Antibiotic resistance: The grim prospect | Hacker News Reader

Antibiotic resistance: The grim prospect

economist.com

105 pointsknown66 comments

Medical professions risk losing a patient or being sued if hey misdiagnose a condition, so the understandable reaction is to throw antibiotics at the problem rather than waiting for test results to come-back to determine whether a specific course of care is appropriate.

The good news is that some test times are decreasing dramatically ... from days to minutes in many cases:

http://nanologix.com/test_results.html

  * tuberculosis from 21+ days to 1.5 hours.

  * e.coli from 18 - 24 hours to 30 minutes

  * salmonella from 24 hours to 30 minutes

  * group b streptococcus from 48 - 72 hours to under an hour

My hope is that faster results leads to fewer unnecessary prescriptions being administered, and better overall care for the patients.

> Medical professions risk losing a patient or being sued if hey misdiagnose a condition, so the understandable reaction is to throw antibiotics at the problem rather than waiting for test results to come-back to determine whether a specific course of care is appropriate.

As a pharmacist, my experience says otherwise. I think the following are the main reasons for bacterial resistance:

a) Patient doesn't respect doctor's/pharmacist's guidelines. He feels much better after day 3, so he stops his class X ATB in day 4 instead of day 7. If bacteria survives, might very well be class X ATB-resistant.

b) Patient has a relative who when was feeling sick took ATB XYZ and got better. The main reason for this is poverty: A visit to the doctor might cost 25-120 EUR.

c) Hospitals. MRSA became "MR" in hospitals, where bacteria conjugation takes place.

That said, at some in point, we should expect bacterial organisms to evolve some kind of resistance. That's how evolution works.

Regarding (a) - do you know that I've never been told why I need to finish my antibiotics? For some reason (arrogance?) doctors don't explain their reasoning in many cases (I live in Canada FWIW.)

If I was told "hey, you need to finish your antibiotics or you'll risk becoming immune to them, potentially putting yourself or your family, colleagues, or friends at risk" I don't think even the dumbest person would ignore that warning. Then they could even explain WHY that is, if the patient was curious.

Instead, here in Canada, you say you're sick, the doctor will likely immediately perscribe antibiotics, then shuffle you out the door in less than 5 minutes.

This is a more general problem. Warning labels on toothpaste and such generally include the phrase "SERIOUS INJURY OR DEATH MAY RESULT" if they really mean something's dangerous. Medications don't seem to do the same thing, so you can't tell if they're worried about you irritating your stomach or ending the human race.

In fact, I have a medication right in front of me that has a little label on it that says "Take or use exactly as directed. Do not discontinue or skip doses unless directed by your doctor."

That's all it says about it on the bottle. Doesn't explain why. Doesn't say how serious it is. Doesn't even use an exclamation point. My first thought is, well, I've had lots of medications before that came with labels like that, and what they meant was, "You might get a little dizzy for a day or so if you stop too fast." Not this one, it turns out. Three paragraphs into the fine print on the literature that came with it, it says, "Some people who have suddenly stopped taking similar drugs have had . . . heart attacks." Oh.

That really seems like it ought to be worth a "SERIOUS INJURY OR DEATH MAY RESULT".

Not only in Canada, it's like that in every country I've seen a doctor.

As for the 'why'... You'd be surprised on how difficult is to get an answer like that from any doctor. My suspicion[0] is that they simply don't know anymore: It's something they learnt in college, but after a few years of dealing with symptoms and prescribing treatments, they forget about the why.

Don't get me wrong, I kind of understand it. On one hand I've found that most people don't care about the 'what's or 'why's of medicine. They go to the doctor and either take the treatment they prescribe or not. I think the people that want to know the 'why' are a minority and doctor's time is valuable, so they end up processing people as fast as they can.

On the other, medicine is a vast field and they need to keep up to date with the latest developments, so I can see how they can start to forget seemingly superfluous pieces of information when faced with all the new info they have to absorb.

[0] From personal observation, so I can (I hope) to be mistaken.

> My suspicion [from personal observation] is that they simply don't know anymore: It's something they learnt in college, but after a few years of dealing with symptoms and prescribing treatments, they forget about the why.

If your doctor actually doesn't know why it's necessary to take the full course of antibiotics (antibiotic resistance), please get a new doctor. Seriously. (And report the old one, since he/she should not be practicing).

