This is a public health crisis that needs urgent attention. Governments should step in with huge funding to NIH and pharma to accelerate R&D, and offer incentives to invest heavily in antibiotic development (extended patent terms for antibiotics, tax-free repatriation for antibiotic R&D funds, whatever it takes).
The current free market approach is completely failing this. It's not particularly profitable to invest many years in a drug people only need to take once to cure a disease when compared to developing a drug people need to take for 5-10+ years to manage a disease.
Phage therapy should be further developed as well, which has been proven to work against some resistant strains.
>The current free market approach is completely failing this. It's not particularly profitable to invest many years in a drug people only need to take once to cure a disease when compared to developing a drug people need to take for 5-10+ years to manage a disease.
Why couldn't their payment scheme be identical even if it's a one time dose? Instead of $1000 per year for a drug you need to buy every year for ten years, make it so it has an up front cost of $12,000 or whatever with a ten year payment plan available for people who don't have that kind of cash on hand. This suggestion obviously inspired by the real world good that is a one time purchase that people make all the time: houses.
But to elaborate, aside from the obvious ethical implications, there are also practical differences. You are usually not forced out-of-the-blue to buy a house, no matter if you can afford it or have just bought a house last month. Also, houses can be sold, so people have ways to back out of a purchase when they realize they cannot pay back the loan. None of this works for drugs.
Trying to apply the same logic to drugs would make the the debt problem of medical bills even worse than it already is. It would also lead to a strong inequality in medical care.
Isn't Martin Shkreli notorious for hiking prices on drugs, not for pioneering new payment models for drugs? My post was about how if a company had a drug which it had development cost $X for, it could recoup X + p from the consumer even if the drug is a one time dose rather than an ongoing treatment. How much p profit they make is a separate question and anyways is sort of orthogonal to the question of whether they pay per month or once.
This is what should happen. If you price a drug based on the value it offers, antibiotics should cost a lot more than they do now. You're talking about a single treatment regimen that often saves the patients lives.
The problem with that approach is the way that hospitals are reimbursed for antibiotics in the US. There is no room for those prices. I know Congress is trying to change that by making antibiotics separately reimbursed.
[Source: I worked at a biotech firm that has a number of antibiotics in development]
Teixobactin unfortunately isn't helpful to us. We really really need something that works against gram negatives at the moment.
Also note that retrospective studies have shown that first observed resistance to an antibiotic appears about six months after it is introduced. We are producing new antibiotic families far slower than this rate.
Articles like this urge me to stop reading pop science journalism altogether.
What is not mentioned is a new class of antibiotics discovered in 2015 (https://en.wikipedia.org/wiki/Teixobactin) which is a big deal in that it can be used instead of antibiotics resistance to which has been acquired by bacteria during this "golden age" and as microbes evolve extremely fast, within an observable timeframe they will lose resistance to the old classes allowing those to be used again. So effectively shelving will work.
Its incredible that so far there's no evidence of resistance development with Teixobactin. It prevents cells from building cell walls. There may not be an evolutionary path for bacteria to stop this kind of thing or if there is, its a very slow path that might mean decades before resistance begins to show instead of the standard few years. Still, its limited scope. Works well with staph, but does nothing for other infections like e.coli, salmonella, and h.pylori.
The funding purse is open for antibiotic research and I find it hard to believe its a dry well. I think we'll see more discoveries like these in our lifetime.
Any references detailing the shelving method? I'm genuinely interested, especially about the necessary timescale etc.
I absolutely agree that it won't be as gloomy as outlined in the article. The search for novel antibiotics has been pretty much neglected (Teixobactin is more of an exception to the rule) because the currently employed drugs work quite well. As this is changing, the possible market for novel antibiotics will increase and thus funding will shift into this direction.
There's a Radiolab podcast [0] about the revival of a 1000 year old antibiotic from an old medical text. Towards the end they discuss theories as to why something that appears to be tremendously effective was somehow lost to time and one likely explanation is this "shelving" effect.
I can't find anything by google, but the basic approach is probably as follows, because it makes sense: Pick a class of antibiotics that you want to remove resistance to. Stop using it. Completely. Use other antibiotics more aggressively. Selection pressure toward resisting your still-in-use antibiotics will direct evolution's optimization power toward fixing traits to resist them. If you're lucky - and I think we are, for the most part - antibiotic resistance is metabolically and/or genetically expensive, so the traits for your shelved antibiotics will be gradually lost, or even better, actively selected out. Some time down the road - I don't know how long - your shelved antibiotics will be back to full power, and you can shelve your still-in-use antibiotics out and rotate your shelved antibiotics back in.
Ideally you have enough different classes of antibiotics that you can maintain a constant rotation and always have new antibiotics coming off shelved status so you can retire antibiotics that've formed resistances. Even better, a larger library of antibiotics directly improves the effectiveness of this strategy - in the short term, introducing a new class means you can shelve an old, resisted class; in the long term, more classes means each class can spend longer on the shelf and we reduce antibiotic resistance further.
The only problem I see with this strategy is enforcement of the shelving. If someone is sick, and a "shelved" antibiotic is all that is available to them, they will probably take it, effectiveness be damned.
Current antibiotics are getting progressively less effective and if doctors prescribe the newer more efficient classes (once they are available), the incentive to get old ones are negligible.
Bacteria are minimalist (http://www.sciencedirect.com/science/article/pii/S0092867402...) which tends to amplify the use it or loose it evolutionary principle. There's a certain cost to keeping a "feature" in an organism that small with a high rate of mutation and adaptability.
"Strains of bacterial pathogens that have acquired mutations conferring antibiotic resistance often have a lower growth rate and are less invasive or transmissible initially than their susceptible counterparts." http://aac.asm.org/content/54/5/2085.full
If evolutionary logic holds (and there's little doubt about that, though research on the rate of resistance lose with time varies), switching to new classes of antibiotics and not using old ones until resistance to them de-evolves is a viable strategy.
But how long is that going to take? Resistance has very high fitness in the presence of humans using antibiotics (avoiding death); resistance has very small negative fitness in the absence of humans using antibiotics (saving a tiny bit on metabolism). However long it took to evolve resistance, it'll take many times longer to de-evolve it. And given randomness, a tremendous number of copies of the resistance genes will hang around anyway so the resistance will come back even faster the second time.
I imagine antibiotic resistance is not just an on/off switch in a vacuum, i.e. a different chemical surface might interact differently with a drug but also have some adverse effect, so losing the resistance would be advantageous.
Too long. You can get significant mileage out of a 3 year ban but resistance will return very quickly afterwards. You'd need to wait decades to truly reset the clock.
> After three years of banning the use of that antibiotic, the resistance of the bacteria dropped significantly. But because there were resisitant strains that persisted right through the end of the study in 2008, it was likely that the resistance would surge once again if the antibiotic were reintroduced. To safely reintroduce the antibiotic, Townsend said, you have to kill off all the pathogens.
> Considering how important antibiotics have become to human health — from the treatment of strep throat to MRSA to tuberculosis — Townsend says a 45-year ban on most antibiotics would be impractical. Doctors estimate it takes about that long for the resistance to disappear.
