My Husband Became a Poster Child of the Post-Antibiotic Era(thedailybeast.com)
thedailybeast.com
My Husband Became a Poster Child of the Post-Antibiotic Era
https://www.thedailybeast.com/how-my-husband-became-a-poster-child-of-the-post-antibiotic-superbug-era
14 comments
> This article yet again reports on the lack of awareness about bacteriophages in the medical community.
A shortlist of answers:
- Bacteriophages are evolutionarily close to viruses. Their proteins will resemble viral proteins, so the body will most likely initiate an immune response against it.
- Bacteriophages are really quite specific in what they'll infect. This makes them much less useful as an antibacterial. You'd spend a lot of time and money on making one that would infect your mrsa strain, and mrsa would probably just start the arms race, leaving you back at the start.
- Bacteriophages are (evolutionarily close to) viruses, and thus also have the immense mutation rate of those. Even if you were to make one that had all the properties you wanted, it'd probably get rid of most of them because they are evolutionarily disadvantages.
- Probably a few other fairly good reasons which my coffee-deprived brain can't think off right at this moment.
A shortlist of answers:
- Bacteriophages are evolutionarily close to viruses. Their proteins will resemble viral proteins, so the body will most likely initiate an immune response against it.
- Bacteriophages are really quite specific in what they'll infect. This makes them much less useful as an antibacterial. You'd spend a lot of time and money on making one that would infect your mrsa strain, and mrsa would probably just start the arms race, leaving you back at the start.
- Bacteriophages are (evolutionarily close to) viruses, and thus also have the immense mutation rate of those. Even if you were to make one that had all the properties you wanted, it'd probably get rid of most of them because they are evolutionarily disadvantages.
- Probably a few other fairly good reasons which my coffee-deprived brain can't think off right at this moment.
> You'd spend a lot of time and money on making one that would infect your mrsa strain, and mrsa would probably just start the arms race, leaving you back at the start.
Actually developing resistance against bacteriophages requires such invasive changes that most bacteria that develop it lose resistance against anti-biotics. That is why an anti-biotic therapy is often used together with a phage therapy.
Actually developing resistance against bacteriophages requires such invasive changes that most bacteria that develop it lose resistance against anti-biotics. That is why an anti-biotic therapy is often used together with a phage therapy.
> Actually developing resistance against bacteriophages requires such invasive changes that most bacteria that develop it lose resistance against anti-biotics
It requires some huge changes, sure. However, MRSA exists because Staph was able to adapt to be resistant to multiple antibiotics at the same time. There is no reason to assume that it could not adapt to become resistant to the phage used as well as some of the most used antibiotics.
It requires some huge changes, sure. However, MRSA exists because Staph was able to adapt to be resistant to multiple antibiotics at the same time. There is no reason to assume that it could not adapt to become resistant to the phage used as well as some of the most used antibiotics.
You also get the evolutionary war between the virus and the bacteria. That should help out.
Those are all potentially valid reasons to not pay much attention to it as a solution for multi-resistant bacteria.
However, none of them explain why medical professionals are not even aware that bacteriophages are a thing, in contrast with laypeople like the parent poster (or myself, and presumably many more on HN since there have been a few articles on this topic over the years).
However, none of them explain why medical professionals are not even aware that bacteriophages are a thing, in contrast with laypeople like the parent poster (or myself, and presumably many more on HN since there have been a few articles on this topic over the years).
The medical profession is aware, they just aren’t scaled up for use in any meaningful sense - essentially to be able to meaningfully fight bacterial infections with phases a hospital or clinic would need to type the bacteria and screen it against potentially hundreds or more phages (even if they are already specific to the bacteria) to find the ones that are going to be most effective.
So, there are time constraints, delivery mechanisms and also logistics to overcome.
A challenge for a startup?
A challenge for a startup?