Of course, if the problem is simply that you can't get a layperson-intelligible answer from them, or get enough time with them for them to explain it to you, or if they're willing to explain it to you, but only if you ask... that's another story, and much more commonplace.

The sad truth is, even for the most compassionate, attentive, dedicated doctor - the one who would always go the extra mile to provide you with the best care imaginable - over the years, it's become increasingly difficult (read: next-to-impossible) to dedicate that extra time to the patient unless they really press for it. Insurance reimbursements have been cut to the point where the only way most physicians can stay afloat is to make their practice a volume game[0]. As the patient, you're not actually the paying customer (the insurer is), and the insurer doesn't care if the doctor takes an extra five minutes to talk about bacterial resistance and evolution. They'll reimburse him/her the same amount either way[1].

The exception to this is high-end, self-paying practices (think 'concierge medicine'). Unsurprisingly, those tend to have the best service (of course, you pay heavily for this).

[0] Or to go bankrupt, and sell to a hospital/practice group. Which is subject to the same pressure to generate volume, except the hospital cares a lot less about you, the patient, on an emotional level than a private practitioner does.

[1] In fact, in the worst case, the provider is getting reimbursed exactly $0 for providing you this care, because you're on a capitated plan. Under captitation, the provider (usually a hospital) gets a fixed, annual amount per patient that they are responsible for, and that's all the payment they ever get. The idea there is that it discourages unnecessary care - which is true, but it also disincentivizes necessary care as well. And spending an extra 5 minutes to educate the patient in a way that may have an impact on broader public health, but is unlikely to affect their own actual care in any measurable way? They don't have time for that, and they're certainly not getting paid for it.

As I said in other comment, the antibiotics one is a very simple case, but I've had plenty of other examples.

As to report the doctor... To whom? Do you know how difficult it is to prove almost any kind of malpractice? I've had a doctor insist that I had a sprained wrist when it was a broken radius (as another doctor and a simple x-ray proved). Another said that the cramps I was having were from an unborn brother (ahem). My wife was told in the hospital that she wasn't having an allergic reaction to antibiotics because she had had them before (surprise, antihistamines helped and further tests detected she's allergic to penicilin).

Of course, nothing gets written and doctors are very quick to cover each other. So how do you report these?

As for the doctors not being able to dedicate extra time to patients, I totally agree and indeed mention it in my first message.

> As for the 'why'... You'd be surprised on how difficult is to get an answer like that from any doctor. My suspicion[0] is that they simply don't know anymore: It's something they learnt in college, but after a few years of dealing with symptoms and prescribing treatments, they forget about the why.

The reason why is very simple Biology 101 level material. It's so fundamental that it makes your last statement incredibly comical. Forgetting this is like forgetting that your computer is powered by electricity.

You are right, the antibiotics one is pretty simple, I ran with it because I didn't want to get into personal details.

Let's put a simple one from my experience: No doctor has been able to tell me what the bilirubin is. They go on to tell possible causes, and what it means to have a high value and so on.. but after hours with them, no one could tell me what it is.

The closer I could get was for one of them to tell me that its secreted by the liver (close, but no cigar). The first paragraph in wikipedia explains it perfectly.

I know that my computer is powered by electricity. I know most of the ways to produce said electricity, but I've forgot the details of an hydroelectric plant even though I studied it in college; it's not part of my daily life.

I also know that power lines use alternate current and computers use direct current, but I've forgot the details of the AC/DC converter. Even though I was able to design one from scratch in university.

I also studied the internals of microprocessors up until the pentium, how they were designed and manufactured, but nowadays all I remember, vaguely, is the x86 assembler.

Do you remember every single detail you studied in college? Do you know how to calculate the root of a number by hand? I don't. Not anymore.

I had also never heard an explanation before. I'd like to think I would inquire if it came up (haven't needed antibiotics since I was a kid), but many people aren't inquisitive.

I had a similar lightbulb moment when I heard why you shouldn't slouch, even though it can be comfortable: the intervertebral discs in your spine are poorly innervated[1], so you don't feel the damage you are causing until it is severe.

1 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2913007/

> Regarding (a) - do you know that I've never been told why I need to finish my antibiotics?

Drug therapies have specific regimens that need to be respected in order to ensure the highest degree of success. An average regimen for penicillins (penicillin-derivatives) is 7 days because that's how many days it takes for the ATB to kill the bacterial infection.

