7 ms·

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://e

by yourkin 10y ago

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 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-drug-candidates-resistance-harvard-macrolide http://www.theverge.com/2016/5/18/11686268/new-antibiotic-dr...) and the future is not at all gloomy.

drzaiusapelord 10y ago
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.
- folli 10y ago
  It's probably more a case of "not looking hard enough", especially since this antibiotic class was discovered only ~1 year ago
folli 10y ago
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.
- lost_my_pwd 10y ago
  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. [0] http://www.radiolab.org/story/best-medicine/ http://www.radiolab.org/story/best-medicine/
- saulrh 10y ago
  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.
  - redblacktree 10y ago
    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.
    - yourkin 10y ago
      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.
deleted 10y ago
[deleted]
ansible 10y ago
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.
pak 10y ago
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.
- drzaiusapelord 10y ago
  >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. The FDA has a page about this process here: http://www.fda.gov/forpatients/approvals/fast/ucm20041766.htm 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 http://www.bmj.com/content/351/bmj.h4633
  - djschnei 10y ago
    Am I the only one that would prefer that politics and lazy bureaucrats didn't have the ability to get in the way of my well being in the first place?
tedunangst 10y ago
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.
aab0 10y ago
> 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.
guelo 10y ago
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.

by yourkin 10y ago

drzaiusapelord 10y ago

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.

folli 10y ago
It's probably more a case of "not looking hard enough", especially since this antibiotic class was discovered only ~1 year ago

folli 10y ago

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.

lost_my_pwd 10y ago
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. [0] http://www.radiolab.org/story/best-medicine/ http://www.radiolab.org/story/best-medicine/
saulrh 10y ago
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.
- redblacktree 10y ago
  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.
  - yourkin 10y ago
    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.

deleted 10y ago

[deleted]

ansible 10y ago

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.

pak 10y ago

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.

drzaiusapelord 10y ago
>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. The FDA has a page about this process here: http://www.fda.gov/forpatients/approvals/fast/ucm20041766.htm 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 http://www.bmj.com/content/351/bmj.h4633
- djschnei 10y ago
  Am I the only one that would prefer that politics and lazy bureaucrats didn't have the ability to get in the way of my well being in the first place?

tedunangst 10y ago

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.

aab0 10y ago

> 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.

guelo 10y ago

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.