> why medical professionals are not even aware that bacteriophages are a thing
Sounds questionable to me that this is even the cause, to be honest. However, assuming this is true, the main reason I could think for why would be the case if this: medicine is an extremely specialised field. Not only do you focus solely on the human body, but not even the body as a whole, but on what can go wrong with it. The only knowledge a medical professional needs about bacteria, viruses and other pathogens is what they require for them to be diagnozed, what kind of illnesses they convey and how they can be gotten rid of. And not even this is accurate, because within the field of medicine there's even further specialisation into even smaller sub-fields.
That there are also viruses which infect bacteria is of no (direct) importance on the medical field. In fact, it'd frankly be a waste of time for them during their study to learn about phages in any detail. The basic degree alone is already very long and full to the point of bursting. It'd be similar to expecting welders to understand the minutea of all states of matter, because TIG welding uses plasma to melt metal.
Sounds questionable to me that this is even the cause, to be honest. However, assuming this is true, the main reason I could think for why would be the case if this: medicine is an extremely specialised field. Not only do you focus solely on the human body, but not even the body as a whole, but on what can go wrong with it. The only knowledge a medical professional needs about bacteria, viruses and other pathogens is what they require for them to be diagnozed, what kind of illnesses they convey and how they can be gotten rid of. And not even this is accurate, because within the field of medicine there's even further specialisation into even smaller sub-fields.
That there are also viruses which infect bacteria is of no (direct) importance on the medical field. In fact, it'd frankly be a waste of time for them during their study to learn about phages in any detail. The basic degree alone is already very long and full to the point of bursting. It'd be similar to expecting welders to understand the minutea of all states of matter, because TIG welding uses plasma to melt metal.
I don’t think it’s fair to say there is a lack of awareness that bacteriophages-as-concept exist. Most curricula in medical school will touch on these. However, what is more of a realistic lack of awareness is the ability to request bacteriophage therapy for a specific patient. It’s not something that has been thoroughly vetted or solved as a scalable solution because there’s a lot of technical hurdles. The closest approved therapy that is somewhat similar to what phage therapy would involve is CAR-T cell creation, and this is wildly expensive and resource intensive.
To give a somewhat comparable example, it’s more like someone saying asking why the average programmer doesn’t know anything about quantum computers as a solution for critical cryptographic problems.
To give a somewhat comparable example, it’s more like someone saying asking why the average programmer doesn’t know anything about quantum computers as a solution for critical cryptographic problems.
> I just can’t understand why it is like that.
My guess is because phage treatments are difficult or impossible to patent, and therefore unattractive to pharmaceutical companies. And pharmaceutical companies are incentivized to push their own treatments on doctors and hospitals.
My guess is because phage treatments are difficult or impossible to patent, and therefore unattractive to pharmaceutical companies. And pharmaceutical companies are incentivized to push their own treatments on doctors and hospitals.
I can suppose that economic incentives don’t align for its availability in the field but it doesn’t account for the ignorance of the practitioners. Bacteriophages are almost always one of the first things mentioned when the inevitable futility of antibiotics is discussed.
I think it's like with quantum computers. Average programmer knows they are there, but also knows it's decades before they are usable for everyday stuff.
Another article that describes the same story with additional details: https://www.motherjones.com/environment/2018/05/the-best-vir...
One factor that will return once people start to panic is table manners, many of which seem fussy (separate saving utensils, a butter knife, not putting used utensils onto the table) but actually evolved for hygiene reasons.
Sadly of course like any complex behavior it was also hijacked for sumptuary purposes (grape shears, egg spoons, not finishing your plate in some cultures) but I hold out a hope (probably in vail) that those kinds of rules won't be revived.
Sadly of course like any complex behavior it was also hijacked for sumptuary purposes (grape shears, egg spoons, not finishing your plate in some cultures) but I hold out a hope (probably in vail) that those kinds of rules won't be revived.
> One factor that will return once people start to panic is table manners, many of which seem fussy (separate serving utensils, a butter knife, not putting used utensils onto the table) but actually evolved for hygiene reasons.
When I was a kid growing up in the late 1950s, I thought we had this problem solved.
All the local restaurants kept a jar of mustard and a jar of mayonnaise on each table. (Yes, mayo sitting out all day, but let's ignore that for now.)