Now all the above is the N-th level of abstraction. If you really want to know what's on you need to start doing evaluations. You need data like from the patient like:

- Age - Kg - Health state (liver, nephrons, stomach, allergies, etc.) - History the specific class of ATBs (how did your body and the infection react to this class of ATB in the past?) - Other medication (are there interactions with other drugs a patient might be taking?) - Food (e.g. you shouldn't eat St. John's Wort while on drugs, because it's a CYP3A4 inducer and so on and so forth...) - etc.

And it goes further down the rabbit hole depending on the case. So, I of course prefer doctors who are big on explaining what's happening, but I understand those who don't.

The thing is that once the doctor starts talking ,you will probably start asking why, especially if you're an engineer who wants to put everything into context. At some point you'll just won't be able to understand - which means he'll have to make silly analogies, even more explanation, etc. Add to that you might have been his 20th patient that day and you get the point. On the other hand, if you pay for it, you should be able to get a doctor which gives you the appropriate amount of care/explanations.

For some reason (arrogance?) doctors don't explain their reasoning in many cases

In this case it might be as simple as "I don't have time to argue with the patient about evolutionary biology." But that's probably a bigger issue in the US than in Canada.

This ignores livestock which is both a huge vector for resistance and part of the food chain. It's not like this is new, Sulfa drugs worked really well for a short period of time before penicillin and are now somewhat useful.

This. FDA estimated 80% of antibiotics are used for livestock. Cite: https://www.govtrack.us/congress/bills/112/hr965/text

> Patient doesn't respect doctor's/pharmacist's guidelines.

This is not at all restricted to antibiotics. I still treasure the memory of listening to a cardiologist ream out a patient over the phone on either Christmas or New Year's Eve (I was waiting for him to leave so I could take the servers down). Said patient hadn't been seen in the office in 6+ months, had gotten things prescribed by other docs in the interim, and had decided to stop taking some of what had been prescribed effectively self-medicating.

The basic message being passed to him was "You're an idiot, you're going to die, if you have problems over this long holiday weekend call the doc who saw you most recently or get to the ER, did I mention idiocy and death?, we haven't seen you in months and didn't prescribe what you're doing and are not responsible for your stupidity, I'm documenting this in your chart."

IIRC, in this case the patient had kept taking a diuretic that had a side effect of potassium elimination but had decided to stop taking the potassium supplements needed to counter that.

How much of bacterial resistance is from patient's not finishing a dose of medicine and how much is from increased use of antibiotics as a whole (in the farm system, in people, etc)?

Researchers are not totally clear on this. One particularly dangers spread is counterfeit medications that don't reach the MIC required to kill the Bacteria, and instead create in people exactly the same situation that biologist use to grown AMR bacteria in the lab.

"That's how evolution works" - good point, and also probably a promising area to look for new ideas.

e.g. bacteriophages

Fight (blind) evolution with (directed) evolution. In the long run, it's the only strategy that works.

I understand there is also a

d) feeding farm animals antibiotics to promote growth/weight gain.

Are the false positive rates comparable between the older slow tests and the new fast ones?

Depends very much on the test. The study I did for rapid influenza tests showed that their accuracy was pretty bad. Very sensitive, not at all specific.

And faster identification of AMR strains in order to choose first line AB's appropriately.

Chemical antibiotics are currently the best and most developed tool we have for bacterial infection, but other options are being explored, including defensins[1,2,3] (antimicrobial peptides) and—as mentioned in the article—phage therapy[4,5,6,7] (viruses that infect and replicate within a bacterium). Like many of our current antibiotics, they have their origins in nature. As therapeutics, they're far off, and would have to be characterized and go through the usual clinical trial process to be evaluated for efficacy and safety. Specificity is an issue for phages, and delivery is a challenges for both. One novel application is a defensin-based chewing gum being developed by the US military to combat the bacteria responsible for dental plaque[8,9].

1. http://www.nature.com/nri/journal/v3/n9/full/nri1180.html

2. https://en.wikipedia.org/wiki/Defensin

3. http://onlinelibrary.wiley.com/doi/10.1002/biot.200700148/ab...

4. http://www.nature.com/news/phage-therapy-gets-revitalized-1....

5. https://www.amazon.com/Forgotten-Cure-Future-Phage-Therapy/d...

