" that makes your argument work.


There are so many exiting old antibiotics that might be possible to repurpose however no money or willingness to qualify them https://www.sciencedirect.com/science/article/pii/S1198743X1...

I guess there is no money in requalifying an out of patent antibiotic.


The hypothesis was that resistance mutations would negatively impact fitness (as mutations usually do), so natural selection would prefer no-resistance once the antibiotics are stopped. But instead it looks like once resistance has evolved it doesn’t go away, suggesting that it comes at no cost to reproductive fitness.


Not necessarily at no cost - but not at a cost greater than the advantage of having the resistance, which is still massive since the use of antibiotics is not in fact stopped, just reduced.


From "The Demon Under the Microscope" by Hager--an interesting read on the history of Sulfonamides (the drug that kicks off the "golden age of antibiotics on the chart)--usage was entirely uncontrolled and people did not complete drug regimes. Generally (and I'll probably get this very wrong), that antibiotic worked by blocking uptake of external energy sources.

The drug was tremendously effective and widespread. The book made it sound like all of the strains that did not evolve a solution to that antibiotic were completely wiped out by the evolutionary pressure of the antibiotic.

I'd imagine (just guessing) that even if the antibiotic was stopped, the organisms would not have anything like the evolutionary pressure to change back (and the consequence of getting wiped out by the drug if they did). They probably get along "good enough" or the drift back is slow. In other words, the pressure to change was one of, essentially, absolute survival, while the change back is one of risky convenience.


I'm a little disappointed that this isn't an article about how fungi became the world heavyweight champions of cellular level biological warfare.

I've often wondered if we could let the fungi do the work for us, and maintain colonies that are periodically challenged with organisms of interest, such as ones that have broad resistance, and see what they come up with as a way to create new antibiotics.


Does antibiotic overuse really contribute a large portion of antibiotic use?

I ask because it seems like misuse is blamed for antibiotic resistance: but it seems to me that bacteria don't care whether youre using it legitimately or not: either way has a chance of contributing to resistance.


One thing I hear cited often is the way antibiotics are widely used in animal agriculture to boost margins by helping keep more animals alive in the lowest cost living conditions (often squalid and unhealthy for the animal). This is antibiotic abuse on a massive scale, for the profit of private individuals. :facepalm:


This feels like a pretty low hanging fruit to regulate away. Ban antibiotics use in agriculture in civilized countries and ban importing antibiotics grown meat from the others (I would guess it's easy to test).


It's been this way for decades. IMO it's the main source of antibiotic resistant bacteria.

You have billions of chickens being raised every year, each a Petri dish ready for evolution of resistance.

You have at least 10 billion fresh "Petri dishes" every year. That obliterates human antibiotic use.

When chicken is given an antibiotic, how exactly is that distributed over the body, especially for a sedentary overweight chicken that can hardly walk?

There's no way you can tell that a high dosage will result in no bacteria alive when there can be a pocket of sick flesh where antibiotic might not reach its full potential.

Similarly, the massive rise in UTI infections in women over the years is a side effect of this problem. I do not believe UTI infections in women were that debilitating in the past. Today you can't even get rid of them with antibiotics and a lot of women develop a decade long recurrent UTI infection problem.

Human antibiotics use is not an issue.


The FDA has already been working to reduce antibiotic use in agriculture.

https://www.fda.gov/animal-veterinary/safety-health/antimicr...


I wouldn't call it low-hanging fruit considering just how dependent large-scale animal agriculture is dependent on antibiotics


This would mean either that we would have a lot less food, or we would have to divert a lot of effort from other productive activities to make it up. Maybe that's okay, but still this idea is not free, and not low-hanging fruit.


Not less food, just less meat.


Not just meat, also dairy & eggs. Thats significant.


I like how you don't even contemplate reducing profits as solution (as opposite to mass deaths or mass starvation).


How would you go about reducing profits? If you add costs, the farmers will either pass them along to the purchaser or they will get out of the meat business. That means either higher prices (which should lower demand) or lower supply. In either case it looks like consumers eat less meat. I'm not trying to defend antibiotic usage. I'm curious what a reduced profit solution would look like, maybe I'm imagining it wrong.


I do not see how profits have anything to do with antibiotics and the level of effort required to produce animal products.

