New antibiotic kills off persistent infections(phenomena.nationalgeographic.com)
phenomena.nationalgeographic.com
New antibiotic kills off persistent infections
http://phenomena.nationalgeographic.com/2013/11/13/killing-sleeper-cells-and-superbugs-with-assassin-janitors/
15 comments
> isolated from the bacteria Streptomyces hawaiiensis in 1985 ... ADEP4 is one of those, and was reported in a paper published in 2005 ... [potential trials in coming years]
Gives an idea of the sort of development timescale we're talking about. It's almost 30 years from isolation to this point. Clinical trials would take another 10-15 years. So, if all goes well, that's 40 years from the initial discovery until a doctor starts making up prescriptions.
Gives an idea of the sort of development timescale we're talking about. It's almost 30 years from isolation to this point. Clinical trials would take another 10-15 years. So, if all goes well, that's 40 years from the initial discovery until a doctor starts making up prescriptions.
Excellent summary. I look forward to when our knowledge of cell biology is so complete that there isn't any time wasted on 'trying to understand its mechanism' rather we can explain such mechanism from first principles and know with certainly not only how it works, but how to adjust it to work most effectively to our benefit.
It's a peptide? Neat!
The most understated portion of the article is that there is a method discovered that can kill biofilms. The discovery of new antibiotics and delivery techniques leaves me less optimistic for long-term change in the availability of life-saving antibiotics. I suspect bacteria can, and will, evolve around almost any mitigating technique we develop.
Yet I'm optimistic, because tools that crack biofilms are a new are of development and promise hope for exploring new attacks on bacteria. Current methods of biofilm dispersal are application of strong acids and bases or an autoclave. You can't treat a hospital room with an autoclave, and comprehensive treatment of a room with very strongly ionizing agents has its own risks. There are other, experimental methods, but all are worth examining.
I hope research like this continues.
Yet I'm optimistic, because tools that crack biofilms are a new are of development and promise hope for exploring new attacks on bacteria. Current methods of biofilm dispersal are application of strong acids and bases or an autoclave. You can't treat a hospital room with an autoclave, and comprehensive treatment of a room with very strongly ionizing agents has its own risks. There are other, experimental methods, but all are worth examining.
I hope research like this continues.
"You can't treat a hospital room with an autoclave"
Hmmm... that sounds like an awfully good idea, actually...
Build the hospital room with the ability to be airtight, make sure all materials can withstand 134 C (or remove things that can't for their own cleaning) ... and autoclave the room ...
Hmmm... that sounds like an awfully good idea, actually...
Build the hospital room with the ability to be airtight, make sure all materials can withstand 134 C (or remove things that can't for their own cleaning) ... and autoclave the room ...
There are simpler things.
Like not having mega-hospitals that are impossible to keep entirely clean.
Growing up near the UCLA Medical Center, a vast, vast complex, I heard tales that there were diseases that existed there and nowhere else in the world. Most patients derive little benefit from the scale of the hospital and the fact that in a huge hospital getting all rooms clean at once is logistically very difficult means that scale can be very dangerous.
Like not having mega-hospitals that are impossible to keep entirely clean.
Growing up near the UCLA Medical Center, a vast, vast complex, I heard tales that there were diseases that existed there and nowhere else in the world. Most patients derive little benefit from the scale of the hospital and the fact that in a huge hospital getting all rooms clean at once is logistically very difficult means that scale can be very dangerous.
I'm...not sure I agree with most of this.
First of all, the size and scope of the hospital has very little to do with whether or not any particular room can be cleaned. The things that are "hard" to clean in rooms are features of the rooms themselves, not the number of them. For example, even small hospitals have TV remotes, soft and absorbent surfaces like mattresses, toilets, etc.
For that matter, small hospitals can't benefit from the economies of scale that allow large hospitals to have dedicated specialist cleaning teams for high risk rooms, or for that matter dedicated infection prevention staff.
First of all, the size and scope of the hospital has very little to do with whether or not any particular room can be cleaned. The things that are "hard" to clean in rooms are features of the rooms themselves, not the number of them. For example, even small hospitals have TV remotes, soft and absorbent surfaces like mattresses, toilets, etc.
For that matter, small hospitals can't benefit from the economies of scale that allow large hospitals to have dedicated specialist cleaning teams for high risk rooms, or for that matter dedicated infection prevention staff.
First of all, the size and scope of the hospital has very little to do with whether or not any particular room can be cleaned.
Uh, you're right but you're missing the implication. Scale influences whether every room can be clean simultaneously. A given room being dirty and infected with a bug adapted to surviving in a hospital lets said bug be tracked or blown to a different room before the bug is eliminated from the first room.
As for dedicated teams, I don't see why such things couldn't exist on a city-wide basis if they were useful.
The question whether healthcare benefits economies of scale at all is open to question. It clearly doesn't benefit too much given the lack of price differentials. The lousy and getting-lousier quality of American healthcare just generally indicates that hospitals don't put profits from economies of scale or whatever else back to real improvements in safety - though they apparent put a lot of money into meals to entice returning patients (fancy meals - visible, real safety - invisible).
Uh, you're right but you're missing the implication. Scale influences whether every room can be clean simultaneously. A given room being dirty and infected with a bug adapted to surviving in a hospital lets said bug be tracked or blown to a different room before the bug is eliminated from the first room.
As for dedicated teams, I don't see why such things couldn't exist on a city-wide basis if they were useful.
The question whether healthcare benefits economies of scale at all is open to question. It clearly doesn't benefit too much given the lack of price differentials. The lousy and getting-lousier quality of American healthcare just generally indicates that hospitals don't put profits from economies of scale or whatever else back to real improvements in safety - though they apparent put a lot of money into meals to entice returning patients (fancy meals - visible, real safety - invisible).