There's tremendous political problems with just "not using them" - we've done shelving before, usually with drugs that have unfavorable characteristics. Colistin is one example, it was shelved because it's fairly nephrotoxic, and today it's one of the last-resort antibiotics.
The problem is China loves to pump their livestock full of it to boost production, and now we're starting to see bacteria strains that are resistant to it.
The foreign use of drugs-of-last-resort is what's specifically concerning, and what raises the questions of the WHO's ability to coordinate and enforce shelving.
The use of common antibiotics isn't good, by any means, but last-defense drugs being used is far worse.
A colony of pig microbes getting resistant somewhere in China to an antibiotic rarely used to treat people, might not be that big of a threat if spreading of the bacteria is contained. It even might be that most drug-resistant colonies just die out locally. How many human cases have been registered of Colistin resistant diseases?
The fact that a drug of last resort is being widely used in livestock is actually quite concerning, because it still builds resistance to this antibiotic even if it's not being used on humans. It also raises huge questions about the ability to enforce shelving.
At least two cases have been detected in the US, the first was earlier this year, the second as of yesterday.
As mentioned in the article, the colistin resistance is being transmitted via plasmid, so it is capable of diffusing quite widely into different types of bacteria.
That's good and all. But is there regulation to prevent the livestock industry from using it indiscriminately? It doesn't matter much how awesome it is now if we're going to fritter away its effectiveness in a few years.
Teixobactin is cool, but if it's only active against gram positives, it's never going to work against most of the bacteria listed in the article: E. coli, Salmonella, Klebsiella, N. gonorrhoeae, etc. Most of the terrible new drug resistance genes are showing up in gram negatives.
Sure, new methods of finding antibiotics are in the works, although the article you link has plenty of experts recommending caution about their potential. The bigger point is that in 2016 there is a looooooong road from antibiotic "candidate" to FDA-approved drug. That road involves decades of trials and costs billions of dollars per approved drug.
The larger problem is that there is little if any incentive for pharma companies to invest in antibiotics compared to traditional blockbuster drugs that are supposed to be taken chronically (and therefore have better ROI). It's the same reason little R&D goes into making new vaccines. It doesn't matter how many candidates are found if they can't make it to market in a timely fashion (the point of the CDC bar graph), and this is what the "slow catastrophe" really is. It is not that scientists will never figure out new ways to kill bacteria.
>That road involves decades of trials and costs billions of dollars per approved drug.
Only because we've had time as a luxury in the past. I imagine new variants will get fast tracked. FDA bureaucrats hoping to lazy their way to retirement will be under a lot of pressure to actually get things done quickly when there's so much social need. No one wants to be the POTUS who didn't fast track life saving antibiotics if they're shown to be generally safe in early testing. The FDA is a government organization and as such is subject to the politics of our leadership and indirectly, the electorate.
It's not as easy as that. Take the meat/poultry/milk products industry. In the EU, legislators have done a net-good for humanity by aggressively issuing legislation restricting antibiotics and growth-hormones. This is widely accepted as good for humanity as evidenced in this seminal article[1]. The sword cuts both ways.
See also: vehicle safety features like airbags, seatbelts, crumple zones, child car seats, safety testing, etc. Collectively, they've helped drop car crash injuries and fatalities enormously.
> Because humans, without regulation, don't value vehicle safety. Gotcha.
Basically. Humans are horrible at cost/benefit calculations on an abstract level that may not directly affect them for years or even ever on an individual scale. I've known people who won't wear seatbelts because someone they know got trapped by one in a freak accident, despite overwhelming statistical evidence that's a dumb approach. The industry also has a long history of fighting regulations that require safety features but make cars more expensive.
> Last month, Ford proposed weakening the transportation department's 1984 rule in exchange for faster introduction of air bags in its cars. The company offered to install the bags on the driver's side of a majority of its cars by the 1990 model year if the department would drop its requirement that the front seats of all cars be equipped by then with automatic or so-called passive belts, designed to restrain the passenger as the car door closes.
> A Federal Motor Vehicle Safety Standard proposes that all vehicles made after January 1, 1973, include an automatic restraint system, i.e., air bags or automatic belts. The auto industry, knowing that it would have to increase production costs to meet the new standard, balks, leading to a decade of argument and delay.
The automatic belt systems also had the disadvantage of being fiddly, unreliable and complex. While the airbag is not as effective without belts, its much more reliable, and much less complex mechanically than automatic seatbelts.
That's hardly the only piece of tech the car companies have fought. Air bags and shoulder seat belts, among other things. The National Highway Traffic Safety Act of 1966 appears to be pretty universally cited as the turning point from a rapidly increasing rate of automative deaths to a dramatic, sustained drop over the next few decades.
I am painfully aware of what totalitarianism is... Should I not talk about it and warn against it until it's undeniably here? Sometimes it is very hard to figure where you would draw the line on political influence.
Telling a car manufacturer to design a vehicle that doesn't kill it's occupants ishardly totalitarianism. Calling it such does a disservice do everyone by conflating helpful laws with actually totalitarian things the government does.
And I can almost guarantee that this has negatively effected the purchasing power of those least well off in the EU. Along with other various detrimental unintended consequences. Which is why, morally, this is wrong through force. If I want to eat growth-hormone free meats, that's my choice. This "net-good" talk is nonsense.
All I see when I read that is, it should be my choice to kill hundreds of millions of people. This is about more than say the deaths from say the Holocaust, this is about more lives than where lost in all of WWI and WWIII combined.
Antibiotics have already saved ~200 million lives, 80% of their use is in livestock, and they are of limited long term value. A reasonable guess is a Billion+ lives hang in the balance.
And, as usual, you are quickly pulled into the straw-man: "well if you don't want government to solve it, than you don't want it solved". I don't want to forcefully deprive the poor of food, that is true. I don't really want to forcefully do anything.
We convinced millions of people they'll feel better if they don't eat gluten. An entire cottage industry created. All without force. All without the influence of politics and fallible men.
> We convinced millions of people they'll feel better if they don't eat gluten. An entire cottage industry created. All without force. All without the influence of politics and fallible men.
How do you make the logical leap from "a big diet fad happened" to "the FDA is redundant and evil?"
>And I can almost guarantee that this has negatively effected the purchasing power of those least well off in the EU
And I can guarantee absolutely that purchasing power is not the be all end all, and that leaving it all to the free market and "if I want X, it's my choice" creates more issues than it solves. For example, nobody labelling what they sell as X (but as X+, the better variety), without legislation to prevent them.
And the same argument goes to BS like avoiding vaccination and people teaching Creative Design to their kids.
The differences largely result from stuff like that fraud, ethics failures, and other issues we've run into in the past.
Just like Bitcoiners rediscovered the reasons our financial system has the various moving parts it does, healthcare regulations tend to have good reasons behind them.
Discussing FDA type regulation you need to consider both costs and benefits. As with everything else, of course.
The Thalidomide argument points out the benefit: These regulations avoid releasing medications with bad side effects to the population. Nobody denies this is a good thing.