Antibiotics allow us to produce animal products with reduced effort per unit than otherwise. If we ban antibiotics, it will require more effort to produce the same amount of animal products. That is true regardless of what happens on the money/profit side. This may be a fine tradeoff, but it's still a necessary tradeoff.


As the article mentions, it's a very sketchy hypothesis that antibiotics help agricultural production by the mechanism of permitting survival in cheaper conditions. Antibiotics actually seems to improve production for other, unknown reasons. We just assume that the mechanism must match the mechanism taken advantage of by antibiotics use in humans, but it looks like there's probably something else going on.

It might be as simple as the antibiotics shifting the balance in the gut towards bacteria that just happen to be more beneficial to rapid growth? That would be consistent with the thesis of this paper, where antibiotics are used naturally to encourage the growth of "compatible" organisms. I wonder exactly which antibiotics are used for agriculture -- if some antibiotics help and some hurt, that would support this hypothesis.


Pig farms in the nordics are under strict animal wellfare regulations which are enforced effectively. Pig farmers also informally experiment with everything from breeding to feed and antibiotics in order to gain every advantage.

As I heard it from an uncle in who raised piglets for decades. There is no visible health difference between two groups of piglets, one raised on antibiotics and one not. Its also worth mentioning that any piglet which gets any severe wound or infection is simply discarded, rather than treated. They still use antibiotics because the piglets on antibiotics gain substantially more weight from the same feed over the same time. In my uncles case, he stopped when the legal loophole closed. But the danes still do.


A major category, ionophores, are used to help ruminants tolerate high grain diets.

There's not really any mystery why that helps them grow of course.


I don't think people are claiming that bacteria care how you're using the antibiotics. It's just that using less antibiotics is better if possible, and it makes more sense to cut out the least important usages first. I mean, if it's between throwing 100 doses of antibiotics into a river or depriving 100 sick people of their dose of antibiotics, it seems pretty clear which choice to make.


It definitely is - both in the developed and developing world there is a staggering amount of overuse of antibiotics.


Coming from India, it's crazy what you can get over the counter. I think that medicine should be more available and cheaper but the fact that you can get so many antibiotics without a prescription is definitely a contributing factor.


From what I've read, it's not even human misuse in India driving the change, rather pharmaceutical factories dispose of their antibiotic-laden wastewater into local rivers, driving an ecosystem level race for resistance.


It's more of a "yes and..." problem. There's also a sanitation aspect to things.


It's because vaccines use your own immune system against the infection. Your immune system is uniquely good at protecting at not just the exact disease but also possible mutations. Flu is (for the most part) the exception because it can do some unusual things.


> Flu is (for the most part) the exception

Flu and coronaviridae.

Shit, thoughtcrime. Hope I don't get vanned.


No, coronaviruses cannot swap out their genes the way the flu can.


> If the secret society system was a dominant selective force in evolving and maintaining antibiotics in the preantibiotic era, then changes in the magnitude, frequency, and diversity of antibiotics after 1940 would likely have caused a consequent shift away from a production-resistance balance in favor of a resistance-dominated evolutionary strategy.

So if bacteria in nature use antibiotics for signalling and to filter surrounding bacteria, rather than for warfare, it's not reasonable to expect humans to stop using antibiotics as warfare against dangerous pathogens (though using it to make animals grow faster is another story). What's the takeaway from this hypothesis?


Bacteria are microorganisms, meaning that they are life forms. The word ‘antibiotic’ breaks down into: ‘anti’ (against) and ‘biotic’ (life). Antibiotics act to inhibit the growth of, or kill, microorganisms, preventing their spread and multiplication. The first – and still most common – antibiotics come from fungi (e.g., penicillin) and specifically fight bacteria. Before the development of antibiotics for widespread use, about 70 years ago, there was a high mortality rate from bacterial infections, such as tuberculosis, pneumonia, and sexually transmitted contagions.

Today, many forms of antibiotics exist to treat several different types of infections, including parasitic infections and some fungal infections. However, antibiotics do not work on viruses because viruses are not living organisms and so are ‘not alive’. Unlike living organisms with their own cells, viruses are segments of DNA (or RNA) that inject themselves into living cells, forcing those cells to do the work of reproducing more of the viral DNA.

This is why your physician will not prescribe an antibiotic for the common cold or flu. When we are sick, we often don’t know the full nature of the infection that is attacking our bodies. We just feel bad. This can be confusing because, for example, while a cold virus attacks our body, our immune system is working extra hard and we become vulnerable to developing other types of infections, such as pneumonia or strep throat, which are bacterial infections and usually treated with antibiotics.