I'm not missing the implication, because rooms don't have to be clean simultaneously. Bacteria aren't actually all that mobile - most transmission is from touch contact with surfaces (or patients, who are themselves surfaces). Major disinfection takes place when a room is vacated, and it gets done - there's no reason to suggest that a cleaning staff doesn't scale with hospital size.
What's far more important is the quality of the room disinfection, which again, is a property of the room, not the number of them.
As for dedicated teams, I don't see why such things couldn't exist on a city-wide basis if they were useful.
Because now all you've done is taken the same workload, and said "Now you need to deal with 5 different smaller hospitals, five administration schemes (two of which don't like you), travel time, etc. Smaller hospitals do do this, sharing their burden between them, but a dedicated team has been shown to perform better.
And for specialized high risk disinfection teams, you've now suggested both that rooms need to be cleaned simultaneously, and that having a team across town is A-OK. Pick one, you really can't have both.
The lousy and getting-lousier quality of American healthcare just generally indicates that hospitals don't put profits from economies of scale or whatever else back to real improvements in safety - though they apparent put a lot of money into meals to entice returning patients (fancy meals - visible, real safety - invisible).
This really isn't true at all. Because hospitals aren't reimbursed for hospital-acquired infections, it costs them real money, and there is intense interest in improving patient safety. MRSA rates have been dropping, antibiotic stewardship programs are better, hand-washing rates are much improved, etc.
Fancy meals might be visible, but a bad case of C. difficile will cost a hospital many, many thousands of dollars. They're interested in preventing those types of infections.
I know because I work with them doing exactly that.
What's far more important is the quality of the room disinfection, which again, is a property of the room, not the number of them.
As for dedicated teams, I don't see why such things couldn't exist on a city-wide basis if they were useful.
Because now all you've done is taken the same workload, and said "Now you need to deal with 5 different smaller hospitals, five administration schemes (two of which don't like you), travel time, etc. Smaller hospitals do do this, sharing their burden between them, but a dedicated team has been shown to perform better.
And for specialized high risk disinfection teams, you've now suggested both that rooms need to be cleaned simultaneously, and that having a team across town is A-OK. Pick one, you really can't have both.
The lousy and getting-lousier quality of American healthcare just generally indicates that hospitals don't put profits from economies of scale or whatever else back to real improvements in safety - though they apparent put a lot of money into meals to entice returning patients (fancy meals - visible, real safety - invisible).
This really isn't true at all. Because hospitals aren't reimbursed for hospital-acquired infections, it costs them real money, and there is intense interest in improving patient safety. MRSA rates have been dropping, antibiotic stewardship programs are better, hand-washing rates are much improved, etc.
Fancy meals might be visible, but a bad case of C. difficile will cost a hospital many, many thousands of dollars. They're interested in preventing those types of infections.
I know because I work with them doing exactly that.
I'm honestly surprised we don't take a quarantine approach in hospitals. i.e The first sign of an infection gets you shipped out to a specialized hospital building (air gap) designed specifically to be able to keep patients in "solitary confinement" and able to be completely disinfected afterwards.
Most infectious diseases are not so dangerous that this is necessary. The ones that are, they do something like that as the other poster mentioned.
The fact of the matter though, is that a hospital for those with whatever condition is a somewhat ideal breeding ground for germs, not all of which will be deadly of course. That's not something is likely to be completely eliminated but it's something we can mitigate in a variety of ways.
The fact of the matter though, is that a hospital for those with whatever condition is a somewhat ideal breeding ground for germs, not all of which will be deadly of course. That's not something is likely to be completely eliminated but it's something we can mitigate in a variety of ways.
...this is what many infectious disease and isolation wards effectively do.
Hospital rooms with built-in autoclaves would give horror movies a lot more material to work with...
There's also some research into surfaces that combat the formation of biofilms.
>I suspect bacteria can, and will, evolve around almost any mitigating technique we develop.
That's a baseless suspicion. Bacteria are ultimately bound by physical laws, and while they've proven resilient, there's no reason to suggest we will be unable to develop the means to annihilate them at will. Humans are creative - bacteria just evolve fast.
I agree about the importance of the biofilm claim, but what they don't explain is how they actually achieve this. Their method of disabling that particular protein doesn't directly address the problem of the biofilms having a less-permeable extracellular matrix.
That's a baseless suspicion. Bacteria are ultimately bound by physical laws, and while they've proven resilient, there's no reason to suggest we will be unable to develop the means to annihilate them at will. Humans are creative - bacteria just evolve fast.
I agree about the importance of the biofilm claim, but what they don't explain is how they actually achieve this. Their method of disabling that particular protein doesn't directly address the problem of the biofilms having a less-permeable extracellular matrix.
The problem of killing bacteria, as I see it, will increasingly become something akin to the demarcation problem of philosophy. Why would it not be? It is natural that the optimal situation for pathogenic bacteria to be in is one in which they are indistinguishable from necessary cells. It may take an extraordinarily long time, but until we are able to completely eradicate a pathogenic bacteria from the earth, we will remain in that arms race.
Humans are creative at killing bacteria, though it's already not difficult to "annihilate them at will". It's much harder to annihilate only the ones we don't like, only the ones that harm us, and only the ones that pose the greatest risk.
Humans are creative at killing bacteria, though it's already not difficult to "annihilate them at will". It's much harder to annihilate only the ones we don't like, only the ones that harm us, and only the ones that pose the greatest risk.
I feel a more likely future scenario is one in which we create cell-sized robotics that we can use for very narrowly targeted operations in the human body, like treating bacteria. As the bacteria mutates, so does the targeting mechanism in the software that programs the tiny robots.
But as I said, they are ultimately bound by the laws of nature. Evolution can only happen so quickly; they can only evolve their genome so much in a given period of time.
What you're suggesting is they'll evolve to look like human cells. But that doesn't make sense. They would need to evolve that way in a single generation. Something that's "almost like" a human cell would just be wiped out.
Just consider how long it took for the last common ancestor (of humans and bacteria) to evolve into a single celled organism.