They didn't have separate utensils for these jars, you just used the table knife from your place setting. This led to a problem.
What if you had already cut your burger in half and then decided you want more mayo or mustard? You certainly wouldn't use a dirty table knife that would get bits of lettuce and tomato and bread and beef into the condiments.
Fortunately, my mom taught us basic sanitation: before you dip your table knife into the mustard or mayo jar, you must first lick it clean!
When I was a kid growing up in the late 1950s, I thought we had this problem solved.
All the local restaurants kept a jar of mustard and a jar of mayonnaise on each table. (Yes, mayo sitting out all day, but let's ignore that for now.)
They didn't have separate utensils for these jars, you just used the table knife from your place setting. This led to a problem.
What if you had already cut your burger in half and then decided you want more mayo or mustard? You certainly wouldn't use a dirty table knife that would get bits of lettuce and tomato and bread and beef into the condiments.
Fortunately, my mom taught us basic sanitation: before you dip your table knife into the mustard or mayo jar, you must first lick it clean!
Having silverware actually made out of silver existed for sanitary reasons as well. Same reason to throw a silver dollar in your well.
Unfortunately, it's also a cause of metal poisoning. "Blue blood" was a term for upper class families with silverware who had silver poisoning because of it.
My recollection: we don't know how to treat silver poisoning.
My recollection: we don't know how to treat silver poisoning.
its my understanding that "Blue blood" comes from the fact that most of them were pale and you can really see their blue veins, not that they were all poisoned by their silverware.
its my understanding that silverware is very safe, and getting silver poisoning from eating off it is extremely unlikely. they'd have to be eating their silverware to notice any difference
its my understanding that silverware is very safe, and getting silver poisoning from eating off it is extremely unlikely. they'd have to be eating their silverware to notice any difference
The term “blue blood” came to be associated with the aristocracy simply because it was not uncommon in earlier times for European nobility to have skin that appeared to have a blue cast. The bluish (or sometimes greenish) discoloration of their skin was often caused by a condition known as Argyria.
Argyria it the result of ingested silver particles that are not able to pass through the body. Historically, this was caused by particles from silver eating utensils being swallowed along with food or silver being taken for medicinal purposes. Aristocrats were originally the ones who could afford medicine and who enjoyed the daily privilege of eating off of silver plates, drinking from silver vessels, and, as the saying goes, being born with “a silver spoon in their mouth.” Thus, Argyria was a condition that was more common among the upper class.
http://www.sensationalcolor.com/color-meaning/color-words-ph...
Argyria it the result of ingested silver particles that are not able to pass through the body. Historically, this was caused by particles from silver eating utensils being swallowed along with food or silver being taken for medicinal purposes. Aristocrats were originally the ones who could afford medicine and who enjoyed the daily privilege of eating off of silver plates, drinking from silver vessels, and, as the saying goes, being born with “a silver spoon in their mouth.” Thus, Argyria was a condition that was more common among the upper class.
http://www.sensationalcolor.com/color-meaning/color-words-ph...
If this is true, why doesn't it show up in paintings? Your source is written by a "color expert", not a historian, and she cites no evidence. The veins showing through pale skin theory sounds more likely to me.
Paintings were very expensive, upper class commodities. They frequently idealized their subjects.
One British king had portraits delivered to him of a potential mate and was disappointed when she showed up and wasn't as attractive as her portrait. One source mocked him for it, saying he should have realized it was probably idealized, after all, it was his own portrait artist he sent, a guy who had been making him look good for years.
Colloidal silver still sometimes causes blue skin:
https://supplementpolice.com/colloidal-silver/
See also: https://en.m.wikipedia.org/wiki/Argyria
One British king had portraits delivered to him of a potential mate and was disappointed when she showed up and wasn't as attractive as her portrait. One source mocked him for it, saying he should have realized it was probably idealized, after all, it was his own portrait artist he sent, a guy who had been making him look good for years.