None of this covers the new need for antibiotics, driven by industrialisation, the rise of disease due to poor santisation and squalid housing and living conditions caused by the industrial revolution as people moved towards cities.


From conversations with medical professionals: Antibiotic “misuse” is one of the most frustrating things in the field. They’re taught about antibiotic resistance in school, but then contribute to the problem by overprescribing it. The y describe the circumstances that patients (and parents) just want “a pill” to solve “a problem”, and that while the doctors know that it’s a viral infection, they still prescribe the antibiotics to placate the patient/parent. Further compounding the problem.

They’d be better just prescribing placebos or “drink some ginger garlic tea and rest”


I do not understand why there is a huge gap between scientific knowledge and physicians.

I had a problem with an allergic reaction to an antibiotic. This resulted in me actually paying attention to drug labels, side effects and what a drug is being prescribed for. It has quite literally ruined my trust in doctors.

Last year I had stomach pain, I thought it was appendix. So, I went to an urgent care because my physician could not see me. They had access to my medical records. Quickly, I receive a diagnosis of "Diverticulitis". 2 minutes later I'm given a prescription for Cipro, which I'm deadly allergic to. New guidelines suggest not using antibiotics in uncomplicated diverticulitis. I didn't take the meds, and I'm pretty sure I just pulled an abdomen muscle as it healed over the next few weeks.

I have many stories from sports injuries and doctors offering steroid injections as first line treatment, which is no longer recommended.

NSAIDs are also not recommended for tendon injuries and it is the first thing the doctor will offer.

I don't get it. The information is easily available. Saying I read a study or a updated recommendation gets most doctors visibly upset. Not sure if it is the long working hours and trying to move as many patients as possible or just lack of giving a fuck.


Warning: anecdotal evidence from a limited perspective.

I did a biochem undergrad and was surrounded by premed students. Every single one of them was a North Face-wearing, click-y, "there to get the grade" student. They didn't display the same kind of awe for the amazing biological processes we were learning about, and they certainly didn't put in any legwork into undergrad research projects. They weren't nerds. They wanted a job with prestige and money. Several of them were bullies that talked bad about us and were not fun to be around.

I spent my time thinking about human regenerative cloning, transfecting biochemical synthesis pathways into things, the metabolome, connectome, etc. They used flash cards and socialized and would quickly change the subject when talking about biology topics. The material didn't matter one bit to them.

Complex things were gamed even more. They spent their time memorizing o-chem reactions rather than following the electrons.

My experience led me to believe that there are doctors that are only after the title and wage. They're not domain material geeks like us. I just question how many are actually like that, because my school was loaded to the brim with these people.


That's funny because something similar happened to a friend of mine. He was the only biochemist in a class that was mandatory for med students. It was about drugs and their (side) effects. The professor was so happy that there was at least one student in the room who could answer his (mostly rhetoric) "why" questions, while the other students were just memorizing.


"like us". It seems like the developer field has its share of Brogrammers and other non-traditionally nerdy types. Speaking as a super-nerdy science geek, it's probably not all bad that the field has widened - along with the bro's you get more women, non-compsci, and people-of-color entering the field, if some of the gate-keeping is relaxed.

There are MD/PhD doctors out there at the cutting edge, but most docs are more like PC repair techs - swap things out until the problem goes away, have a basic understanding of the underlying tech. You don't have to be a chip designer to swap a motherboard, or follow the electrons to prescribe some meds :-)


  > My experience led me to believe that there are doctors that are only after the
  > title and wage. They're not domain material geeks like us. I just question how
  > many are actually like that, because my school was loaded to the brim with these people.
There's a quick way to tell if a field is staffed _mostly_ by enthusiasts or mostly by money. Does the field have an active after-work topic community?

There exist active lawyer forums, and the things they discuss might as well be philosophy for the depth of analysis they invest. Software forums by the ton. Nurses seem to have active forums, though I haven't really looked at them. Vehicle mechanics, musicians, agriculture, teachers, pilots, scientists, authors, truck drivers, engineers, even construction. I could go on.

Which major top-dollar professions do not seem to be represented? Doctors, office administration, bankers. These are professions that seem to have very few enthusiasts working in the field. I'm sure they exist, but they are rare.

I should go tell my physician how much I appreciate her. I have a good one.