What you're suggesting is they'll evolve to look like human cells. But that doesn't make sense. They would need to evolve that way in a single generation. Something that's "almost like" a human cell would just be wiped out.
Just consider how long it took for the last common ancestor (of humans and bacteria) to evolve into a single celled organism.
I agree that we humans don't have to expect bacteria to always evolve methods to resist our medical interventions.
However, I think the most effective thing, maybe the only, we can do is actually look at the process of bacterial evolution.
That is, unless antibiotics are wildly over-used and human pathogens are concentrated in one place facing constant medical intervention, human medical intervention is going to be a very small, unimportant part of bacterial evolution.
Unfortunately, antibiotics are widely over used and pathogens are concentrated in poor administered hospitals.
If we stop these practices and we could stop these practices, then antibiotic-resistant bacteria would have little evolutionary incentive to exist.
That is, unless antibiotics are wildly over-used and human pathogens are concentrated in one place facing constant medical intervention, human medical intervention is going to be a very small, unimportant part of bacterial evolution.
Unfortunately, antibiotics are widely over used and pathogens are concentrated in poor administered hospitals.
If we stop these practices and we could stop these practices, then antibiotic-resistant bacteria would have little evolutionary incentive to exist.
> Unfortunately, antibiotics are widely over used and pathogens are concentrated in poor administered hospitals.
Some countries have people who sell incomplete courses of anti biotics, without a prescription.[1] Someone can buy a few days worth of pills - enough to get them over the illness, but also enough to promote anti biotic resistance.
For example, people in India die from pnumonia (largest killer of children in India) and these people need to use antibiotics. They often can't afford a complete course. And then other people misuse antibiotics for simple diarrhoea, which isn't helped with antibiotics.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193708/
> The bacterial disease burden in India is among the highest in the world1; consequently, antibiotics will play a critical role in limiting morbidity and mortality in the country. As a marker of disease burden, pneumonia causes an estimated 410,000 deaths in India each year2, and it is the number-one killer of children3. Many of these deaths occur because patients do not have access to life-saving antibiotics when and where these are needed. At the other extreme, antibiotics are used in situations where these cannot be expected to improve the patient's condition, particularly as treatment for the common cold and uncomplicated cases of diarrhoea (which are appropriately treated with oral rehydration therapy).
[1] http://www.thehindu.com/sci-tech/health/policy-and-issues/an...
> The rise is substantial in the retail sector where antibiotics are mostly sold without a prescription,
Some countries have people who sell incomplete courses of anti biotics, without a prescription.[1] Someone can buy a few days worth of pills - enough to get them over the illness, but also enough to promote anti biotic resistance.
For example, people in India die from pnumonia (largest killer of children in India) and these people need to use antibiotics. They often can't afford a complete course. And then other people misuse antibiotics for simple diarrhoea, which isn't helped with antibiotics.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3193708/
> The bacterial disease burden in India is among the highest in the world1; consequently, antibiotics will play a critical role in limiting morbidity and mortality in the country. As a marker of disease burden, pneumonia causes an estimated 410,000 deaths in India each year2, and it is the number-one killer of children3. Many of these deaths occur because patients do not have access to life-saving antibiotics when and where these are needed. At the other extreme, antibiotics are used in situations where these cannot be expected to improve the patient's condition, particularly as treatment for the common cold and uncomplicated cases of diarrhoea (which are appropriately treated with oral rehydration therapy).
[1] http://www.thehindu.com/sci-tech/health/policy-and-issues/an...
> The rise is substantial in the retail sector where antibiotics are mostly sold without a prescription,
Humans are creative - bacteria just evolve fast
Yeah, but once we get good enough to annihilate them at will we will also have a similar power to improve them through tinkering.
Just like computer viruses continue to be developed by people, biological agents will be developed as well.
Some human tinkering will be for the heck of it. Some will be government level projects that get out of control. Eventually, organized crime will be in on the action.
Imagine Cryptolocker (http://en.wikipedia.org/wiki/CryptoLocker) but with a biological agent.
Yeah, but once we get good enough to annihilate them at will we will also have a similar power to improve them through tinkering.
Just like computer viruses continue to be developed by people, biological agents will be developed as well.
Some human tinkering will be for the heck of it. Some will be government level projects that get out of control. Eventually, organized crime will be in on the action.
Imagine Cryptolocker (http://en.wikipedia.org/wiki/CryptoLocker) but with a biological agent.
It's certainly possible that one day we'll have desktop genome-printers. Any technology can (and often is) abused, and that would be no exception. Hopefully, there will be a Kaspserky for this era. A "Gene Kaspersky", if you will.
killing bacteria alone isnt a problem. Killing bacteria while keeping a human alive starts to complicate the problem. Killing certain bacteria while keeping a human and the rest of said humans helpful bacteria alive but not resistant to anti-bodies, is a whole different ballgame...
>killing bacteria alone isnt a problem. Killing bacteria while keeping a human alive starts to complicate the problem.
Thank you Captain Obvious.
Thank you Captain Obvious.
You'd think this was "Captain Obvious", but this is genuinely a challenge for some bacterial infections. Its even worse for fungal infections, as fungi are eukaryotic and thus share a alarming number of potential drug targets with human cells.
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> it only works the bacteria known as gram-positives, which includes problematic bugs like Staphylococcus
I have had one of those for almost a decade now.
> He hasn’t tested it in humans yet
How long is the road ahead before it becomes available to regular patients? Should I get my hopes up?
I have had one of those for almost a decade now.
> He hasn’t tested it in humans yet
How long is the road ahead before it becomes available to regular patients? Should I get my hopes up?
It's going to be a long time before it is readily available for human use. Expect three, maybe four stages of clinical trials. There is also the risk that it doesn't even work in humans or has major side effects that outweigh the benefit.
This is sensationalism news, or as it is most often called, news.
This is sensationalism news, or as it is most often called, news.
I would call it a sensationalist title, but the article itself is far from sensational.