The costs are more rarely discussed. I think these are the main ones
1. When approval of a medication is delayed 10 years, everyone who would have been cured/helped by it during that time pays. Often with their life.
2. The high cost of FDA level trials makes medication more expensive. It also makes some medications economically unviable, with similar costs as in 1.
I'm not aware of any study trying to quantify these effects, but my wild guess/gut feel is that the costs are ~100 times bigger than the benefits.
The PR problem is that victims of bad medications are seen. The Thalidomide sufferers became world famous. But the ~100k Americans who died while the FDA took 17 years extra to approve beta blockers had no idea why they died.
Having worked a bit in the industry, changes in regulation aren't actually the main problem. There are two trends combining: some tightening of the rules, yes (although the 'hockey stick phase of regulatory interference' was after WW2) and, much more importantly, a complete collapse of research success.
We're still basically following the process established in 192x (Bayer, sulfa drugs) of throwing any structure we can think of onto some essay, into some mice, then humans. Educated guesses have become more educated, but not much better.
Regulation has only become a burden because we're chasing ever-decreasing improvements. Even placebo got better over the last decades, which may have doomed a few potential blockbusters.
It's obviously a problem of the lower-hanging fruits having been picked, and not all is bleak (kicking HIVs butt these days). But a cell just happens to be 35mill lines of self-modifying, multi-layered, self-evaluating, quantum-effects-using complexity and we're far away from a rational, hypothesis-driven drug discovery process.
Deregulation wouldn't actually help. While it is possibly attractive for a patient now, that comes at a certain and significant disadvantage for future patients: If you could sell everything you wanted, there'd be no incentive for studying efficacies – it'd just be random stuff that may work, competing in a dysfunctional marketplace.
Dysfunctional because nobody would know anything. Even with the somewhat professional studies we have today, and even for professionals, it is a major undertaking to form a solid opinion on a drug. Throw in patients who have nothing to lose and it'd probably be worse than it ever was.
It's not like experimental treatments aren't available today. Almost every cancer patient is enrolled in one or more trials, unless she immediately responds to existing drugs. Quite a few people have traveled to Asia for some stem cell snake oil (less money, nice tan, no improvement, life-threatening complications being the usual outcome).
We do however have both historical examples of pre-regulation pharmaceuticals and the supplement industry to examine, and neither one is a shining light of efficacy or safety.
You can't cherry pick victories and ignore the failures. Hell, I was on Vioxx for a while and now have to worry about heart attacks and strokes more than the average person. Gee thanks FDA!
The FDA also has a long history of whistleblowers to fight FDA corruption. Drugs like Avandia and Rezulin should give you pause.
Yes, lazy bureaucrats, rubber stamping, politics, and monied interests work together to make FDA approval a crap shoot. I never understood this whole "worship the state" aspect millennials subscribe to. The state has its own agenda and its usually counter to yours.
I have read all your comments -- including the doozy "all...without fallible men" -- and I will suggest that:
A) If you are incredibly savvy, you can already sidestep government regulation by pursuing remedies outside the scope of what they control.
B) Most people are not that savvy and, unfortunately, need the protection provided by government regulation.
C) There is zero means to remove the fallibility of "men" from the equation. (I am a woman. As much as I would love to joke that things would be so much better if women ruled the world, the reality is that the fallibility of humankind is inescapable. Also -- cough -- Theranos.)
D) Antibiotic resistance is not due to lazy bureaucrats. It is due to lazy humans. It's lazy humans all the way down. They are hardly confined to government.
E) Even in alternative med circles, you get social pressure and people with a profit motive and conflict of interest and on and on.
F) The path to solve this will never catch on. It is too much work. It can be done now. The research into how to break up biofilms is already at a useful stage, if you are sufficiently motivated.
G) Gosh, I wish you would step away from this discussion. You aren't adding any value here.
I used to work at an antibiotic discovery startup.
I used to joke that there were so many groups with a Gram+ antibiotic drug discovery program going that my parents were probably running one out of their cellar.
Many antibiotics classes seem to be partially selective at killing either Gram+ species or Gram- species.
For example, fluoroquinolones can kill both Gram+ and Gram- microbes, but they are generally better at killing Gram-.
Other classes have the reverse characteristics.
I don't know much about the types of microbes that cause periodontal disease.
However, my company was initially interested in treating Community Acquired Pneumonia (CAP). The problem with CAP (and many other bacterial infections) is that they can be caused by either Gram+ or Gram- pathogens. This means that if you're making a drug to treat CAP, you need an antibiotic that can "hit" both types.
A common occurrence when we were looking for a candidate drug that could treat CAP was that the candidate would be powerful at killing Gram+ CAP microbes and weak at killing Gram- CAP species. If we improved the drug's ability to "hit" Gram- species, we would always seem to lose potency against Gram+. It was extremely tricky to find something that was powerful enough against _all_ the relevant microbial pathogens.
That's freaking fascinating, I'm in bioinformatics myself, I'd love to hear more about this- I wasn't aware that an antibiotic discovery startup was/is/could be a thing at all- If you can tell me anything more or put me on the right track to reading more about your old employer in that space or whatnot, I'd appreciate it! :)
But these startups do exist: look up Achaogen (achaogen.com) and Tetraphase (tphase.com).
Cubist Pharmaceuticals was a big antibiotic developer that was recently purchased by Merck. Cubist itself bought another startup called Trius Pharmaceuticals, which had developed a newly marketed antibiotic.
So, there is $$ to be made in antibiotic drug development, but as many people on this thread have pointed out, there is more $$$$ to be made in other therapeutic areas (e.g., oncology).
You're right about incentives being wrong, but I disagree with the preference for chronic drugs being a primary factor. In my opinion, the primary incentive killer is that agencies like the FDA will not approve a truly new antibiotic for general use. It gets approved as an antibiotic of last resort. So for the time that a new antibiotic is under patent protection, the company can't recoup their R&D because they can only address a tiny part of the market. When the day finally comes when the wonder drug can be standard of care, it's well off patent and generic competition torpedoes any real profit. Why develop a great new antibiotic if the FDA forces you to keep it locked away? From the company perspective it makes no sense.
Hmm, well as a counterpoint to your point about the FDA, fidaxomicin was approved in 2011 for general use against C. difficile colitis, because it showed certain outcomes that compared favorably against the current standard of care (oral vancomycin) [1]. The reason it isn't used more often is probably because it is one of the most expensive antibiotics available. Antibiotics aren't typically approved only as "last resort"; it remains at the discretion of the physician to jump straight to the big guns before drug susceptibility test results are available (which is part of the problem).
You're right about incentives being wrong, but I disagree with the preference for chronic drugs being a primary factor. In my opinion, the primary incentive killer is that agencies like the FDA will not approve a truly new antibiotic for general use. It gets approved as an antibiotic of last resort. So for the time that a new antibiotic is under patent protection, the company can't recoup their R&D because they can only address a tiny part of the market. When the day finally comes when the wonder drug can be standard of care, it's well off patent and generic competition torpedoes any real profit. Why develop a great new antibiotic if the FDA forces you to keep it locked away? From the company perspective it makes no sense.