Colloidal silver still sometimes causes blue skin:
https://supplementpolice.com/colloidal-silver/
See also: https://en.m.wikipedia.org/wiki/Argyria
"While silver is potentially toxic to humans at high doses, the risk of serious harm from low doses, given over a short term, is slight". If something does no identifiable harm, and is a sign of high social class, wouldn't "idealizing" mean exaggerating argyria, not hiding it?
Everyone here, including you, is dismissing the idea that it's actually harmful. Maybe the people who made those paintings didn't see it that way.
"Born with a silver spoon in their mouth" is not usually a nice thing to say. It usually means they are basically overprivileged assholes.
In chelation groups, metal poisoning is generally viewed as having a negative impact on the personality. Perhaps people who routinely dealt with "blue bloods" had enough first-hand experience to notice that visible signs of silver poisoning correlated to asshole behavior.
Anyway, I don't actually think the questions being put to me are in good faith from people sincerely curious about my knowledge or my opinions. I think the pattern of downvotes and questions suggests everyone here thinks I'm a clueless idiot and they are trying to politely let me know how stupid I am because civility is demanded by the rules of the forum.
So continuing to try to answer questions in good faith is likely making me look stubborn, pigheaded, difficult and so much of a nutjob that there is no hope of reaching me.
It's not a dance I care to engage in further.
Adieu.
"Born with a silver spoon in their mouth" is not usually a nice thing to say. It usually means they are basically overprivileged assholes.
In chelation groups, metal poisoning is generally viewed as having a negative impact on the personality. Perhaps people who routinely dealt with "blue bloods" had enough first-hand experience to notice that visible signs of silver poisoning correlated to asshole behavior.
Anyway, I don't actually think the questions being put to me are in good faith from people sincerely curious about my knowledge or my opinions. I think the pattern of downvotes and questions suggests everyone here thinks I'm a clueless idiot and they are trying to politely let me know how stupid I am because civility is demanded by the rules of the forum.
So continuing to try to answer questions in good faith is likely making me look stubborn, pigheaded, difficult and so much of a nutjob that there is no hope of reaching me.
It's not a dance I care to engage in further.
Adieu.
>"Born with a silver spoon in their mouth" is not usually a nice thing to say. It usually means they are basically overprivileged assholes.
The concept of "overpriviledge" is modern.
The concept of "overpriviledge" is modern.
The one person I know who probably has argyria has dark-grey skin with a very slightly bluish tint.
It derives from middle ages Spanish racism. Visible veins to show their fine white skinned blood wasn't contaminated by the dark skinned Moors.
The Moors occupied territory in parts of what is now Spain and Portugal for nearly a thousand years.
The Moors occupied territory in parts of what is now Spain and Portugal for nearly a thousand years.
Silver is antimicrobial even at concentrations too low to be dangerous to humans. The same is true of copper.
https://en.wikipedia.org/wiki/Oligodynamic_effect
https://en.wikipedia.org/wiki/Oligodynamic_effect
Yes, both silver and copper are antimicrobial. As far as I know, silver has zero nutritional value. Copper is a micronutrient useful to humans.
If you want antimicrobial metal kitchenware, copper makes more sense than silver, though it should still not be overused.
Additionally, copper surfaces in hospitals have a proven track record of helping to kill infection and reduce the transmission of hospital acquired infections.
If you can afford it (as it isn't cheap) and want to Prep for a post antibiotic world, copper fixtures of various sorts in your home would not be a bad idea.
https://www.the-hospitalist.org/hospitalist/article/125654/p...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561453/
If you want antimicrobial metal kitchenware, copper makes more sense than silver, though it should still not be overused.
Additionally, copper surfaces in hospitals have a proven track record of helping to kill infection and reduce the transmission of hospital acquired infections.
If you can afford it (as it isn't cheap) and want to Prep for a post antibiotic world, copper fixtures of various sorts in your home would not be a bad idea.
https://www.the-hospitalist.org/hospitalist/article/125654/p...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561453/
BTW the conductivity of silver should make for an excellent frying pan. I saw one at Tiffanys but could not afford to find out.