I actually found the writing to be pleasantly balanced and scientifically detailed, without jumping to unreasonable conclusions.
I actually found the writing to be pleasantly balanced and scientifically detailed, without jumping to unreasonable conclusions.
Consider writing to the researchers volunteering for a clinical trial.
It does, of course, involve a certain risk. You should do a lot of thinking before taking such a leap.
It does, of course, involve a certain risk. You should do a lot of thinking before taking such a leap.
>I have had one of those for almost a decade now.
Sinuses?
Sinuses?
No, just an ear infection. More annoying than anything. Although it does supposedly carry some risk of hearing loss should it come back hard.
Wait, how did you figure this out? I worry about having some sort of chronic infection..
I went to the doctor when I caught it originally, and then a few years later again when it came back. Although the first doc warned me that it might come back and is hard to get rid of completely, so it wasn't entirely unexpected.
You are most likely eating something you are intolerant to.
You need to do an elimination diet, SCD diet, and eliminate all grains temporarily.
Curing this with antibiotics would only be a temporary solution, and antibiotics in general are not a good strategy for dealing with long term infections.
You need to do an elimination diet, SCD diet, and eliminate all grains temporarily.
Curing this with antibiotics would only be a temporary solution, and antibiotics in general are not a good strategy for dealing with long term infections.
Thanks for the feedback. As relates to sinuses, is the theory that the infection is a product of food-induced inflammatory conditions that don't allow for proper drainage?
Because, some of my experience would suggest that it may be exacerbated by inflammation somewhat, but the primary cause is a persistent reservoir of bacteria. This could be a biofilm or otherwise dormant bacteria as described in the article. Actually, the latter is much more plausible as and, in all the time I have been dealing with this, no physician has ever mentioned that bacteria even have such a dormant state.
Because, some of my experience would suggest that it may be exacerbated by inflammation somewhat, but the primary cause is a persistent reservoir of bacteria. This could be a biofilm or otherwise dormant bacteria as described in the article. Actually, the latter is much more plausible as and, in all the time I have been dealing with this, no physician has ever mentioned that bacteria even have such a dormant state.
Sorry to hear that. Been dealing with similar of the sinuses myself for about the same period of time.
Definitely no fun, but this does sound promising. Good luck to us all.
Definitely no fun, but this does sound promising. Good luck to us all.
Have you tried nose rinses? My ENT prescribed those and that helped.
Have I? LOL.
Seriously, I've tried pretty much everything (medical and alternative). And, actually, the saline rinses helped some, but didn't prevent the infection from re-emerging or clear it once it did.
Then, someone mentioned adding fresh garlic (steeped, like tea) to the saline rinse. Sounded nuts so I didn't bother for a year. Finally got fed up enough to try it and amazed to find that it works better than any medical treatment thus far. I'd recommend it, but it's a pain to prepare, smells, and is not a cure (i.e. you have to continue to do it regularly to keep the infection at bay).
That's why something like the subject post is hopeful.
Seriously, I've tried pretty much everything (medical and alternative). And, actually, the saline rinses helped some, but didn't prevent the infection from re-emerging or clear it once it did.
Then, someone mentioned adding fresh garlic (steeped, like tea) to the saline rinse. Sounded nuts so I didn't bother for a year. Finally got fed up enough to try it and amazed to find that it works better than any medical treatment thus far. I'd recommend it, but it's a pain to prepare, smells, and is not a cure (i.e. you have to continue to do it regularly to keep the infection at bay).
That's why something like the subject post is hopeful.
If this is a novel antibiotic with any therapeutic potential, please let's outlaw feeding it to cattle by the ton.
Pretty much exactly what I was going to post. Prophylactic use of antibiotics in hogs/whatever is stupidity in a class of its' own, selectively breeding organisms on an industrial scale for resistance to the drugs we might want to use to keep us alive.
This is an awful headline change. National Geographic's title (Killing Sleeper Cells and Superbugs with Assassin Janitors) wasn't very descriptive, but at least it didn't leave room for a headline browser to take away the false conclusion that the CDC declared public health crisis of antibiotic resistance is near resolution.
According to the article, this new antibiotic has only been tested on mice and rats. These sort of preliminary results go bust all the time, and so I think that in this case, it's irresponsible to fail to indicate that these are preliminary studies and that the effect hasn't been demonstrated in humans. This could have been achieved by leaving the title the same, or by changing it to "New antibiotic kills off persistent infections in rats".
According to the article, this new antibiotic has only been tested on mice and rats. These sort of preliminary results go bust all the time, and so I think that in this case, it's irresponsible to fail to indicate that these are preliminary studies and that the effect hasn't been demonstrated in humans. This could have been achieved by leaving the title the same, or by changing it to "New antibiotic kills off persistent infections in rats".
Reading about new treatments gives me a kind of anxiety: drug trials are so slow and the funding models are so removed from the actual human life-saving potential, that I just am filled with fear that this stuff will get mired in bureaucracy or otherwise defunded rather than getting FDA approved. I dread the idea that someone I know to get sick and die because we're so ploddingly slow at doing these trials.
For example: "DRACO" antivirals from MIT, were developed in 2011, and according to mouse model tests and tests on cultured human cells, is safe and effective against influenza and rhinovirus and everything else they threw at it (see http://mackinstitute.wharton.upenn.edu/wp-content/uploads/20... for details), and yet it could be a decade before we even try to answer questions like "wait, does this cure HIV? It sounds like it might actually cure HIV"
For example: "DRACO" antivirals from MIT, were developed in 2011, and according to mouse model tests and tests on cultured human cells, is safe and effective against influenza and rhinovirus and everything else they threw at it (see http://mackinstitute.wharton.upenn.edu/wp-content/uploads/20... for details), and yet it could be a decade before we even try to answer questions like "wait, does this cure HIV? It sounds like it might actually cure HIV"
The funding models actually aren't removed from the actual human life-saving potential. The NIH has been pushing translational research pretty heavily, and if anything there's been a fair amount of pressure on the basic science types to tie their research to something, anything that will manifest in Saving Lives.