If I'm not mistaken, resistance usually comes at the cost of some efficiency. Drug resistant bacteria are outcompeted, which is why resistance fades in nature.
My crazy theory is that somebody with drug resistant TB could be deliberately infected with regular TB, which will replace all the DR TB, and then you treat the patient normally. Assuming they survive.
> What is not mentioned is a new class of antibiotics discovered in 2015
Call us when any of them survive the valley of death that kills 99%+ of substances with interesting in vitro activity to reach clinical use and the hypothetical becomes actual. In the mean time, real people are dying real deaths.
As if you didn't read about Teixobactin in pop science journalism. Even if Teixobactin is the solution it won't get through all testing and regulatory steps for many years. And even then it would probably be extremely expensive.
Seems like this is time to research how antibiotic resistance is jumping species. I feel like we could take advantage of unauthenticated exchange of information and inject weaknesses instead.
Basically, when bacteria discover a gene that works, they share it with others. As far as I know, this does not readily lend itself to a human counterattack of some similar approach. The solution will likely come from some other avenue.
You have to live to share. So, the distinction is essentially immaterial. They find something that works, they live, they share randomly for kicks with other bacteria they picked up at the bar, those bacteria become resistant, rinse and repeat.
How about we "share" something with the bacteria? We create a package, and they pick it up, and it turns out to either kill them outright or leave them vulnerable to some simple treatment.
> Artificially constructed plasmids may be used as vectors in genetic engineering. These plasmids serve as important tools in genetics and biotechnology labs, where they are commonly used to clone and amplify (make many copies of) or express particular genes.[12] A wide variety of plasmids are commercially available for such uses. The gene to be replicated is normally inserted into a plasmid that typically contains a number of features for their use. These include a gene that confers resistance to particular antibiotics (ampicillin is most frequently used for bacterial strains), an origin of replication to allow the bacterial cells to replicate the plasmid DNA, and a suitable site for cloning.
I think that the problem would be coming up with a delivery method.
Microorganisms have been able to cope with each other for damn near a billion years using toxin-antitoxin systems. People are exploring these as negative selection systems. Traditionally, antibiotics are used. http://nar.oxfordjournals.org/content/early/2015/03/23/nar.g...
There is probably a huge array of such things out there. They are unlikely to be as broad-spectrum as traditional antibiotics, but with research we should be able to find ones to apply to the right situations.
At the same time as this crisis unfolds, our ability to know exactly what someone is infected with improves. Soon sequencing of bacterial infections will be the first step in patient triage. This will help us apply precisely the right toxin to rid the body of the problematic type(s) of bacteria.
This seems to be an alternative approach of tackling said infections, sadly research in the EU has been blocked by Big Pharma for years, at least in Germany very successfully to be precise, noone with a slight of reputation is going to touch this topic.
I wonder why.
It does work under the conditions described as far as i can understand.
The Georgian Institute that does most of this research is well underfunded too.
Phage therapy is neat, it really is, but there are a couple major issues:
- There is no such thing as a "broad spectrum" phage. You can't do empirical treatment using phages, and there's not really "off the shelf" phage therapy - it tends to be a bespoke creation for a particular infection.
- There's some serious regulatory problems, similar to those experienced by fecal transplant treatments. We're not yet really equipped to think about handling evolving, custom microbes as a treatment.
- Because of the first, it's going to require a considerable amount more lab capacity than most clinical settings currently have, and considerable delays until treatment.
- There's also some biosafety issues around phage prep, but those are easily solvable.
It's a great way to treat particularly resistant or hard to treat infections, but it's not a particularly great general solution. There's a reason it was abandoned in countries with easy access to antibiotics - they're just roundly superior in basically every respect.
This is to be expected. The big issue is that it is not worth it for a pharmaceutical company to develop new antibiotics. The initial cost is high. Then, if it is successful, the antibiotic will only be given as a last resort, thus reducing the number of doses. In addition, unlike chronic conditions such as diabetes or high blood pressure, severe bacterial infection is usually time limited - the patient will either get better or they will die. In either case, they do not continue to need the antibiotic. Thus, to recoup costs, the pharmaceutical company will have to sell it at low volume/high prices. Of course, if they do that, the press starts blaming them for the high cost of the medication and it is a PR disaster (see Sovaldi) even though everyone is strictly better off due to their selling the antibiotic even at a higher price. In the end, it is better for their reputation and their bottom line not to develop these antibiotics. Thus, mainly because we do not have aggressive new development of antibiotics for these severe infections, we have these articles claiming the end of the antibiotic age.
And in response to that, the pharmaceutical companies will sell the antibiotic in high volumes to the livestock industry. Thus increasing profits... forever!
With the nice side effect that this will spur more resistances, hence more reasons to develop new drugs, that they can sell at higher prices, driving profits even upper.
It's nice to get paid to solve a problem you created in the first place.
Ummm... human and animal health are usually separate companies. I know Pfizer had an animal health unit, but it was spun off. Those are two different groups of companies you're talking about.
When an organism develops resistance it usually makes an evolutionary trade-off. This ironically might make them susceptible to older style antibiotics who have been phased out. However retesting these antibiotics are not really being done extensively due to there being little financial benefit.
My experience with kids is that here in Spain they are using older antibiotics now to preserve the newer ones for serious infections trying to limit evolutionary pressure on the bacteria.
Antibiotics resistance is getting stronger, probably because people eat a lot of meat which is full of antibiotics. Because they feed animals with antibiotics to grow faster and bigger. People should really think what food they put in their body and less about some magic pill.
So there are two issues that are touched on here, which are not really expanded enough.
1) farmers everywhere are allowed to use last line/new antibiotics routinely in food production. This is utterly fucking stupid. Whats more brain dead is that its not just china its US and canada. (possibly the EU.) It could be stopped by the FDA withdrawing the license. but no. Too much money.
2) over subscription in private health.
I once listened to a co-worker phone up the Doctor and ask to have "the same antibiotics I had last time for that cold" and get it[1]. She had the fucking snuffles. No consultation, not even bothering to figure out if its even got a hint of bacterial infection.
A placebo would have been more effective. It wouldn't have given her the shits either. Paracetamol is what was needed, as its the only thing that would have made her feel better.
Seriously. yes I know that the customer is always right, but don't fucking dish out drugs like sweets. My old age, and my children's health are dependent on those drugs.
[1] yes this was in the USA, santa monica to be precise. Yes I'm british. However the prevalence of prescription medication abuse and deaths is a massive fucking warning. Something is horridly wrong with the US's health care system.
What surprises me is with the levels of litigation against doctors, this hasn't seemed to trigger any change in behaviour.
1) farmers everywhere are allowed to use last line/new antibiotics routinely in food production. This is utterly fucking stupid.
Basically, it's exactly the worst thing you can possibly do, with regards to what the theory of evolution by natural selection tells us. Then add in what we know about bacteria exchanging genetic material, and it's like we're trying to inactivate all of our antibiotics on purpose.