7. https://en.wikipedia.org/wiki/Phage_therapy

8. http://www.newyorker.com/tech/elements/zero-dark-cavity

9. http://www.usaisr.amedd.army.mil/news/news_stories/2014_FEB/...

I just want to say thank you for a hugely informative, referenced, and brief comment.

You've pointed me at more information on a concept I'm familiar with (bacteriophages), and taught me two new terms -- defensins and antimicrobial peptides.

Clipped & saved.

As much as I love phage therapy (and have loved it for more than a decade now), it's miles away from being as useful as antibiotics, or as functional.

Phages are not universal in nature like Antibiotics which limits their value.

See also the May article in Nature in how we can now create endless supplies of slight variations on antibiotics through semisynthesis to circumvent resistance: http://www.nature.com/nature/journal/v533/n7603/full/nature1...

Previous discussion: https://news.ycombinator.com/item?id=11740340

I think the article above was written off the back of, or at the same time as, some fairly shoddy reporting about antibiotic resistant strains back around March to May this year, because who doesn't want to get in on a decent untreatable rampant killer bug story. It's worthwhile having a read of this:

http://arstechnica.com/science/2016/05/everybody-be-cool-a-n...

Disaster stories sell papers, but the situation is not a disaster story. Rather it is the standard plot for development of new things. People see possible scarcity and react accordingly, far in advance of the non-specialists of the press figuring it out. The scientific community is and has been responding well to the threat of running out of antibiotics. In particular, new advances in mining the bacterial world - a 100-fold enhancement in that mining - mean that we'll be flooded with many new antibiotic drug candidates in the years ahead. For example, see:

https://www.edge.org/response-detail/26701

http://www.popsci.com/ichip-new-way-find-antibiotics-and-oth...

Antibiotics Malthusianism has the same problem as all other forms of Malthusianism, which is that people work to fix the problems they see arising in the future, and resources are far from static as a result.

Thanks for adding this comment. I do think the facts you presented temper the "doom and gloom" sentiment of the article, though the new advancement in bacterial growth has not yet yielded new antibiotic candidates.

> Hospital hygiene is another focus; there is some evidence that staff are more careless about cleanliness than they were in pre-antibiotic days, when they saw deaths like Albert Alexander’s on a more regular basis.

I spent a month at one of the top US hospitals and I witnessed crazy unhygienic practices. The most common one is when the nurse assistant puts on gloves to clean the toilet and other items touched by bodily fluids and then proceeds to clean the food tray with the same gloves and often even adjust the IV lines. I got a lot of nurses angry by pointing this out (it must suck to hear someone else tell you that you're doing your job badly, but still). My mother caught a C diff infection. After that, I carried a clorhexidine bottle with me to the hospital and cleaned all surfaces that contacted food with it.

Hospital-acquired infections have become incredibly common. My grandmother caught a C diff infection after what had already been a very arduous treatment and recovery, and she received basically no support from the hospital that had effectively given her the infection.

While she likely got it in the hospital, it should be noted that a fair portion of the population carried C. difficile in their guts, and could develop a symptomatic infection purely as the result of a disruption of the less hardy elements of their gut flora.

I wouldn't say the staff (as in, doctors and nurses) are careless. It's just that in many hospitals the state hasn't been paying for cleaning services.

There have been multiple instances of rats being found in hospitals, for example.

Here's a source from a few months back. This one was in the pediatric ICU!

http://rederecord.r7.com/video/rato-e-encontrado-em-uti-do-h...

There's a great book called "The Checklist Manifesto" which talks about how simple checklists (of well known, basic best practices) can radically improve medical outcomes.

Seems like cleanliness should be on that type of checklist.

Some modeling work I've done suggests that transmission of hospital infections is possible even at fairly high levels of hand hygiene and no systematic bad actors.

I wonder if there's any correlation between anti-vaxxers and those folks who insist on getting antibiotics that they don't need.

At what point do they just move the outdoor water events to the ocean? I understand it's a hit to national pride to move them, but won't the publicity be far worse if a bunch of athletes get sick?

There are lots of other beaches in Rio that could've been chosen to host the water events.

However, Rio wanted to have some sort of legacy after the olympic games, something to be proud of after spending so much money while people are suffering without health and security. So the governors chose Baía de Guanabara! It's poluted as fuck, but the intent was to cleanse it before the games and have it as the Olympic legacy.

As always, Brazil screwed it and the bay still is a shit hole. Hell, 2 days ago they found in the bay the body of a college student that was murdered nearby.