Beyond that, it absolutely should take drugs many years to come to market. Research is hard. Research on human beings is very hard. You can't just take shots in the dark and hope something sticks - you have to understand how, and how well, something works. Even for the established antivirals we do have for HIV, we're still trying to figure out who to give them to and when.
Beyond that, it absolutely should take drugs many years to come to market. Research is hard. Research on human beings is very hard. You can't just take shots in the dark and hope something sticks - you have to understand how, and how well, something works. Even for the established antivirals we do have for HIV, we're still trying to figure out who to give them to and when.
The bacteria evolving to go dormant reminds me scale insects that damaged citrus fruits. The farmers put a giant tent over every tree and gassed them. This worked at first, but after a few years the scale insects got resistant. Whenever startled, they would sit perfectly still and hold their breath for half an hour.
It's nice to know that despite all the alarmist articles about the end of antibiotics, good progress is being made. If this works, it could completely replace traditional antibiotics. In that case, I could see dozens of new drugs in this class developed by the antibiotic companies. This would be similar to the race to develop new antidepressants, HIV drugs, and erectile dysfunction drugs. Any drug you have to take over and over again is a huge draw for the pharmaceuticals.
This won't completely replace traditional antibiotics. As the article states this acts on Gram positive persister cells (a very specific group). The coming storm is from Gram negative bacteria such as Klebsiella, Actinetobacter and Pseudomonas.
There is actually very little activity occurring in the field of antibiotic drug discovery and you identified the issue; no money in drugs that someone takes for 14 days and stops. Pharmaceutical companies are driven by stockholders and therefore they want them developing drugs that someone takes for the rest of their life (anti-depressants). Much of the research for abx discovery comes from academia who struggle with budgets that are pennies compared to what Pfizer, GSK, Wyeth, Astra can afford.
There is actually very little activity occurring in the field of antibiotic drug discovery and you identified the issue; no money in drugs that someone takes for 14 days and stops. Pharmaceutical companies are driven by stockholders and therefore they want them developing drugs that someone takes for the rest of their life (anti-depressants). Much of the research for abx discovery comes from academia who struggle with budgets that are pennies compared to what Pfizer, GSK, Wyeth, Astra can afford.
You're right that it's about profits when pharma is involved, but you are wrong about the reason (otherwise vaccines would not exist). I can tell you from firsthand experience that the length of time someone is on a drug makes almost no difference in where research priorities are.
The primary issue with antibiotics is that since the late 1990's, if you succeed, and you develop the best antibiotic the world has ever seen, the FDA will require it to be a "drug of last resort". It will therefore sit on the shelf and be guaranteed to not be prescribed very much during the life of its patent. Once enough time goes by, and other drugs come out if (and that's a big if) it is no longer a drug of last resort, it is likely off patent and therefore can be made in generic form for pennies by generic manufacturers. Regardless of what you think about patents, these incentives are completely misaligned with companies going all-in and taking a risk on new antibiotics.
The primary issue with antibiotics is that since the late 1990's, if you succeed, and you develop the best antibiotic the world has ever seen, the FDA will require it to be a "drug of last resort". It will therefore sit on the shelf and be guaranteed to not be prescribed very much during the life of its patent. Once enough time goes by, and other drugs come out if (and that's a big if) it is no longer a drug of last resort, it is likely off patent and therefore can be made in generic form for pennies by generic manufacturers. Regardless of what you think about patents, these incentives are completely misaligned with companies going all-in and taking a risk on new antibiotics.
Vaccines are a bit of a different class as some are exempt from adverse reaction lawsuits and therefore risk is reduced for the companies manufacturing the vaccine.
I think your assessment that my argument is "wrong" is inappropriate. You'll see that my argument is supported by the WHO (Bulletin of the World Health Organization 2011;89:88–89).
>Another reason is commercial. Antibiotics, in particular, have a poor return on investment because they are taken for a short period of time and cure their target disease. In contrast, drugs that treat chronic illness, such as high blood pressure, are taken daily for the rest of a patient’s life. “Companies have figured out that they make a lot more money selling the latter drugs than they do selling antibiotics,” Spellberg says, highlighting the lack of incentive for companies to develop antibiotics.
I think your assessment that my argument is "wrong" is inappropriate. You'll see that my argument is supported by the WHO (Bulletin of the World Health Organization 2011;89:88–89).
>Another reason is commercial. Antibiotics, in particular, have a poor return on investment because they are taken for a short period of time and cure their target disease. In contrast, drugs that treat chronic illness, such as high blood pressure, are taken daily for the rest of a patient’s life. “Companies have figured out that they make a lot more money selling the latter drugs than they do selling antibiotics,” Spellberg says, highlighting the lack of incentive for companies to develop antibiotics.
And yet in a recent survey of drug development costs, "Difficid", by Optimer Pharmaceuticals, was one of the most inexpensive to develop.
I also really don't buy the "return on investment" argument, as curing a bacterial disease rarely provides immunity.
It's also not my experience as a researcher in the area - several drug companies are actively funding research.
I also really don't buy the "return on investment" argument, as curing a bacterial disease rarely provides immunity.
It's also not my experience as a researcher in the area - several drug companies are actively funding research.
Fidaxo also may not be that great or cost effective[1]. Optimer, I believe has been bought by Cubist and delisted from Nasdaq. 1. Clin Infect Dis. 2013 Aug;57(4):555-61
I do know their most promising findings don't get reflected in clinical trials well. But "The Drug Companies aren't there" isn't addressed by a small drug company specializing in ID getting bought about by another drug company that has tons of ID products for half a billion dollars.
As a citizen of earth and a member of humanity it hurts to hear that people who's very business is saving lives are largely driven by profits for their company and not the goal of the company: saving lives. While I know this naive I wish it weren't.
Do you know if NIH uses any of their funding in a DARPA like manner?