>Basically, it's exactly the worst thing you can possibly do, with regards to what the theory of evolution by natural selection tells us.
from the half-full glass POV we are just speeding up the natural selection of bacteria resistant humans (it has been going for millenia and got, probably only temporary, delayed for the last 80 years). Also, as a side effect, it can help solve (at least temporarily) the overpopulation issue until the much more smart (wrt. health and Earth resources usage) humans evolve. Basic dialectics at work.
from the half-full glass POV we are just speeding up the natural selection of bacteria resistant humans)
Often, what's good for species evolution is really bad for some individuals. What good is a half-full glass to you if you're dead?
Also, as was noted elsewhere in the discussions, evolutionary pressure for bacteria to attain an immunity is high, but pressure to lose one is usually much lower. However, bacteria are small, and such pressure is higher than in more complex celled creatures. "Shelving" antibiotics does work, but would require widespread cooperation and the curbing of feeding antibiotics to livestock.
Having antibiotic failure as the method for arresting the massive human population (7B people) would require carnage that makes World War II (~70M deaths) pale in comparison, even if you correct for the lower global population of the day.
Disease has typically killed more than wars. The Spanish Flu epidemic of 1918 killed 50-100 million people, several percent of the total world population. By comparison, total military and civilian dealths in WWI were about 16 million.
Oh, I agree - I just used WWII as it's a more commonly-understood datapoint. The Spanish Flu epidemic only took a couple of years as well, as opposed to the half-decade of WWII.
"sterilizing" means destroying the ability to produce next generation. No dying involved. It may be some very light infection, just with a sterilizing side-effect for example.
> from the half-full glass POV we are just speeding up the natural selection of bacteria resistant humans (it has been going for millenia and got, probably only temporary, delayed for the last 80 years). Also, as a side effect, it can help solve (at least temporarily) the overpopulation issue until the much more smart (wrt. health and Earth resources usage) humans evolve. Basic dialectics at work.
Bacteria evolves resistance at about the same rate as people develop defenses.
So yeah, if you don't mind killing off a huge segment of the population and having women die in childbirth regularly.
The UK has had a campaign asking patients not to ask for antibiotics for a cold or flu (and presumably asking GPs not to prescribe them), and also reminding patients who are prescribed antibiotics to complete the course, but it must be impossible to regulate, particularly in a more capitalistic health system.
Disclosure: I live with a doctor.
Irrelevant aside: Rare to find someone on HN call a disclosure a disclosure, rather than the oft-abused "disclaimer"! :)
Doctors are learned professionals, and they have a professional responsibility not to prescribe ineffective medication. Importantly, antibiotics come with their own substantial risks. A whiny patient is not a good reason, and I've never met a doctor unwilling to turn down a whiny patient. It's only at the margins where a whiny patient can cajole a doctor, such as to increase dosage. Plus, whining is one piece of evidence used in diagnosing, and if the doctor has others reasons to believe there's something substantive, whining can nudge him along.
The _crux_ of the issue is that doctors prescribe antibiotics for viral infections because the diagnosis is usually only based on a cursory examination. Their time is expensive, and you can't spend an hour on every patient with a cough and a fever. Furthermore, viral infections often precede or are concurrent with bacterial infections. So doctors are making a rational decision when prescribing antibiotics, and it's not even clear that this decision is globally suboptimal because bacterial infections are not uncommon with a cold or especially a flu.
If we're serious about overprescription of antibiotics, we should be heavily investing in improved diagnostic equipment and processes. For example, rapidly scanning mucus samples for viral and bacterial markers. The fact that we don't appear to be doing this suggests that either overprescription isn't actually a problem, or that we're not thinking seriously about the problem.
In the past, doctors heavily over-prescribed antibiotics. Often as a precaution. The government and health providers have become very aware of an upcoming problem with high restistance though, so they are working hard to change the behaviour.
Existing doctors are re-educated not to prescribe Antibiotics on a hunch, with monitoring and reprimands from health providers.
And this is also drilled into med students in University.
Change always takes time... let's hope we won't be too late to avoid a serious increase in fatalities.
Antibiotics are heavily regulated and monitored in beef and dairy production in the EU to avoid food chain containment and the issues raised in the article. TTIP in the EU and Brexit in the UK will probably change that position for the worse.
No, they fucking aren't, especially when it comes to medicine. Antibiotics should be controlled like opiates; at least over-prescription of opiates doesn't endanger the whole species.
> What surprises me is with the levels of litigation against doctors, this hasn't seemed to trigger any change in behaviour.
Try fines - that's supposedly solved the opiate abuse problem.
I remember one businessman being interviewed who stated very clearly that the customer is not always right, but that the customer does have the right to be heard. I think that was a much better phrasing - and truer to the actual spirit of the original than what it means at face value.
In general antibiotic resistance is lost when it doesn't confer an advantage. In some cases resistance to antibiotics costs cells energy they'd much rather be spending on other things. When the antibiotic is gone, cells without the energy tax can outcompete ones that do and divide quicker. The population then reverts to sensitive cells again.
Even in a hypothetical case where a random enzyme mutation confers resistance with no real obvious cost or side effect to the cell, unless there is specific environmental pressure to keep that mutation, it can easily revert in subsequent generations.
Bacteria aren't resistant to a drug. They're resistant to a mechanism of action. For example, bacteria develop beta-lactamase based resistance, which can make them resistant to all beta-lactam antibiotics, which is any antibiotic with -illin in the name.
You'd potentially have to take whole classes of antibiotics out of circulation, for a long time. And even then, some of them will maintain resistance genes because these compounds are present in the environment.
> The economics of drug development are partly to blame.
> To offset the millions of dollars they pour into research, clinical trials and the FDA approval process, pharmaceutical companies aim to develop blockbuster drugs, said Dr. Anthony Fauci, director of the National Institute for Allergies and Infectious Diseases. An ideal candidate would be used by millions of people every day for the rest of their lives, like pills to keep cholesterol or blood pressure in check.
> Antibiotics won’t pay the freight. They should be prescribed sparingly and only used for about a week.
Hmmm. Natural selection of humans, in an environment partly controlled by Pharma.
Pharma needs lots of patients that consume a drug every day for life. (I take three of them, plus an arguable fourth.) People who take one or more of these drugs are valuable. Such people who live longer lives are more valuable.
By not discovering low revenue new antibiotics and making them available, what we're left with is people who take daily drugs for life, and somehow survive or avoid bacterial infection.
I want to believe that no one in Pharma has thought of this.
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[ 3.6 ms ] story [ 184 ms ] threadThe current free market approach is completely failing this. It's not particularly profitable to invest many years in a drug people only need to take once to cure a disease when compared to developing a drug people need to take for 5-10+ years to manage a disease.
Phage therapy should be further developed as well, which has been proven to work against some resistant strains.
Why couldn't their payment scheme be identical even if it's a one time dose? Instead of $1000 per year for a drug you need to buy every year for ten years, make it so it has an up front cost of $12,000 or whatever with a ten year payment plan available for people who don't have that kind of cash on hand. This suggestion obviously inspired by the real world good that is a one time purchase that people make all the time: houses.