Exactly what I also wrote. The only people who are really good at any complex topic are huge geeks with some level of obsession for it. I've met plenty of programmers, mathematicians and even some finance people (those people work in trading) who are like that, but never a doctor.


I've met internists who are like this. Encyclopedic knowledge of their field, excited about theory, obviously spending a lot more time on literature than they're strictly required to. It kind of makes sense that the "true nerds" would end up in these jobs, because specialized internists spend tons of extra time in training but make less money than "procedural" specialties (surgeons, mostly).

The best family doctors I've met aren't mega-nerds but at least seem to genuinely care about helping people.


How many of them made it? Of the people I knew in college that wanted to go to medical school afterwords, like 1/8 of them actually got in.

(I went to a good school, these were intelligent people)


Ditto. While I'm sure they get patients who read random stuff on the internet, its frustrating that I can often get better information searching the internet with a basic understanding of how to determine the validity and how damn often thats better than my doctors recommendation and understanding and how often it changes the treatment path that would have been taken.

You absolutely need to be your own advocate because most doctors just follow a playbook and/or don't have time to think deeply on your issue, and/or don't spend time keeping their knowledge up to date.


To add another anecdote from the perspective of living in two countries - the recommendations we get from doctors in each country are often polar opposites of each other. Drugs available over the counter in one country are outlawed in the other, and vice versa. Information from a trustworthy source in one language is called pseudoscience in the other, and vice versa. Meanwhile, the health outcomes do not seem to be significantly different in either place. I am less and less convinced by anything my doctor says, in any language.


At the population level, outcomes are driven mostly by public health measures (clean water, food safety, vaccination) and cultural factors (obesity, substance abuse). Individual healthcare interventions barely move the needle.


I don't have the citation handy but the Institute of Medicine researched this and found it takes about 17 years in average to get all physicians to adopt new clinical practice guidelines. For physicians with a wide scope of practice it's just tough to keep up with all the chances. There might be some opportunities to use technology in clinical decision support systems that warn about potentially inappropriate treatments, but those have to be handled carefully so as to not slow down patient care unnecessarily.


Possible explanation: People who become physicians do so for wrong reasons. Medicine is highly paid, high status field and thus attracts people who are reasonably smart and just want to have a good life, but are, in the end, not very internally motivated to keep studying their field. Better system would select for people who are more geeky and like to read the new antibiotic studies for fun, much like many developers do stuff like write their own compilers and file systems for fun.


Have you ever talked to real physicians? Except for a few small specialties the pay isn't that great once you factor in educational expenses, unpaid overtime, and liability insurance. Very few are really in it primarily for the money.

We already have a shortage of primary care physicians. Imposing additional selection criteria based on some arbitrary, subjective measure of geekiness would be completely stupid and counterproductive.


Expected lifetime earnings for a typical doctor are ~$7M compared to ~$1.4M for the median person. The pay might not be "that great" by your standards but it's still 4x more than the typical person earns, even taking into account ~$500k of education costs. A typical lawyer makes only ~$5M and has similarly expensive education and a demanding work schedule.

Software engineers only started earning that kind of money in the last decade or so. When today's new doctors were starting off on their education path ten years ago, doctors probably still earned twice as much as even top software engineers.

Medicine is also prestigious in a way that few other careers are. People take notice when you say you're a doctor, and a lot of people enjoy that feeling. A huge number of parents pressure their kids into pursuing medicine, having your kid become a doctor is a surefire way to win the status game among your friends.

I personally know quite a few doctors. I'd say for most of them that desire to help people and desire for personal status were both motivating factors in their career choice.


But they don't know this before starting, which makes things worse. People are even less motivated after they discover this, especially if they started this career for the money.


I know people who got into the medical field because the like "Grey's Anatomy". Incompetence and lack of internal motivation is everywhere. I think most people are just not good at their job.


Urgent care doctors in particular are basically glorified pharmacists. I will never go to an urgent care unless I know what it is and how to fix it, and I just need their signature.

If you need real help, go to an emergency room or wait for a specialist.


It isn’t so much a knowledge gap as misalignment between patient and doctor interest: there is pretty much zero incentive for doctors to follow a non pharmacological path, limited incentive for them to follow a more difficult pharmacological path, and low to no cost to them for following that easiest pharmacological path.

