7 ms·

They author's state "it should be used, if it gets successfully developed, as broadly as possible" - because they believe it is robust against bacteria developi

They author's state "it should be used, if it gets successfully developed, as broadly as possible" - because they believe it is robust against bacteria developing resistance. Knowing nothing about this area... isn't this a bad idea because board use would increase the risk of resistance appearing and would mean those bacteria resistant to this would be extremely resistant to most other treatments aw well (given this drug has multiple modes of attack)?

onezeno 12y ago
That was the statement by the guy trying to develop and sell it.
balabaster 12y ago
Yeah, that was my first reaction too... Surely only using it in cases where other antibiotics hadn't proven successful would be a better approach so that you don't give bacteria much opportunity to become resistant. Broad use of antibiotics in cases where it wasn't needed is exactly how we got into this problem in the first place. Perhaps learning from history would be the most prudent approach.
- learc83 12y ago
  Antibiotic resistance has a fitness penalty. If we switch to this new antibiotic for long enough, bacteria may lose their resistance to our current antibiotics. I'm assuming their suggestion is to use this drug for the next 30 years, and by the time bacteria become resistant to it we can start using our old antibiotics again.
  - Fomite 12y ago
    Antibiotic resistance does not necessarily have a strong fitness penalty - the spread of community-resistant MRSA is largely in environments where there isn't strong selective pressure against susceptible strains.
- tezza 12y ago
  I think some in depth academic research would be required to determine the optimal strategy. Intuitive strategies may not be as good as some counter-intuitive options. I'm not qualified to answer either way, I imagine several people could get PhDs finding out. It's too important to handle quickly
mseebach 12y ago
Apparently they have a very plausible reason to think it will be robust: It attacks cell walls, which are structural, rather than receptors (I think I'm using the term correctly) that are proteins and prone to mutations. It's basically the same reason we don't fear bacteria to develop resistance to boiling or alcohol disinfectant.
- gus_massa 12y ago
  I tempted to write "What could go wrong?" or "Life finds a way.". A fast Google search gives this paper: " Relatively Alcohol-Resistant Mycobacteria Are Emerging Pathogens in Patients Receiving Acupuncture Treatment" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC140401/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC140401/ There are some archeas (and a few bacterias) that support boiling temperature, but IIRC they don't like meatware because it's too cold for them. http://en.wikipedia.org/wiki/Hyperthermophile http://en.wikipedia.org/wiki/Hyperthermophile
  - jobu 12y ago
    > I tempted to write "What could go wrong?" or "Life finds a way.". My thoughts exactly. Try using it in large scale animal farms for a couple decades and I'm betting something will become resistant.
    - platz 12y ago
      I thought some bacteria had developed double walls with an insulating fluid, so that they could expunge bad chemicals.
  - erroneousfunk 12y ago
    I did a project on mycobacteria in college, and its not surprising that some of these are resistant to alcohol. These are bacteria that produce a hard protein shell that protect colonies of bacteria, and they can be difficult to attack or scrub off. Mycobacterium Abscessus, in particular is great at surviving in low-carbon environments (with very little food), and its protective shell and clustering formation protects it from low levels of chlorine. I cultured shower heads, sink faucets, and soda fountains in order to find them. Nasty stuff.
jonknee 12y ago
I think the idea behind that is it would prevent further resistance building against existing drugs.
- rjurney 12y ago
  Yes. If it takes 30 years for this drug to become resistant, but 5 or 10 for other antibiotics... then a sound strategy is to use the long-lasting drug, and save the drugs with a shorter lifespan as second, or third tier. This will slow the development of resistance, so they will last longer, and we'll have a broader range of working antibiotics at any given time. Which means more infections successfully treated, and more lives saved. Win!
  - electromagnetic 12y ago
    If we eliminated treatment with drugs with resistances against them, we'd no longer be artificially selecting for those bacteria, which would mean the bacteria that naturally performed better would be the most likely to survive. Essentially if we stop treating with the drugs with resistances against them, we'd eventually end up with a bacteria gene pool that resembled the original pre-resistant one, where resistant bacteria were replication errors that were drowned out by natural selection. The only issue is we can't do that without sacrificing millions of lives. So having a drug that works via completely different mechanisms would fulfil both.
    - philwelch 12y ago
      This is exactly what we've been doing for decades. When you get an antibiotic-resistant infection, like I have twice, they just give you older antibiotics. So the more antibiotics you have, the better, because it's harder for a bacteria to be resistant to more and more antibiotics at once.
      - rjurney 12y ago
        Well, they give you more toxic antibiotics that may be older but that have too many side effects for routine use.