But to elaborate, aside from the obvious ethical implications, there are also practical differences. You are usually not forced out-of-the-blue to buy a house, no matter if you can afford it or have just bought a house last month. Also, houses can be sold, so people have ways to back out of a purchase when they realize they cannot pay back the loan. None of this works for drugs.
Trying to apply the same logic to drugs would make the the debt problem of medical bills even worse than it already is. It would also lead to a strong inequality in medical care.
The problem with that approach is the way that hospitals are reimbursed for antibiotics in the US. There is no room for those prices. I know Congress is trying to change that by making antibiotics separately reimbursed.
[Source: I worked at a biotech firm that has a number of antibiotics in development]
Teixobactin is 2015 and is probably a member of a new class of antibiotics.
Also note that retrospective studies have shown that first observed resistance to an antibiotic appears about six months after it is introduced. We are producing new antibiotic families far slower than this rate.
What is not mentioned is a new class of antibiotics discovered in 2015 (https://en.wikipedia.org/wiki/Teixobactin) which is a big deal in that it can be used instead of antibiotics resistance to which has been acquired by bacteria during this "golden age" and as microbes evolve extremely fast, within an observable timeframe they will lose resistance to the old classes allowing those to be used again. So effectively shelving will work.
Another point is that other new methods of searching for new drugs are being researched (http://www.theverge.com/2016/5/18/11686268/new-antibiotic-dr...) and the future is not at all gloomy.
The funding purse is open for antibiotic research and I find it hard to believe its a dry well. I think we'll see more discoveries like these in our lifetime.
I absolutely agree that it won't be as gloomy as outlined in the article. The search for novel antibiotics has been pretty much neglected (Teixobactin is more of an exception to the rule) because the currently employed drugs work quite well. As this is changing, the possible market for novel antibiotics will increase and thus funding will shift into this direction.
[0] http://www.radiolab.org/story/best-medicine/
Ideally you have enough different classes of antibiotics that you can maintain a constant rotation and always have new antibiotics coming off shelved status so you can retire antibiotics that've formed resistances. Even better, a larger library of antibiotics directly improves the effectiveness of this strategy - in the short term, introducing a new class means you can shelve an old, resisted class; in the long term, more classes means each class can spend longer on the shelf and we reduce antibiotic resistance further.
"Strains of bacterial pathogens that have acquired mutations conferring antibiotic resistance often have a lower growth rate and are less invasive or transmissible initially than their susceptible counterparts." http://aac.asm.org/content/54/5/2085.full
If evolutionary logic holds (and there's little doubt about that, though research on the rate of resistance lose with time varies), switching to new classes of antibiotics and not using old ones until resistance to them de-evolves is a viable strategy.
Too long. You can get significant mileage out of a 3 year ban but resistance will return very quickly afterwards. You'd need to wait decades to truly reset the clock.
> After three years of banning the use of that antibiotic, the resistance of the bacteria dropped significantly. But because there were resisitant strains that persisted right through the end of the study in 2008, it was likely that the resistance would surge once again if the antibiotic were reintroduced. To safely reintroduce the antibiotic, Townsend said, you have to kill off all the pathogens.
> Considering how important antibiotics have become to human health — from the treatment of strep throat to MRSA to tuberculosis — Townsend says a 45-year ban on most antibiotics would be impractical. Doctors estimate it takes about that long for the resistance to disappear.
The problem is China loves to pump their livestock full of it to boost production, and now we're starting to see bacteria strains that are resistant to it.
http://phenomena.nationalgeographic.com/2015/11/21/mcr-gene-...
The WHO simply do not have any teeth to enforce shelving, and it's probably going to take a major health crisis before it's even on the table.
The use of common antibiotics isn't good, by any means, but last-defense drugs being used is far worse.
At least two cases have been detected in the US, the first was earlier this year, the second as of yesterday.
https://www.sciencedaily.com/releases/2016/07/160711150939.h...
As mentioned in the article, the colistin resistance is being transmitted via plasmid, so it is capable of diffusing quite widely into different types of bacteria.
Sure, new methods of finding antibiotics are in the works, although the article you link has plenty of experts recommending caution about their potential. The bigger point is that in 2016 there is a looooooong road from antibiotic "candidate" to FDA-approved drug. That road involves decades of trials and costs billions of dollars per approved drug.
The larger problem is that there is little if any incentive for pharma companies to invest in antibiotics compared to traditional blockbuster drugs that are supposed to be taken chronically (and therefore have better ROI). It's the same reason little R&D goes into making new vaccines. It doesn't matter how many candidates are found if they can't make it to market in a timely fashion (the point of the CDC bar graph), and this is what the "slow catastrophe" really is. It is not that scientists will never figure out new ways to kill bacteria.
Only because we've had time as a luxury in the past. I imagine new variants will get fast tracked. FDA bureaucrats hoping to lazy their way to retirement will be under a lot of pressure to actually get things done quickly when there's so much social need. No one wants to be the POTUS who didn't fast track life saving antibiotics if they're shown to be generally safe in early testing. The FDA is a government organization and as such is subject to the politics of our leadership and indirectly, the electorate.
The FDA has a page about this process here:
http://www.fda.gov/forpatients/approvals/fast/ucm20041766.ht...
At least 774 drugs have gone this route:
http://www.bmj.com/content/351/bmj.h4633
[1] http://jac.oxfordjournals.org/content/53/1/28.full
See also: https://en.wikipedia.org/wiki/Totalitarianism
Basically. Humans are horrible at cost/benefit calculations on an abstract level that may not directly affect them for years or even ever on an individual scale. I've known people who won't wear seatbelts because someone they know got trapped by one in a freak accident, despite overwhelming statistical evidence that's a dumb approach. The industry also has a long history of fighting regulations that require safety features but make cars more expensive.
http://www.nytimes.com/1986/07/20/weekinreview/the-give-and-...
> Last month, Ford proposed weakening the transportation department's 1984 rule in exchange for faster introduction of air bags in its cars. The company offered to install the bags on the driver's side of a majority of its cars by the 1990 model year if the department would drop its requirement that the front seats of all cars be equipped by then with automatic or so-called passive belts, designed to restrain the passenger as the car door closes.
http://blog.esurance.com/seat-belt-history/
> A Federal Motor Vehicle Safety Standard proposes that all vehicles made after January 1, 1973, include an automatic restraint system, i.e., air bags or automatic belts. The auto industry, knowing that it would have to increase production costs to meet the new standard, balks, leading to a decade of argument and delay.
https://en.wikipedia.org/wiki/Unsafe_at_Any_Speed
etc.
Judging from everybody I've seen texting while driving, NO, they don't.
You keep using this word, totalitarianism. I don't think it means what you think it means.
I mean, seat belt laws are totalitarian? That's kind of insulting to the victims of totalitarianism everywhere...
No, you should just avoid the slippery slope fallacy.
Antibiotics have already saved ~200 million lives, 80% of their use is in livestock, and they are of limited long term value. A reasonable guess is a Billion+ lives hang in the balance.
