5 ms·

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 gl

by 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.
yourkin 10y ago
Bacteria are minimalist (http://www.sciencedirect.com/science/article/pii/S0092867402006657 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 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.
- aab0 10y ago
  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.
  - riffraff 10y ago
    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.
  - fweespeech 10y ago
    http://articles.courant.com/2011-01-11/health/hc-weir-antibiotic-yale-0112-20110111_1_antimicrobial-chemotherapy-antibiotics-edward-septimus http://articles.courant.com/2011-01-11/health/hc-weir-antibi... 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.

by folli 10y ago

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.

yourkin 10y ago

Bacteria are minimalist (http://www.sciencedirect.com/science/article/pii/S0092867402006657 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 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.

aab0 10y ago
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.
- riffraff 10y ago
  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.
- fweespeech 10y ago
  http://articles.courant.com/2011-01-11/health/hc-weir-antibiotic-yale-0112-20110111_1_antimicrobial-chemotherapy-antibiotics-edward-septimus http://articles.courant.com/2011-01-11/health/hc-weir-antibi... 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.