Doctors are highly trained technicians who are well rewarded for processing patients quickly and are well protected (insured) against the inevitable occasional error, assuming such thing can be a) detected and b) proved.

We are better protected from our lawyers and bankers than we are from our doctors.


It really astonished me how doctors still continue to suggest NSAIDs and RICE for muscle or tendon injuries. I would understand if doctors didn’t adopt best practice for uncommon ailments, but muscle / tendon issues are so common…


It's about money and they just want to get rid of you, because they are understaffed, overworked and not happy people.


> I do not understand why there is a huge gap between scientific knowledge and physicians.

Why do you assume physicians are making their treatment decision based on gaps in their scientific knowledge or incompetence?

I am not a physician, but a major factor you are completely ignoring is liability. By prescribing/treating aggressively they know they are guaranteeing negative side effects that may be unnecessary. But they need to weigh that against chance of a terrible outcome for the patient & potentially loosing their livelihood.


I don't think you read the complete post.

Let's take fluoroquinolones for example. It is an extremely dangerous antibiotic, no longer recommended as a first line treatment for simple infection. Yet, patients are being prescribed it for SUSPECTED unconfirmed infections. This screams either incompetent physician or lack of familiarity with current scientific knowledge/new guidelines.


> Let's take fluoroquinolones for example. It is an extremely dangerous antibiotic, no longer recommended as a first line treatment for simple infection. Yet, patients are being prescribed it for SUSPECTED unconfirmed infections. This screams either incompetent physician or lack of familiarity with current scientific knowledge/new guidelines.

Which is the same example you gave in your first post...

> Yet, patients are being prescribed it for SUSPECTED unconfirmed infections.

AFAIK bacterial infections are in-practice often only suspected not confirmed before prescribing anti-biotics so why emphasize this?

Like I said I think you are ignoring other incentives (Malpractice Risk, Bias for action etc.) at play that cause a Physician to look at the same situation and come to a more aggressive treatment plan than your armchair diagnosis.


>AFAIK bacterial infections are in-practice often only suspected not confirmed before prescribing anti-biotics so why emphasize this?

It does happen but is a HUGE problem in medicine. This doesn't mean this is the CORRECT procedure and exactly what I am talking about. Infection should be confirmed and correct antibiotic used. Plus, not all infections require antibiotics.

>Like I said I think you are ignoring other incentives (Malpractice Risk, Bias for action etc.) at play that cause a Physician to look at the same situation and come to a more aggressive treatment plan than your armchair diagnosis.

By not following guidelines and prescribing wrong medication or when medication does not help a specific problem the physician is a lot more likely to be sued if patient suffers from side effects.


This is a huge problem, and something really ought to be done about it. I'm not sure what that would look like from a top-down, structural or regulatory perspective (loosen regulations and make it easier to become a doctor so that we have more doctors with more time?), but I have some bottom-up, individual-level ideas that I described in a comment on another post[1]:

---

> We briefly discussed my anxiety, but his immediate solution was the anti-anxiety drug. I made it clear that I was worried about the procedure and wanted to know more details about it. He didn’t want to explain the procedure beyond “we’ll inject medication that will help preserve your vision”, and he avoided answering repeated questions. Maybe he tried to shield me from the details and not confirm my worst fears.

Based on stories I've heard from emotionally immature doctor friends and my own experience being a little more confrontational with my doctors, he most likely didn't know the answers to your questions and was too proud to say, "I don't know."

It seems many forget that, at the end of the day, doctors are people, too, with just as many flaws and emotions as the rest of us. It's unfortunate that this affects quality of care, but it's a fact of life in every industry.

The best thing you can do for yourself in such a situation is to prepare yourself before appointments and remember the humanity of doctors during appointments. If your doctor is being dodgy about answering questions, let them know that it's okay if they don't know and that you won't think anything less of them for it. If it's an urgent matter, suggest looking it up together so that your doctor can provide context for whatever research you manage to find.

A doctor is like a contractor you've hired to inspect and maintain your body. As with any contractor, if you want them to do a good job, you have to work with them, as a team.

---

And, as a child comment pointed out, if you really don't like your contractor, you can always fire them and find a new one, and in fact, you should. Don't reward people for bad behavior, vote with your wallet, etc. etc.

[0] https://news.ycombinator.com/item?id=29109114


I don't buy that the primary issue is with human antibiotic use.