They do this to a certain extent, but the problem here is that the "R" part of "R&D" is not really at issue. While there's a lot of focus in the popular press on "finding" new antibiotics, that part can be addressed by basic research grants. I don't believe we're wanting for proof of concept kinds of things. Unlike with engineering, where once you've got a proof of concept, you can refine and iterate to make it production quality, biology is completely arbitrary.
The issue comes with the "D" part of R&D. That is the expensive part with drugs because you start having to do very tightly controlled animal model studies progressing further into clinical trials with humans. The popular notion that you "discover" a drug is not how things work in reality. Often you discover a whole raft of closely related chemical entities that appear to do what you think they do. You tweak based on further studies in order to improve efficacy and safety. But the system is sort of nondeterministic in the sense that even altering the structure slightly often has knock-on effects you can't predict. Assuming you get something decent, that's what gets made into the an actual medicine. There's a whole branch of applied chemistry that specializes in this called medicinal chemistry. In many cases, you'll read about some promising new antibiotic that has been discovered in an academic lab, but once the chemists take a look at it, you realize there's no way to make a drug out of it. The reasons can be any or all of: the therapeutic dose would be too high, it blows out the liver, it can't be made into pill, the compound is unstable and can't have a good shelf life, it can't be taken orally, etc... Working out all those kinds of problems has always been the realm of pharmas and biotech startups. Academics aren't interested in that stuff because it's not basic research, it's highly applied and is mostly trial and error based on decades of doing this kind of work.
At a macro-level, this is fundamentally what ails the entire pharma sector right now. The development part of making drugs is so expensive and such a complete and utter crap-shoot, that few new drugs of any sort are actually being produced. The last decade has been one of prolonged decline in the industry in terms of truly new drugs and there is no obvious mechanism available to us to make it less so.
The issue comes with the "D" part of R&D. That is the expensive part with drugs because you start having to do very tightly controlled animal model studies progressing further into clinical trials with humans. The popular notion that you "discover" a drug is not how things work in reality. Often you discover a whole raft of closely related chemical entities that appear to do what you think they do. You tweak based on further studies in order to improve efficacy and safety. But the system is sort of nondeterministic in the sense that even altering the structure slightly often has knock-on effects you can't predict. Assuming you get something decent, that's what gets made into the an actual medicine. There's a whole branch of applied chemistry that specializes in this called medicinal chemistry. In many cases, you'll read about some promising new antibiotic that has been discovered in an academic lab, but once the chemists take a look at it, you realize there's no way to make a drug out of it. The reasons can be any or all of: the therapeutic dose would be too high, it blows out the liver, it can't be made into pill, the compound is unstable and can't have a good shelf life, it can't be taken orally, etc... Working out all those kinds of problems has always been the realm of pharmas and biotech startups. Academics aren't interested in that stuff because it's not basic research, it's highly applied and is mostly trial and error based on decades of doing this kind of work.
At a macro-level, this is fundamentally what ails the entire pharma sector right now. The development part of making drugs is so expensive and such a complete and utter crap-shoot, that few new drugs of any sort are actually being produced. The last decade has been one of prolonged decline in the industry in terms of truly new drugs and there is no obvious mechanism available to us to make it less so.
In fairness, the NIH has started pushing "translational research" really hard in recent years.
"no money in drugs that someone takes for 14 days and stops. Pharmaceutical companies are driven by stockholders"
You wonder of course why, if that is the case (and I do agree), that the government doesn't get involved with more funding or subsidies for these types of less profitable drugs. The same way they spend countless dollars on other things for the public good (and company profit obviously).
You wonder of course why, if that is the case (and I do agree), that the government doesn't get involved with more funding or subsidies for these types of less profitable drugs. The same way they spend countless dollars on other things for the public good (and company profit obviously).
They have gotten involved in lightening the regulatory burden for certain drugs that are orphaned or for rare diseases, which is essentially a subsidy.
Also, the number of drug company booths at a recent infectious disease conference I went to suggests this whole "No interest in drugs that cure in three weeks" thing is...well...not actually true. These are incredibly common infections, there's plenty of market for them. Hell, the compound was initially discovered by Bayer.
Also, the number of drug company booths at a recent infectious disease conference I went to suggests this whole "No interest in drugs that cure in three weeks" thing is...well...not actually true. These are incredibly common infections, there's plenty of market for them. Hell, the compound was initially discovered by Bayer.
I wondered about this and looked it up (leading to my other comment in this thread). NIH has a $30 billion medical research budget. DARPA is a couple of billion. Of course the $30 billion is not all directed at less profitable drugs.
Apparently there are a bunch of hard problems there.
Apparently there are a bunch of hard problems there.
The government is involved, but through academia. For example in Canada we have the CIHR (Canadian Institutes of Health Research) which would fund develop of drug develop (among many other health research).
Sounds like something the Gates Foundation should get on.
The scary thing is what would happen if these bacteria fell into the hands of terrorist extremists. They could potentially create bio-weapons of mass destruction. Or imagine if some suicide cult decided that the time has come for the doomsday of reckoning. Al-Qaeda anthrax letters are nothing compared to this. It could also be used to threaten mutually assured destruction in asymmetric warfare. Iran could probably develop it more easily and stealthily than their (not very) secret nuke program. Developing countermeasure to this is a matter of national security. Insha'Allah people will come to their senses and please think of the children: We must secure the existence of our people and a future for white children before it is too late.
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This is really fantastic news but I too am skeptical of the drug companies being interested in a cure as opposed to a repeatable treatment.
As a side note the article seems very well written for non-medical folks like myself.
As a side note the article seems very well written for non-medical folks like myself.
This line of reasoning doesn't really apply to antibiotics - because you're likely to get another infection in your lifetime, and many people have infections at any given time, they're perfectly fine eradicating this one.
Believe me, in the infectious disease space, drug companies tend to look for cures and prevention. For example, Merck and GSK spent staggering amounts of money on the HPV vaccine.