Source: Live in Brazil. Send help

Finding a body seems unrelated. Even a clean river can get a body now and then...

Drug resistant bacteria found in ocean off Rio http://www.bbc.com/news/world-latin-america-30490396

Publicity? What publicity? From the perspective of the politicians in charge, who cares?

If athletes don't get sick, the politicians get political capital.

If athletes do get sick, the politicians will be nowhere to be found.

Either way, they already made their money in bribes.

Welcome to Brazil.

I'm confused. What's the relevance of this to the posted story - "Antibiotic resistance: The grim prospect"?

Superbugs were found in the waterways of Rio de Janeiros, which is hosting the Olympic Games.

This is such a clickbait title. It's like saying "Dogs that can learn tricks discovered in NYC".

Thanks, we've updated the title to that of the article.

Link points to a piece from The Economist, from a month and a half ago, not to current news. Please change the title.

I'll do. Thank you...

Can you say clickbait?

We've been on the cusp of an antibiotic resistance epidemic (according to the media and select physicians) for decades.

1979 - http://www.ncbi.nlm.nih.gov/pubmed/45521

1992 - http://science.sciencemag.org/content/257/5073/1064

But, as @reasonattlm said far more eloquently than I: humans seem need these stories to provide the motivation to use existing antibiotics less and to get moving on creating new antibiotics.

humans seem need these stories to provide the motivation to use existing antibiotics less and to get moving on creating new antibiotics.

Are drug company executives humans ^_^?

Because one of the biggest problems in bringing new ones to market is that after you've spent more than a strategic bomber getting them there, they're put on last resort lists ensuring they won't get prescribed often. To even come close to breaking even they have to have seemingly insane prices, which gets them horrible PR for the crime of saving lives in a system that's stacked against them.

Why bother? I'm sure a lot do because they don't want them and their's dying from a superbug in the future, but they've still got to keep their company out of bankruptcy.

Sure, but it is a real problem. Many antibiotics that were useful in the past are much less useful now, and more antibiotics with undesirable side effects are being used as treatments of last resort. If nothing had been done to mitigate the issue since 1979 or 1992 we'd be in a pretty dire situation by now.

Not really, new resistant strains and new antibiotics to fight those strains is a constant inevitable march of evolution, and for the most part, driven by money from large pharma companies. An equivalent might be murphy's law and silicon chips.

It's hardly dire, and arguably the disaster headlines of each new MRSA strain is more damaging to public awareness about how antibiotics actually work.

Not may researchers agree with this view. Note the decrease in discovery of new antibiotic over time. Cite: http://smellslikescience.com/a-need-for-new-antibiotics/ Also if you need more info, more people are estimated to die from AMR then cancer in 2050. Cite: http://www.bbc.com/news/health-30416844

That's given the techniques used so far. See the recent work by the Lewis group [1] which uses a new method to culture soil bacteria to identify new antibiotics and opens up an entirely new pipeline. Previously, we've never been able to keep these strains of bacteria alive, but now we're able to allowing for sequencing and isolation of tons of new antibiotics. It's estimated that we'll be using this new technique for a long time.

New antibiotic finds are black swan events, they tend to come from new areas that unless you specifically are looking there, you're not going to find. It's like an oil well, and the usage of the the few "last-resort" antibiotics, which ones get produced and sold, is highly controlled by a handful of pharma companies so they eke out whatever monetary value is left.

[1] http://www.nature.com/nature/journal/v517/n7535/full/nature1... https://directorsblog.nih.gov/2015/01/13/digging-up-new-anti... http://www.the-scientist.com/?articles.view/articleNo/41850/... http://www.npr.org/sections/health-shots/2015/01/07/37561616... http://www.smithsonianmag.com/science-nature/new-antibiotic-...

"That's given the techniques used so far." By definition, looking at history does precisely that.

I am familiar with Lewis group and and wish more people were also. Thanks for the links, as its nice to see the background for those not familiar. Definitely worth an upvote IMHO.

My concern with this the belief that this is is a steady march where "New resistant strains and new antibiotics to fight those strains is a constant inevitable march of evolution" implies there is no need to be concerned. New technology may save lives, just as unproven carbon neutralizing tech may stop green house issues, but today, at this moment, there is no proven tech that obviates this dangers. While, we hope and believe, that new tech will solve many problem, the widely held scientific view point on AMR is that it is an unsolved problem that is going to kill a lot of people. Which IMHO is pretty dire.

