Why do antibiotics exist?
journals.asm.org
journals.asm.org
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.
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.
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.
I guess there is no money in requalifying an out of patent antibiotic.
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.
Are you using "just so" as a synonym for "suspiciously convenient"? That's not what it means.
"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.
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 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'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.
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.
https://www.fda.gov/animal-veterinary/safety-health/antimicr...
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.
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.
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.
There's not really any mystery why that helps them grow of course.
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.
Flu and coronaviridae.
Shit, thoughtcrime. Hope I don't get vanned.
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?
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.
They’d be better just prescribing placebos or “drink some ginger garlic tea and rest”
https://www.fda.gov/drugs/postmarket-drug-safety-information...
But of course it's better to prevent the condition in the first place.
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.
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.
The best family doctors I've met aren't mega-nerds but at least seem to genuinely care about helping people.
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 :-)
(I went to a good school, these were intelligent people)
> 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 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.
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.
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.
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.
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> 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.
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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.
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.
If you need real help, go to an emergency room or wait for a specialist.
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.
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.
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.
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'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...
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.
Any animal in the type of farm looking for growth promotion is at risk for a bacterial infection basically all the time.
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.
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.
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.
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.
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:
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:
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.]
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.
Sorry for probably not using the right terminology here but they seem closely related to me.
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.
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.