Believe me, in the infectious disease space, drug companies tend to look for cures and prevention. For example, Merck and GSK spent staggering amounts of money on the HPV vaccine.
That's very good news actually. If first stage trials are successful might be marketed sooner than expected. However, I didn't read the paper, so I can't comment on the mechanism of action which the mos interesting part of an drug. Bacteria might become resistant if this procedure becomes overused (as usual) and it would be a shame.
Very interesting research but it doesn't mention any negatives of ADEP4. What kind of effects could it have on the human body?
Many antibiotics are fairly nasty drugs - they're associated with kidney failure and other negative outcomes, especially for long term treatment. But it's hard to know for sure until things progress to the point where we are doing toxicity studies.
Which you don't bother with until you know the thing can work in the first place.
Which you don't bother with until you know the thing can work in the first place.
I wonder if this approach will eventually be useful in eliminating Chronic Lyme Disease.
Doubtful, as there's little to no scientific evidence that Chronic Lyme Disease is actually a bacterial infection.
That's actually a bit of a dated response:
See recent study on Rhesus monkeys: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourna...
The "no bacteria" perspective is usually based off of IDSA guidelines. Unfortunately, they've been successfully litigated against for providing incorrect information that appear to be linked to financial interests:
"My office uncovered undisclosed financial interests held by several of the most powerful IDSA panelists. The IDSA's guideline panel improperly ignored or minimized consideration of alternative medical opinion and evidence regarding chronic Lyme disease, potentially raising serious questions about whether the recommendations reflected all relevant science."
http://www.ct.gov/ag/cwp/view.asp?a=2795&q=414284
Good summary of Lyme: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636972/
Needless to say, we've got a lot of people we're telling that they are not sick when symptomatically they appear to be.
See recent study on Rhesus monkeys: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjourna...
The "no bacteria" perspective is usually based off of IDSA guidelines. Unfortunately, they've been successfully litigated against for providing incorrect information that appear to be linked to financial interests:
"My office uncovered undisclosed financial interests held by several of the most powerful IDSA panelists. The IDSA's guideline panel improperly ignored or minimized consideration of alternative medical opinion and evidence regarding chronic Lyme disease, potentially raising serious questions about whether the recommendations reflected all relevant science."
http://www.ct.gov/ag/cwp/view.asp?a=2795&q=414284
Good summary of Lyme: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636972/
Needless to say, we've got a lot of people we're telling that they are not sick when symptomatically they appear to be.
"Pursuant to their agreement with Blumenthal the IDSA guidelines were reviewed by an independent panel subject to strict conflict-of-interest guidelines and vetted by a medical ethicist. The panel supported the original IDSA guidelines, finding that "chronic Lyme disease" and "post Lyme syndrome" lack clear definitions and convincing biological evidence. Further, the report emphasized that several prospective clinical trials of prolonged antibiotic therapy for persistently symptomatic patients uniformly showed evidence of harm without convincing evidence of benefit.[22] Nonetheless, some groups have continued to criticize the IDSA guidelines after the 2012 review.[23] [24]"
https://en.wikipedia.org/wiki/Infectious_Diseases_Society_of...
Also, see your sibling post by me with info from the CDC. It doesn't seem like they're dismissing the symptoms, they're just saying that antibiotics don't help.
https://en.wikipedia.org/wiki/Infectious_Diseases_Society_of...
Also, see your sibling post by me with info from the CDC. It doesn't seem like they're dismissing the symptoms, they're just saying that antibiotics don't help.
I've watched my mother suffer from this for 20+ years. She initially had a doctor that treated her for 3 years with very strong antibiotics. She made remarkable progress. The doctor left practicing for personal reasons and subsequently she couldn't find good medical help. Her condition deteriorated over the years.
While the CDC doesn't seem to dismiss symptoms, I've watched dozens of doctors dismiss her. I've received calls from dozens of people who all have the same set of symptoms. I've also seen people get better only after years of antibiotic treatment, and slowly at that. My friends in medical school have indicated that they receive about two hours of Lyme-related training during their education.
The issue that you have is three-fold:
1. Ticks often carry multiple infections (Borrelia Burgdoferi, Bartonella, Mycoplasma, and Babesiosis). Each of these infections can leave the immune system in a dysfunctional state. Most studies only focus on treatment of BB, leaving the other infections untouched.
2. Given that, for the toughest cases, years of antibiotics may be needed, it is extremely difficult to keep studies "controlled". i.e. a week long study may not have much variability, but over a two-year study, a lot happens. The noise increases relative to the signal.
3. BB has very high genetic variability. This leads to the potential for larger numbers of strains, with over 200 thought to be in existence.
I'm not contesting that this isn't well-understood. In fact, I fully agree with that. But statements like there is little to no evidence that Chronic Lyme exists are inappropriate. This is an area that has historically been underfunded, and it has a pretty rich history of controversy. We can fight over nomenclature all day long, but that doesn't change the fact that a lot of people are suffering, and the broader medical community is woefully uninformed.
While the CDC doesn't seem to dismiss symptoms, I've watched dozens of doctors dismiss her. I've received calls from dozens of people who all have the same set of symptoms. I've also seen people get better only after years of antibiotic treatment, and slowly at that. My friends in medical school have indicated that they receive about two hours of Lyme-related training during their education.
The issue that you have is three-fold:
1. Ticks often carry multiple infections (Borrelia Burgdoferi, Bartonella, Mycoplasma, and Babesiosis). Each of these infections can leave the immune system in a dysfunctional state. Most studies only focus on treatment of BB, leaving the other infections untouched.
2. Given that, for the toughest cases, years of antibiotics may be needed, it is extremely difficult to keep studies "controlled". i.e. a week long study may not have much variability, but over a two-year study, a lot happens. The noise increases relative to the signal.
3. BB has very high genetic variability. This leads to the potential for larger numbers of strains, with over 200 thought to be in existence.