We convinced millions of people they'll feel better if they don't eat gluten. An entire cottage industry created. All without force. All without the influence of politics and fallible men.
How do you make the logical leap from "a big diet fad happened" to "the FDA is redundant and evil?"
And I can guarantee absolutely that purchasing power is not the be all end all, and that leaving it all to the free market and "if I want X, it's my choice" creates more issues than it solves. For example, nobody labelling what they sell as X (but as X+, the better variety), without legislation to prevent them.
And the same argument goes to BS like avoiding vaccination and people teaching Creative Design to their kids.
https://en.wikipedia.org/wiki/Snake_oil https://en.wikipedia.org/wiki/Medicine_show https://en.wikipedia.org/wiki/Patent_medicine
Just like Bitcoiners rediscovered the reasons our financial system has the various moving parts it does, healthcare regulations tend to have good reasons behind them.
Would you like some Thalidomide with that?
Oh! You never had a chance to get that in the US.
(For those who don't know her: https://en.wikipedia.org/wiki/Frances_Oldham_Kelsey was the filthy lazy bureaucrat we all wish we could be (i. e. heroic))
The Thalidomide argument points out the benefit: These regulations avoid releasing medications with bad side effects to the population. Nobody denies this is a good thing.
The costs are more rarely discussed. I think these are the main ones
1. When approval of a medication is delayed 10 years, everyone who would have been cured/helped by it during that time pays. Often with their life.
2. The high cost of FDA level trials makes medication more expensive. It also makes some medications economically unviable, with similar costs as in 1.
I'm not aware of any study trying to quantify these effects, but my wild guess/gut feel is that the costs are ~100 times bigger than the benefits.
The PR problem is that victims of bad medications are seen. The Thalidomide sufferers became world famous. But the ~100k Americans who died while the FDA took 17 years extra to approve beta blockers had no idea why they died.
We're still basically following the process established in 192x (Bayer, sulfa drugs) of throwing any structure we can think of onto some essay, into some mice, then humans. Educated guesses have become more educated, but not much better.
Regulation has only become a burden because we're chasing ever-decreasing improvements. Even placebo got better over the last decades, which may have doomed a few potential blockbusters.
It's obviously a problem of the lower-hanging fruits having been picked, and not all is bleak (kicking HIVs butt these days). But a cell just happens to be 35mill lines of self-modifying, multi-layered, self-evaluating, quantum-effects-using complexity and we're far away from a rational, hypothesis-driven drug discovery process.
Deregulation wouldn't actually help. While it is possibly attractive for a patient now, that comes at a certain and significant disadvantage for future patients: If you could sell everything you wanted, there'd be no incentive for studying efficacies – it'd just be random stuff that may work, competing in a dysfunctional marketplace.
Dysfunctional because nobody would know anything. Even with the somewhat professional studies we have today, and even for professionals, it is a major undertaking to form a solid opinion on a drug. Throw in patients who have nothing to lose and it'd probably be worse than it ever was.
It's not like experimental treatments aren't available today. Almost every cancer patient is enrolled in one or more trials, unless she immediately responds to existing drugs. Quite a few people have traveled to Asia for some stem cell snake oil (less money, nice tan, no improvement, life-threatening complications being the usual outcome).
There were 17 "thalidomide babies" born in the US.
The FDA also has a long history of whistleblowers to fight FDA corruption. Drugs like Avandia and Rezulin should give you pause.
Yes, lazy bureaucrats, rubber stamping, politics, and monied interests work together to make FDA approval a crap shoot. I never understood this whole "worship the state" aspect millennials subscribe to. The state has its own agenda and its usually counter to yours.
I have read all your comments -- including the doozy "all...without fallible men" -- and I will suggest that:
A) If you are incredibly savvy, you can already sidestep government regulation by pursuing remedies outside the scope of what they control.
B) Most people are not that savvy and, unfortunately, need the protection provided by government regulation.
C) There is zero means to remove the fallibility of "men" from the equation. (I am a woman. As much as I would love to joke that things would be so much better if women ruled the world, the reality is that the fallibility of humankind is inescapable. Also -- cough -- Theranos.)
D) Antibiotic resistance is not due to lazy bureaucrats. It is due to lazy humans. It's lazy humans all the way down. They are hardly confined to government.
E) Even in alternative med circles, you get social pressure and people with a profit motive and conflict of interest and on and on.
F) The path to solve this will never catch on. It is too much work. It can be done now. The research into how to break up biofilms is already at a useful stage, if you are sufficiently motivated.
G) Gosh, I wish you would step away from this discussion. You aren't adding any value here.
I used to joke that there were so many groups with a Gram+ antibiotic drug discovery program going that my parents were probably running one out of their cellar.
Gram- are tough.
For example, fluoroquinolones can kill both Gram+ and Gram- microbes, but they are generally better at killing Gram-.
Other classes have the reverse characteristics.
I don't know much about the types of microbes that cause periodontal disease.
However, my company was initially interested in treating Community Acquired Pneumonia (CAP). The problem with CAP (and many other bacterial infections) is that they can be caused by either Gram+ or Gram- pathogens. This means that if you're making a drug to treat CAP, you need an antibiotic that can "hit" both types.
A common occurrence when we were looking for a candidate drug that could treat CAP was that the candidate would be powerful at killing Gram+ CAP microbes and weak at killing Gram- CAP species. If we improved the drug's ability to "hit" Gram- species, we would always seem to lose potency against Gram+. It was extremely tricky to find something that was powerful enough against _all_ the relevant microbial pathogens.
That's freaking fascinating, I'm in bioinformatics myself, I'd love to hear more about this- I wasn't aware that an antibiotic discovery startup was/is/could be a thing at all- If you can tell me anything more or put me on the right track to reading more about your old employer in that space or whatnot, I'd appreciate it! :)
But these startups do exist: look up Achaogen (achaogen.com) and Tetraphase (tphase.com).
Cubist Pharmaceuticals was a big antibiotic developer that was recently purchased by Merck. Cubist itself bought another startup called Trius Pharmaceuticals, which had developed a newly marketed antibiotic.
So, there is $$ to be made in antibiotic drug development, but as many people on this thread have pointed out, there is more $$$$ to be made in other therapeutic areas (e.g., oncology).
[1] https://en.wikipedia.org/wiki/Fidaxomicin
My crazy theory is that somebody with drug resistant TB could be deliberately infected with regular TB, which will replace all the DR TB, and then you treat the patient normally. Assuming they survive.
Call us when any of them survive the valley of death that kills 99%+ of substances with interesting in vitro activity to reach clinical use and the hypothetical becomes actual. In the mean time, real people are dying real deaths.
Might be a bit rough on gut bacteria, though...
From what I have read and experienced firsthand, you are far better off strengthening your gut flora, not undermining them.
> Artificially constructed plasmids may be used as vectors in genetic engineering. These plasmids serve as important tools in genetics and biotechnology labs, where they are commonly used to clone and amplify (make many copies of) or express particular genes.[12] A wide variety of plasmids are commercially available for such uses. The gene to be replicated is normally inserted into a plasmid that typically contains a number of features for their use. These include a gene that confers resistance to particular antibiotics (ampicillin is most frequently used for bacterial strains), an origin of replication to allow the bacterial cells to replicate the plasmid DNA, and a suitable site for cloning.