Doctors have become increasingly stingy with antibiotics, sometimes at the expense of human well-being -- meanwhile 80% of antibiotics are used in livestock production.

We could reduce the need for antibiotics in livestock if we treated animals better. Giving animals a bit of breathing room and fresh air would reduce the need to jack them up on antibiotics from day one.

Reducing use in humans seems like banning straws to take on plastic waste -- a feel good policy that won't actually fix much.


I have to wonder, though, if it's human prescribed antibiotics that source these super-bugs.

It's pretty common practice in the cattle industry, for example, to just pump cows with antibiotics because studies have shown cows constantly on antibiotics grow fatter than cows not on antibiotics. (Likely, because they don't ever really get sick). [1]

That makes me wonder how many of our super bugs have origins in the livestock industries where common practice is literally a recipe to bread superbugs.

[1] https://www.cidrap.umn.edu/news-perspective/2020/06/report-s...


It's been funny working at the intersection of human and animal health. The medical types all want to blame agriculture. The agriculture types all respond that they're not using major frontline human antibiotics (outside some stuff for companion animals).

It's sort of a complex mix - there's a lot of bulk use in agriculture, but the drug-microorganism pairings in human medicine are somewhat more acute.


This is one of the contentious points in trade between the USA and the EU: The EU does not allow preventive antibiotic use, but the USA does. Same for growth hormones. As a result, USA meat can not be imported in the EU. USA claims this is foul play, protectionism, against WTO rules.

Now the EU does allow curative antibiotic usage on animals, so I wonder if this is actually such a big difference. If a vet prescribes antibiotics for the slightest reason, there might not be much changed in reality.


This is certainly a problem when banning antibiotics for growth promotion, but allowing the prophylactic use of antibiotics.

Any animal in the type of farm looking for growth promotion is at risk for a bacterial infection basically all the time.


Isn’t this paper actually debunking that argument (That overuse of antibiotics has increased antibiotic resistance)? The paper says that resistance didn’t diminish when antibiotic use was decreased. It seems that our common understanding of how resistance develops was incorrect, at least partially.


If there is selective pressure to increase resistance, resistance increases over time.

If there is not selective pressure to increase resistance... nothing. There is no pressure to change anything relating to resistance. It could increase. It could decrease. It could stay the same. There is no reason to expect anything in particular about it.


Of course, but the US fee-for-service model is aligned elsewhere. I think a lot of them think that as long as they are not prescribing a z-pack every month, it won't be that big of a deal. Also, customer acquisition is hard. Patients will just find another primary or go to an urgent care and get the meds there. For primary care, being seen as "not helpful" won't just lose one patient, but a whole household of them. As you quote above, people want a quick fix. The person consuming 3000 calories of carbs per day wants a magic pill to fix their type 2 diabetes without them having to make any changes. I don't envy them.


SGLT2 inhibitors pretty much are magic pills for type 2 diabetes.

https://www.fda.gov/drugs/postmarket-drug-safety-information...

But of course it's better to prevent the condition in the first place.


Wait until people find out the side effects, then you'll get another thread exactly like this one but about SGLT2 inhibitors instead of antibiotics


Another very promising treatment for type 2 is DMR. We need to do a lot more research on the duodenum as it is clear it is a major linchpin in type 2.

[https://gut.bmj.com/content/69/2/295]


Autophagy is the real silver bullet for T2DM treatment but you won't get that from a pill especially if you continue to ingest sugar.


There was talk to the placebos on SBM at one point, the gist of it being that it would be far worse for them to do so for a few reasons. It erodes trust is the big point. But, I assume, there would be issues with informed consent too. How does one prescribe a placebo where the user can lookup the drug by name online.

Not a medical professional, but I think the issue comes down to doctors saying no as a group and being ok if they shop another doctor. If enough do that, the issue goes away.


It seems odd to me that doctors are even allowed to prescribe antibiotics when they know they aren't necessary. Why shouldn't that be grounds for disciplinary action?


That's one of the interesting experiences when moving to Sweden. One is highly unlikely to be prescribed antibiotics here, and one gets prescribed very "old" antibiotics, that my partner who was trained in France said are hardly used anymore in France due to resistances. When she started working as a GP here she found out that it's very hard for doctors to prescribe antibiotics, i.e. the conditions under which doctors are allowed to prescribe them are very strict.

There's a lot of things that are frustrating about the medical system here, but the restrictions on antibiotics is one of the very good things.