refurb 12y ago
If this actually did get to market, it wouldn't be used broadly. Doctors and hospital already follow antibiotic stewardship policies that would limit drugs like this last-line uses.
- gaius 12y ago
  But they don't tho', that's why there's a problem. GPs hand out antibiotics like candy.
  - refurb 12y ago
    Sure, they hand out the antibiotics where resistance has already developed, but trust me, the "last ditch effort" antibiotics (like vancomycin) don't get used broadly at all.
    - mv 12y ago
      Vancomycin is used routinely (at least in the three hospitals I work in) and it is far from a last ditch drug. That has shifted to Linezolid and Daptomcyin. In the three hospitals I work at, medicine doctors must consult Infectious Disease doctors for approval to place patients on those therapies.
      - refurb 12y ago
        "Last ditch" is a poor choice of words. The point I was trying to make is that if you come to you doc with the sniffles, it's unlikely you're going to get an Rx for vancomycin.
      - Fomite 12y ago
        The parent post was referring to GPs, which at least in the U.S. aren't often operating in hospitals, and certainly don't get ID consults. Vancomycin is the drug of choice for several major infections that are of a concern to hospitals (MRSA, C. difficile) because there's already pretty established resistance mechanisms. There are definitely some "more last ditch" drugs, but Vancomycin is kind of the first of the "Now we bring out the big guns" antibiotics. Partially because it's a PITA to give to patients, and has some toxicity problems.
angersock 12y ago
That's kind of the perverse incentive here, right? To recoup your costs, you need to sell as much as possible--but in doing so, you render your own product obsolete due to continuing counter-evolution by the target species.
- Fomite 12y ago
  Which is why one of the suggestions for improving antibiotic development is to heavily subsidize it - working antibiotics are a public good, and if you remove the need to sell drugs in order to pay for their development, you remove the incentive to use them too widely.
electromagnetic 12y ago
If it has the same relative safety of use as penicillin lines of antibiotics, but is more robust in its method of action to prevent resistance occurring as easily, then my guess would be it would be preferable to use as widely as possible. The idea is that drug resistance comes with a metabolic cost. We're making them do something to survive that we didn't before, and it's going to come at a cost. If we think of them like cars--armoured ones are extremely rare. However, if we started randomly shooting at cars, and did so for a protracted period, we would eventually see them become more common. The fact they're slower, don't turn as well, and use more fuel is now negligible because of the excessive benefit of it's contents not being shredded. If the implementation of this new antibiotic came with a moratorium on the prescription of penicillin, then we would be targeting the population as a whole with an RPG. It doesn't matter if you're armoured against bullets anymore. Both the normal and the resistant will be put under the identical survival pressures, which should mean it is more effective against the resistant strains as these won't be as fast to replicate. The problem from what I understand is that tackling antibiotic resistant drugs with drugs designed for antibiotic bacteria, just makes super bugs. Essentially if we cleared the roads of regular cars and left ourselves with armoured cars, and then start firing RPGs at them, we'll end up with vehicles resistant to those. We will end up with APC's on the road. If we implemented a moratorium on penicillin strain antibiotics, we could potentially reverse the current epidemic of multi-drug resistant strains. It would be like starting anew - assuming there's no genes that are equally beneficial against both drugs. That's my understanding of the reasoning behind suggesting broad use, but I could be way off.
- kale 12y ago
  That seems to be a reasonable thought, although incredibly difficult to prove. Primates and guinea pigs both dropped the ability to synthesize Vitamin C, through different mutations. Now both species have to consume it in their diet to survive. Incidentally, the story of the broken Vitamin C gene in primates and guinea pigs is the main argument that gets used to show how the theory of evolution is supported. In all primates, including humans, the gene to make Vitamin C is in our DNA, but mutated so that it is not usable. But all primates have the mutated gene in the same place. Guinea pigs have a different mutation to the gene. The chance that all primates had the mutation in the same location simultaneously is very remote, suggesting all primates shared an ancestor that developed the mutation.
soperj 12y ago
In the "TheScientist" article, they say the exact opposite. Maybe it's a misquote?
philwelch 12y ago
I wouldn't do something stupid like give it to every single head of livestock in the world (cough) but the great thing about antibiotic-resistant bacteria is that they're not resistant to all antibiotics at once. Without the evolutionary pressure to stay resistant to antibiotic B, a bacteria can be resistant to antibiotic A but not so much A and B at the same time. (Which is why things like MRSA are treated with very old and unpopular antibiotics). Any new antibiotic makes this approach even better, because if you have A, B, C, D, and now E, now the bacteria has to be resistant to all five at once, which is a lot of useless genes to hold onto.