I think that the problem would be coming up with a delivery method.
We already know. There are four main mechanisms for horizontal gene transfer:
1. Free DNA uptake 2. Phage transfer 3. Conjugation 4. GTA
Preventing any of these is near impossible.
We have however had some success in using phage therapy against some MDRs.
There is probably a huge array of such things out there. They are unlikely to be as broad-spectrum as traditional antibiotics, but with research we should be able to find ones to apply to the right situations.
At the same time as this crisis unfolds, our ability to know exactly what someone is infected with improves. Soon sequencing of bacterial infections will be the first step in patient triage. This will help us apply precisely the right toxin to rid the body of the problematic type(s) of bacteria.
https://en.wikipedia.org/wiki/Phage_therapy
- There is no such thing as a "broad spectrum" phage. You can't do empirical treatment using phages, and there's not really "off the shelf" phage therapy - it tends to be a bespoke creation for a particular infection.
- There's some serious regulatory problems, similar to those experienced by fecal transplant treatments. We're not yet really equipped to think about handling evolving, custom microbes as a treatment.
- Because of the first, it's going to require a considerable amount more lab capacity than most clinical settings currently have, and considerable delays until treatment.
- There's also some biosafety issues around phage prep, but those are easily solvable.
It's a great way to treat particularly resistant or hard to treat infections, but it's not a particularly great general solution. There's a reason it was abandoned in countries with easy access to antibiotics - they're just roundly superior in basically every respect.
It's nice to get paid to solve a problem you created in the first place.
http://jac.oxfordjournals.org/content/70/8/2177.full
My experience with kids is that here in Spain they are using older antibiotics now to preserve the newer ones for serious infections trying to limit evolutionary pressure on the bacteria.
1) farmers everywhere are allowed to use last line/new antibiotics routinely in food production. This is utterly fucking stupid. Whats more brain dead is that its not just china its US and canada. (possibly the EU.) It could be stopped by the FDA withdrawing the license. but no. Too much money.
2) over subscription in private health.
I once listened to a co-worker phone up the Doctor and ask to have "the same antibiotics I had last time for that cold" and get it[1]. She had the fucking snuffles. No consultation, not even bothering to figure out if its even got a hint of bacterial infection.
A placebo would have been more effective. It wouldn't have given her the shits either. Paracetamol is what was needed, as its the only thing that would have made her feel better.
Seriously. yes I know that the customer is always right, but don't fucking dish out drugs like sweets. My old age, and my children's health are dependent on those drugs.
[1] yes this was in the USA, santa monica to be precise. Yes I'm british. However the prevalence of prescription medication abuse and deaths is a massive fucking warning. Something is horridly wrong with the US's health care system.
What surprises me is with the levels of litigation against doctors, this hasn't seemed to trigger any change in behaviour.
Disclosure: I live with a doctor.
Basically, it's exactly the worst thing you can possibly do, with regards to what the theory of evolution by natural selection tells us. Then add in what we know about bacteria exchanging genetic material, and it's like we're trying to inactivate all of our antibiotics on purpose.
from the half-full glass POV we are just speeding up the natural selection of bacteria resistant humans (it has been going for millenia and got, probably only temporary, delayed for the last 80 years). Also, as a side effect, it can help solve (at least temporarily) the overpopulation issue until the much more smart (wrt. health and Earth resources usage) humans evolve. Basic dialectics at work.
Often, what's good for species evolution is really bad for some individuals. What good is a half-full glass to you if you're dead?
Also, as was noted elsewhere in the discussions, evolutionary pressure for bacteria to attain an immunity is high, but pressure to lose one is usually much lower. However, bacteria are small, and such pressure is higher than in more complex celled creatures. "Shelving" antibiotics does work, but would require widespread cooperation and the curbing of feeding antibiotics to livestock.
What bad is it if you're dead?
Bahaha that's one way to look at it. I guess we have plenty of humans to spare.
Bacteria evolves resistance at about the same rate as people develop defenses.
So yeah, if you don't mind killing off a huge segment of the population and having women die in childbirth regularly.
Disclosure: I live with a doctor.
Irrelevant aside: Rare to find someone on HN call a disclosure a disclosure, rather than the oft-abused "disclaimer"! :)
The _crux_ of the issue is that doctors prescribe antibiotics for viral infections because the diagnosis is usually only based on a cursory examination. Their time is expensive, and you can't spend an hour on every patient with a cough and a fever. Furthermore, viral infections often precede or are concurrent with bacterial infections. So doctors are making a rational decision when prescribing antibiotics, and it's not even clear that this decision is globally suboptimal because bacterial infections are not uncommon with a cold or especially a flu.
If we're serious about overprescription of antibiotics, we should be heavily investing in improved diagnostic equipment and processes. For example, rapidly scanning mucus samples for viral and bacterial markers. The fact that we don't appear to be doing this suggests that either overprescription isn't actually a problem, or that we're not thinking seriously about the problem.
In the past, doctors heavily over-prescribed antibiotics. Often as a precaution. The government and health providers have become very aware of an upcoming problem with high restistance though, so they are working hard to change the behaviour.
Existing doctors are re-educated not to prescribe Antibiotics on a hunch, with monitoring and reprimands from health providers.
And this is also drilled into med students in University.
Change always takes time... let's hope we won't be too late to avoid a serious increase in fatalities.
No, they fucking aren't, especially when it comes to medicine. Antibiotics should be controlled like opiates; at least over-prescription of opiates doesn't endanger the whole species.
> What surprises me is with the levels of litigation against doctors, this hasn't seemed to trigger any change in behaviour.
Try fines - that's supposedly solved the opiate abuse problem.
Even in a hypothetical case where a random enzyme mutation confers resistance with no real obvious cost or side effect to the cell, unless there is specific environmental pressure to keep that mutation, it can easily revert in subsequent generations.
You'd potentially have to take whole classes of antibiotics out of circulation, for a long time. And even then, some of them will maintain resistance genes because these compounds are present in the environment.
> To offset the millions of dollars they pour into research, clinical trials and the FDA approval process, pharmaceutical companies aim to develop blockbuster drugs, said Dr. Anthony Fauci, director of the National Institute for Allergies and Infectious Diseases. An ideal candidate would be used by millions of people every day for the rest of their lives, like pills to keep cholesterol or blood pressure in check.
> Antibiotics won’t pay the freight. They should be prescribed sparingly and only used for about a week.
Hmmm. Natural selection of humans, in an environment partly controlled by Pharma.
Pharma needs lots of patients that consume a drug every day for life. (I take three of them, plus an arguable fourth.) People who take one or more of these drugs are valuable. Such people who live longer lives are more valuable.
By not discovering low revenue new antibiotics and making them available, what we're left with is people who take daily drugs for life, and somehow survive or avoid bacterial infection.
I want to believe that no one in Pharma has thought of this.