[HN Gopher] Why do antibiotics exist?
       ___________________________________________________________________
        
       Why do antibiotics exist?
        
       Author : maxerickson
       Score  : 56 points
       Date   : 2021-12-08 19:13 UTC (3 hours ago)
        
 (HTM) web link (journals.asm.org)
 (TXT) w3m dump (journals.asm.org)
        
       | DantesKite wrote:
       | 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.
        
         | not2b wrote:
         | Depends on which virus. Flu shots have to be changed every
         | year, but measles shots appear to give lifetime immunity.
        
           | roywiggins wrote:
           | 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.
        
             | bink wrote:
             | 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.
        
       | Gunax wrote:
       | 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.
        
         | tshaddox wrote:
         | 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.
        
         | Fomite wrote:
         | It definitely is - both in the developed and developing world
         | there is a staggering amount of overuse of antibiotics.
        
           | xmprt wrote:
           | 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.
        
             | droopyEyelids wrote:
             | 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.
        
               | Fomite wrote:
               | It's more of a "yes and..." problem. There's also a
               | sanitation aspect to things.
        
         | jurassic wrote:
         | 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:
        
           | vkk8 wrote:
           | 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).
        
             | nradov wrote:
             | The FDA has already been working to reduce antibiotic use
             | in agriculture.
             | 
             | https://www.fda.gov/animal-veterinary/safety-
             | health/antimicr...
        
             | culi wrote:
             | I wouldn't call it low-hanging fruit considering just how
             | dependent large-scale animal agriculture is dependent on
             | antibiotics
        
             | mdavis6890 wrote:
             | 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.
        
       | throwoutway wrote:
       | 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"
        
         | cogman10 wrote:
         | 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...
        
           | Fomite wrote:
           | 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.
        
           | hyperman1 wrote:
           | 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.
        
             | Fomite wrote:
             | 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.
        
         | fennecfoxen wrote:
         | Well, that's not covered by my health plan!
        
         | snarf21 wrote:
         | 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.
        
           | nradov wrote:
           | 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.
        
         | MaxBarraclough wrote:
         | 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?
        
           | [deleted]
        
           | cycomanic wrote:
           | 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.
        
             | MaxBarraclough wrote:
             | Sounds sensible, but I imagine it won't do much good if
             | it's just Sweden doing it.
        
         | beached_whale wrote:
         | 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.
        
         | cortesoft wrote:
         | 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.
        
           | commiefornian wrote:
           | 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.
        
         | avgDev wrote:
         | 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.
        
           | bserge wrote:
           | It's both. On the one hand, I hate the fuckers who don't give
           | a shit, I've met way too many of them.
           | 
           | On the other hand, too many times they are overworked and/or
           | underpaid. At some point anyone will stop giving a fuck.
           | 
           | Surgeons, dentists, EMTs deserve respect though. Yeah they
           | fuck up, but nowhere near as often or bad as those
           | responsible for gatekeeping useful medicine.
        
           | peakaboo wrote:
           | It's about money and they just want to get rid of you,
           | because they are understaffed, overworked and not happy
           | people.
        
           | nradov wrote:
           | 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.
        
           | PeterWhittaker wrote:
           | 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.
        
           | echelon wrote:
           | 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.
        
             | tralarpa wrote:
             | 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.
        
             | ianmcgowan wrote:
             | "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 :-)
        
             | vkk8 wrote:
             | 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.
        
           | jonshariat wrote:
           | 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.
        
           | cosmojg wrote:
           | 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
        
           | vkk8 wrote:
           | 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.
        
             | nradov wrote:
             | 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.
        
             | jebronie wrote:
             | 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.
        
           | getoj wrote:
           | 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.
        
             | nradov wrote:
             | 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.
        
           | darkerside wrote:
           | 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.
        
         | nostromo wrote:
         | 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.
        
       | sattoshi wrote:
       | > 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.
        
         | rudyfink wrote:
         | 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.
        
         | christkv wrote:
         | 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.
        
         | Fomite wrote:
         | 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.
        
           | jessriedel wrote:
           | 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.
        
             | Fomite wrote:
             | Yeah, but this was _very much_ a just so story.
        
         | wonnage wrote:
         | 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.
        
           | brazzy wrote:
           | 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.
        
       | User23 wrote:
       | 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.
        
       | alan-crowe wrote:
       | 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.
        
       | mrtweetyhack wrote:
       | for the same reason biotics exists
        
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