onezeno 12y ago

That was the statement by the guy trying to develop and sell it.

balabaster 12y ago

Yeah, that was my first reaction too... Surely only using it in cases where other antibiotics hadn't proven successful would be a better approach so that you don't give bacteria much opportunity to become resistant. Broad use of antibiotics in cases where it wasn't needed is exactly how we got into this problem in the first place. Perhaps learning from history would be the most prudent approach.

learc83 12y ago
Antibiotic resistance has a fitness penalty. If we switch to this new antibiotic for long enough, bacteria may lose their resistance to our current antibiotics. I'm assuming their suggestion is to use this drug for the next 30 years, and by the time bacteria become resistant to it we can start using our old antibiotics again.
- Fomite 12y ago
  Antibiotic resistance does not necessarily have a strong fitness penalty - the spread of community-resistant MRSA is largely in environments where there isn't strong selective pressure against susceptible strains.
tezza 12y ago
I think some in depth academic research would be required to determine the optimal strategy. Intuitive strategies may not be as good as some counter-intuitive options. I'm not qualified to answer either way, I imagine several people could get PhDs finding out. It's too important to handle quickly

mseebach 12y ago

Apparently they have a very plausible reason to think it will be robust: It attacks cell walls, which are structural, rather than receptors (I think I'm using the term correctly) that are proteins and prone to mutations. It's basically the same reason we don't fear bacteria to develop resistance to boiling or alcohol disinfectant.

gus_massa 12y ago
I tempted to write "What could go wrong?" or "Life finds a way.". A fast Google search gives this paper: " Relatively Alcohol-Resistant Mycobacteria Are Emerging Pathogens in Patients Receiving Acupuncture Treatment" http://www.ncbi.nlm.nih.gov/pmc/articles/PMC140401/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC140401/ There are some archeas (and a few bacterias) that support boiling temperature, but IIRC they don't like meatware because it's too cold for them. http://en.wikipedia.org/wiki/Hyperthermophile http://en.wikipedia.org/wiki/Hyperthermophile
- jobu 12y ago
  > I tempted to write "What could go wrong?" or "Life finds a way.". My thoughts exactly. Try using it in large scale animal farms for a couple decades and I'm betting something will become resistant.
  - platz 12y ago
    I thought some bacteria had developed double walls with an insulating fluid, so that they could expunge bad chemicals.
- erroneousfunk 12y ago
  I did a project on mycobacteria in college, and its not surprising that some of these are resistant to alcohol. These are bacteria that produce a hard protein shell that protect colonies of bacteria, and they can be difficult to attack or scrub off. Mycobacterium Abscessus, in particular is great at surviving in low-carbon environments (with very little food), and its protective shell and clustering formation protects it from low levels of chlorine. I cultured shower heads, sink faucets, and soda fountains in order to find them. Nasty stuff.

jonknee 12y ago

I think the idea behind that is it would prevent further resistance building against existing drugs.

rjurney 12y ago
Yes. If it takes 30 years for this drug to become resistant, but 5 or 10 for other antibiotics... then a sound strategy is to use the long-lasting drug, and save the drugs with a shorter lifespan as second, or third tier. This will slow the development of resistance, so they will last longer, and we'll have a broader range of working antibiotics at any given time. Which means more infections successfully treated, and more lives saved. Win!
- electromagnetic 12y ago
  If we eliminated treatment with drugs with resistances against them, we'd no longer be artificially selecting for those bacteria, which would mean the bacteria that naturally performed better would be the most likely to survive. Essentially if we stop treating with the drugs with resistances against them, we'd eventually end up with a bacteria gene pool that resembled the original pre-resistant one, where resistant bacteria were replication errors that were drowned out by natural selection. The only issue is we can't do that without sacrificing millions of lives. So having a drug that works via completely different mechanisms would fulfil both.
  - philwelch 12y ago
    This is exactly what we've been doing for decades. When you get an antibiotic-resistant infection, like I have twice, they just give you older antibiotics. So the more antibiotics you have, the better, because it's harder for a bacteria to be resistant to more and more antibiotics at once.
    - rjurney 12y ago
      Well, they give you more toxic antibiotics that may be older but that have too many side effects for routine use.

refurb 12y ago

If this actually did get to market, it wouldn't be used broadly. Doctors and hospital already follow antibiotic stewardship policies that would limit drugs like this last-line uses.