Sounds sensible, but I imagine it won't do much good if it's just Sweden doing it.


You're right it won't do much good, but it is nice to see a country take a principled stand and actually practice what they preach and be the change they want to see.


Why prescribe it if we know it is viral? First, the doctor should determine whether or not it is viral or bacterial. If it turns out that it is viral, then DO NOT PRESCRIBE ANTIBIOTICS. Is it because of placebo? Because if so, the costs are too high. Tell them to take zinc or whatever for a week.


Well, that’s not covered by my health plan!


Why are Fluoroquinolone Antibiotics (FQs) such as Cipro, Levaquin etc. even still on the market, from the many life long devastating side effects they cause many?

The FDA itself has said that this class of Antibiotics should be reserved until ALL other options have been exhausted. Yet doctors are giving this crap out like candy. Usually for things that they don't even work for such as UTIs see FDA July 26 2016:

"Limits use for acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis and uncomplicated urinary tract infections." See link below.

Because for those items they don't work any better than a placebo, as the FDA itself documented in this 617 page report:

https://web.archive.org/web/20170113234645/http://www.fda.go...

On page 17 of that report they even give a name to the problem these antibiotics cause:

'"fluoroqunolone-associated disability" (FQAD)'.

I have gathers all of the FDA warnings, and a few from the EU that say don't use them at all, about FQs at my late wife's website:

https://www.kpaddock.com/fq

In large part she is my late wife because of Levaquin causing her systemic tendentious. After several years she killed herself to stop the pain from that and CSF Leaks. For that whole saga see the documentary Pain Warriors that is free to watch on Amazon Prime and TubiTV:

https://www.kpaddock.com/pw

For me because of all of that it comes down to don't trust Big Pharam and the Medical Establishment with your health. Study EVERYTHING and make an informed decision before taking anything a doctor offers you.

Ask them "Is my problem being caused by a pill deficiency?" and watch their stunned looks...

On a possible upside there is some work coming around on using Phages as a type of antibiotic. The founder of this company experienced her own antibiotic resistant infection. [Full disclosure I have communicated with her about the above FQ issues, I receive nothing from them.]

https://www.felixbt.com/new-page


What's interesting is that the same principle doesn't seem to apply for viral infections.

The smallpox vaccine is just as effective today as it was a couple decades ago.

Then again the flu is constantly mutating so maybe it's just contingent on the type of disease.


Depends on which virus. Flu shots have to be changed every year, but measles shots appear to give lifetime immunity.


Flu doesn't evolve to resist each vaccine, it's just a different strain becoming prevalent each year. I'm not sure what the mechanism behind that is, but it was happening before the flu vaccine existed.


Definitely, there is selection pressure for new strains so that it can reinfect people which have immunity from last year.

The flu virus is really good in mutating because its genome is made 7 or 8 parts which can be exchanged between strains. Most other viruses don't have these segmented genomes and are somehow stuck in a local optimum, so they can't evade the immunity so easily.


Is there much difference conceptually between a virus mutating in a body and then finding ready hosts amongst the vaccinated if there is a large vaccinated population and a bacteria that has a resistance to an antibiotic spreading in a host that is receiving that antibiotic?

Sorry for probably not using the right terminology here but they seem closely related to me.


Antibiotic resistance is usually on plazmids which can be exchanged between different bacteria (often even between different bacterial species). So only one bacteria needs to find the right gene and it starts spreading.

Viruses have really small genomes and simply adding a gene for bypassing immunity does not work. It would need to restructure it's surface proteins so that the immune cells can't recognize it anymore, but this restructure often breaks the virus.

Also there is the thing that antibiotics are present at low concentrations everywhere which makes small but constant pressure for the resistance genes.

> On a larger scale, since 1940, antibiotics have become an omnipresent pollutant in environments of all types (55). Even in places largely untouched by humans, we can find antibiotic compounds and, with them, ARGs (56–59). In recent years, we have learned that even low levels of antibiotic pollution select for high levels of resistance (60–62). Additionally, regardless of the biome or their ability to clear pollutants, humanity’s worldwide industrial-level use of antibiotics has resulted in a steady stream of antibiotics into the environment, without ever allowing natural systems to return to baseline levels (63).

Immunity does not come in this constant small pressure. You either have it and then the virus is dead quickly, so it does not have much time for finding mutations. Or you don't have it, so there is no pressure for the mutations.




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