I'm not contesting that this isn't well-understood. In fact, I fully agree with that. But statements like there is little to no evidence that Chronic Lyme exists are inappropriate. This is an area that has historically been underfunded, and it has a pretty rich history of controversy. We can fight over nomenclature all day long, but that doesn't change the fact that a lot of people are suffering, and the broader medical community is woefully uninformed.
Your "Good summary" is in a journal that's pretty far from what I'd call reputable. The PLOS One article on Rhesus monkeys isn't terribly definitive either - it's a big step between persisting in a host and capable of producing disease without manifesting any laboratory detectable presence.
To jump from "This might be a cause" to "Lets treat people with long term courses of antibiotics, which have known and often severe side effects" is a pretty serious leap in logic.
And I know very few clinicians who would tell someone who believes they're suffering from "Chronic Lyme" that they're not sick. Just that they're not sick in this particular way. Non-specific, widespread inflammatory disease is something the medical community is still struggling to figure out. But antibiotics are fairly nasty drugs for "We have no way of diagnosing this, fleeting evidence for a causal link, and no population-level studies."
To jump from "This might be a cause" to "Lets treat people with long term courses of antibiotics, which have known and often severe side effects" is a pretty serious leap in logic.
And I know very few clinicians who would tell someone who believes they're suffering from "Chronic Lyme" that they're not sick. Just that they're not sick in this particular way. Non-specific, widespread inflammatory disease is something the medical community is still struggling to figure out. But antibiotics are fairly nasty drugs for "We have no way of diagnosing this, fleeting evidence for a causal link, and no population-level studies."
Would you agree that a medical journal's impact factor is more important for new research than a summary? I would think that for a summary the quantity and quality of the references is a bigger factor.
As far as the clinicians, having a lot of family experience with the disease, I've seen things far differently. This in addition to support groups, phone calls, etc. We're not going to get anywhere debating experience, just letting you know that it happens a lot.
As far as the clinicians, having a lot of family experience with the disease, I've seen things far differently. This in addition to support groups, phone calls, etc. We're not going to get anywhere debating experience, just letting you know that it happens a lot.
Honestly no - for a review article, I generally prefer journals with a better reputation. Not necessarily based on Impact Factor, but I'd much rather rely on a non-systematic review from JAMA, Lancet ID, JID, JAMA or PLOS Medicine. Or any one of a number of specialty or society level journals.
I'd rather not rely on an article from an OA factory that's spammy enough for people to wonder if its a scam journal. For a systematic review or meta-analysis I might let it slide, but this was an opinion-y "Review of the Evidence". The somewhat wide ranging stuff the author writes on makes me a little skittish as well.
I'm sorry to hear of your family's experience. I occasionally have my own issues with clinicians.
I'd rather not rely on an article from an OA factory that's spammy enough for people to wonder if its a scam journal. For a systematic review or meta-analysis I might let it slide, but this was an opinion-y "Review of the Evidence". The somewhat wide ranging stuff the author writes on makes me a little skittish as well.
I'm sorry to hear of your family's experience. I occasionally have my own issues with clinicians.
Hm, that's interesting.
"Approximately 10 to 20% of patients treated for Lyme disease with a recommended 2–4 week course of antibiotics will have lingering symptoms of fatigue, pain, or joint and muscle aches. In some cases, these can last for more than 6 months. Although often called 'chronic Lyme disease,' this condition is properly known as 'Post-treatment Lyme Disease Syndrome' (PTLDS).
The exact cause of PTLDS is not yet known. Most medical experts believe that the lingering symptoms are the result of residual damage to tissues and the immune system that occurred during the infection. Similar complications and 'auto–immune' responses are known to occur following other infections . . .
Regardless of the cause of PTLDS, studies have not shown that patients who received prolonged courses of antibiotics do better in the long run than patients treated with placebo."
http://www.cdc.gov/lyme/postLDS/index.html
"Approximately 10 to 20% of patients treated for Lyme disease with a recommended 2–4 week course of antibiotics will have lingering symptoms of fatigue, pain, or joint and muscle aches. In some cases, these can last for more than 6 months. Although often called 'chronic Lyme disease,' this condition is properly known as 'Post-treatment Lyme Disease Syndrome' (PTLDS).
The exact cause of PTLDS is not yet known. Most medical experts believe that the lingering symptoms are the result of residual damage to tissues and the immune system that occurred during the infection. Similar complications and 'auto–immune' responses are known to occur following other infections . . .
Regardless of the cause of PTLDS, studies have not shown that patients who received prolonged courses of antibiotics do better in the long run than patients treated with placebo."
http://www.cdc.gov/lyme/postLDS/index.html
That's fair, but keep in mind that the CDC this year revised their estimates of people with Lyme 10x. This suggests that they've had a strained understanding of the problem.
http://www.pbs.org/newshour/bb/health/july-dec13/lyme_08-20....
http://www.pbs.org/newshour/bb/health/july-dec13/lyme_08-20....
But does it kill the host as well?
can it be tested on Google+?
> New antibiotic kills off persistent infections
Now available in hand-soap.
Now available in hand-soap.
oh god damn it >:(
What's that? Inject the hand-soap directly into my veins?
This class of antibiotics, ADEP, was discovered as a naturally produced substance isolated from the bacteria Streptomyces hawaiiensis in 1985 (Streptomyces has been a fertile source of naturally occurring antibiotics). After some promising results, there was work on synthetically synthesizing it and producing "optimized" synthetic variants. ADEP4 is one of those, and was reported in a paper published in 2005. There's a short 1-page summary of that work in Nature Reviews Drug Discovery 4: 957. See page 19 of this PDF, article "Peptide power": http://journals2005.pasteur.ac.ir/NR/4%2812%29.pdf
There's a lot of work trying to understand its mechanism, e.g. here's one open-access paper that also has some background: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2955292/
Here's the paper discussed in the linked article, unfortunately paywalled, but with an abstract available that's actually a good summary: http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...