gaius 12y ago
But they don't tho', that's why there's a problem. GPs hand out antibiotics like candy.
- refurb 12y ago
  Sure, they hand out the antibiotics where resistance has already developed, but trust me, the "last ditch effort" antibiotics (like vancomycin) don't get used broadly at all.
  - mv 12y ago
    Vancomycin is used routinely (at least in the three hospitals I work in) and it is far from a last ditch drug. That has shifted to Linezolid and Daptomcyin. In the three hospitals I work at, medicine doctors must consult Infectious Disease doctors for approval to place patients on those therapies.
    - refurb 12y ago
      "Last ditch" is a poor choice of words. The point I was trying to make is that if you come to you doc with the sniffles, it's unlikely you're going to get an Rx for vancomycin.
    - Fomite 12y ago
      The parent post was referring to GPs, which at least in the U.S. aren't often operating in hospitals, and certainly don't get ID consults. Vancomycin is the drug of choice for several major infections that are of a concern to hospitals (MRSA, C. difficile) because there's already pretty established resistance mechanisms. There are definitely some "more last ditch" drugs, but Vancomycin is kind of the first of the "Now we bring out the big guns" antibiotics. Partially because it's a PITA to give to patients, and has some toxicity problems.

angersock 12y ago

That's kind of the perverse incentive here, right? To recoup your costs, you need to sell as much as possible--but in doing so, you render your own product obsolete due to continuing counter-evolution by the target species.

Fomite 12y ago
Which is why one of the suggestions for improving antibiotic development is to heavily subsidize it - working antibiotics are a public good, and if you remove the need to sell drugs in order to pay for their development, you remove the incentive to use them too widely.

electromagnetic 12y ago

If it has the same relative safety of use as penicillin lines of antibiotics, but is more robust in its method of action to prevent resistance occurring as easily, then my guess would be it would be preferable to use as widely as possible. The idea is that drug resistance comes with a metabolic cost. We're making them do something to survive that we didn't before, and it's going to come at a cost. If we think of them like cars--armoured ones are extremely rare. However, if we started randomly shooting at cars, and did so for a protracted period, we would eventually see them become more common. The fact they're slower, don't turn as well, and use more fuel is now negligible because of the excessive benefit of it's contents not being shredded. If the implementation of this new antibiotic came with a moratorium on the prescription of penicillin, then we would be targeting the population as a whole with an RPG. It doesn't matter if you're armoured against bullets anymore. Both the normal and the resistant will be put under the identical survival pressures, which should mean it is more effective against the resistant strains as these won't be as fast to replicate. The problem from what I understand is that tackling antibiotic resistant drugs with drugs designed for antibiotic bacteria, just makes super bugs. Essentially if we cleared the roads of regular cars and left ourselves with armoured cars, and then start firing RPGs at them, we'll end up with vehicles resistant to those. We will end up with APC's on the road. If we implemented a moratorium on penicillin strain antibiotics, we could potentially reverse the current epidemic of multi-drug resistant strains. It would be like starting anew - assuming there's no genes that are equally beneficial against both drugs. That's my understanding of the reasoning behind suggesting broad use, but I could be way off.

kale 12y ago
That seems to be a reasonable thought, although incredibly difficult to prove. Primates and guinea pigs both dropped the ability to synthesize Vitamin C, through different mutations. Now both species have to consume it in their diet to survive. Incidentally, the story of the broken Vitamin C gene in primates and guinea pigs is the main argument that gets used to show how the theory of evolution is supported. In all primates, including humans, the gene to make Vitamin C is in our DNA, but mutated so that it is not usable. But all primates have the mutated gene in the same place. Guinea pigs have a different mutation to the gene. The chance that all primates had the mutation in the same location simultaneously is very remote, suggesting all primates shared an ancestor that developed the mutation.

soperj 12y ago

In the "TheScientist" article, they say the exact opposite. Maybe it's a misquote?

philwelch 12y ago

I wouldn't do something stupid like give it to every single head of livestock in the world (cough) but the great thing about antibiotic-resistant bacteria is that they're not resistant to all antibiotics at once. Without the evolutionary pressure to stay resistant to antibiotic B, a bacteria can be resistant to antibiotic A but not so much A and B at the same time. (Which is why things like MRSA are treated with very old and unpopular antibiotics). Any new antibiotic makes this approach even better, because if you have A, B, C, D, and now E, now the bacteria has to be resistant to all five at once, which is a lot of useless genes to hold onto.