My point is, the inevitable march is driven by the market pipeline created by the Glaxosmithkline, Merck, and Amgen's of the world more than anything else. A good black swan event disrupts this to some extent, but not really. As long as there is a new MRSA, there is a host of new antibiotics being developed. This means there is always an arm race that requires lots of investment, but this pipeline we have set up today is far from optimal. Changing IP rules is a good place to start.

> ...to provide the motivation to use existing antibiotics less...

But always complete your antibiotic prescription.

This bit of folk/medical wisdom has been around for a few decades, but for the life of me I can't understand the logic - beyond the notion that merely being asymptomatic doesn't mean you've killed all the bugs.

How this can possibly contribute to the spread of antibiotic resistance is mystifying to me, as is the basis of this advice - is there ANY evidence that patients not completing their drug courses causes resistance?

Absolutely!

As I learned as a rule of thumb while doing microbiological research in a NSSF Summer Science Training Program in 1977, most random antibiotics would fail to kill E. Coli at a rate of 1 in a million, and it went up to 1 in a billion with streptomycin (this is with random mutations, no plasmid acquisition involved, which is another story).

However, these surviving bugs are generally not as fit as wild type, they've probably survived by sacrificing something, or doing something that consumes more energy. This helps your immune system mop them up, and note if antibodies are involved (don't know about that) it takes a while to come up with new ones, plus if there's any sort of bacteria ecology in the target area that survives the antibiotic they'll out-compete them.

It shouldn't take much research on your part to confirm the basics of what I've related above, it's a tremendous problem, especially with TB, who's defenses require long and obnoxious drug schedules, resulting in more and more MDR and XDR (multi- and extensively-drug resistant) strains.

If you get XDR, you're probably going to die, in a era where that's squalid instead of romantic.

And I just came across "Totally drug-resistant tuberculosis" https://en.wikipedia.org/wiki/Totally_drug-resistant_tubercu... Not official yet, but....

As I said, completing your course is useful in eliminating residual disease. How does it help in preventing drug resistance? If anything it seems by increasing exposure to the drug it encourages the development of resistance, since it gives the (otherwise less-fit) resistant bacteria a fitness advantage. Completing a course of a drug that the bacteria is already-resistant to will accomplish nothing other than eliminating its non-resistant competitors, so what's the logic?

Errr, the theory I'm relating is that continuing the pressure of the antibiotic will make it easier for the body, and perhaps non-susceptible benign bacteria, to finish them off (perhaps not all, but to a de minimus number where they won't pose a problem).

Remove that pressure, and the resistant population has a chance to rebound. More likely than having an ecology of other bacteria to fight with is that the field is somewhat or all but completely cleared. The body may not also have had a chance to clear up whatever condition allowed it to get a grip in the first place. Etc.

Again, as I understand it TB is a great example to look at, and depending on where you live it might even be a real danger to your and yours, so maybe read up on it?

What's curious about this view, is that it ignores how researchers create AMR bugs in the lab. Namely low doses of Antibiotics to allow time for the bacteria to mutate and develop resistance. If you're interested you can look up MIC Minimal Inhibitory Concentration, I think you would find it illuminating. Also the assertion that the resistant phenotype is "otherwise less-fit" is not accurate.

The resistant phenotypes often ARE less fit, as the guy above me said - if you have to run a solute pump in order to remove drug from your cytoplasm, that has a cost in energy and protein. EVERY phenotype has a cost that must be paid. You don't get to hang onto a useless genotype in the absence of a selective pressure that maintains it.

Low doses allow you to provide a continuous challenge that doesn't kill the entire population. That's not what's happening when you stop your drug course early.

DNA absolutely hangs on to useless genotypes for some period of time. Horizontal gene transfer allows for redundant genes to exist. They have increased mutation which MIGHT lead to some productive change, but for an extended period of time they don't. Not to mention biological mechanism which exist for many many generations even though they aren't used in some grow medium. The disagreement here is about time scale.

If it were true that resistant phenotypes often ARE dramatically less fit to the degree you imply we could simply stop taking Antibiotics and everything would revert back to it Susceptible state.

When you stop a dosage early you've very likely applying a low dosage to some subpopluation. Dosages are not linear, nor evenly applied throughout the entire population of bacteria in a human body.

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