AFAICT silver itself is not poisonous in any useful way - your skin might turn blue, and you'll metabolize certain compounds worse, but it won't kill you, or even slow you down much.
Now, if it was silver and arsenic, or some other toxic compound, that'd be a very bad time, but elemental silver shouldn't be any worse than mildly annoying.
Now, if it was silver and arsenic, or some other toxic compound, that'd be a very bad time, but elemental silver shouldn't be any worse than mildly annoying.
In Lionel Shriver’s wonderful ‘The Mandibles’ [0], set in the near-future, human contact has become a no-no for this reason. To touch is to spread germs, which are by now potentially deadly.
Great book if you’re in to near-future dystopia.
[0]: https://en.wikipedia.org/wiki/The_Mandibles
Great book if you’re in to near-future dystopia.
[0]: https://en.wikipedia.org/wiki/The_Mandibles
Will check it out! Sort of related in the no human contact sense is Asimov's The Naked Sun and (of course) E.M.Forster's The Machine Stops.
https://en.wikipedia.org/wiki/The_Naked_Sun https://en.wikipedia.org/wiki/The_Machine_Stops
https://en.wikipedia.org/wiki/The_Naked_Sun https://en.wikipedia.org/wiki/The_Machine_Stops
You complain about implements that could spread germs about, but also complain about grape shears that prevent everyone digging into the shared grapes with their bare hands.
What actually is the risk of inter person bacterial infection like this? Is there not more risk of getting ecoli from the shared salad, than the shared salad spoon?
What actually is the risk of inter person bacterial infection like this? Is there not more risk of getting ecoli from the shared salad, than the shared salad spoon?
I mean a regular set of shears works fine. A fish knife’s shape is handy for certain flakey fish (but not all fist, e.g. tuna, swordfish). Butter knife’s slight spatula shape is handy for butter transport but mainly serves to remind you “this isn’t yours” which always makes me laugh when I M issued one in the US.
I would settle for people not coughing an sneezing into their hands and then immediately touching everything in their vicinity. I see everyone around me doing this and it disgusts me.
(For the record, a better way to handle it is to sneeze into the inside of your elbow or immediately wash your hands after.)
(For the record, a better way to handle it is to sneeze into the inside of your elbow or immediately wash your hands after.)
It could be worse. Where I work, a few weeks ago I saw somebody lick his fingers and then reach into the container of forks and feel around for a while, apparently to find just the right fork.
I was guessing he had dry skin and had trouble picking up a fork unless he moistened his fingers first?
In any case I quietly went to a different container to get my own fork.
I was guessing he had dry skin and had trouble picking up a fork unless he moistened his fingers first?
In any case I quietly went to a different container to get my own fork.
I wouldn't go quietly but that's just me, fighting the windmills :).
> many of which seem fussy (separate saving utensils, a butter knife, not putting used utensils onto the table)
Fussy? Aren’t these just common sense? I wouldn’t consider them to even be “table manners”.
Fussy? Aren’t these just common sense? I wouldn’t consider them to even be “table manners”.
Looks like your comment is being downvoted due to lack of clarity in my note. My apologies!
Well yes, I agree they are sensible but it seems in the USA they are not only typically unknown but seen as pretentious.
E.g. rather than have a butter knife for transferring butter to your plate and then using a regular or smaller but regular style knife for spreading it on your bread, each person (in a typical semi-fancy US restaurant) is issued a butter knife which is used both to retrieve butter and to spread it on your (potentially bitten) bread.
And they are learned matters.
Well yes, I agree they are sensible but it seems in the USA they are not only typically unknown but seen as pretentious.
E.g. rather than have a butter knife for transferring butter to your plate and then using a regular or smaller but regular style knife for spreading it on your bread, each person (in a typical semi-fancy US restaurant) is issued a butter knife which is used both to retrieve butter and to spread it on your (potentially bitten) bread.
And they are learned matters.
> Looks like your comment is being downvoted due to lack of clarity in my note. My apologies!
I have more than enough karma to take a hit once in a while. No need to apologize :)
> it seems in the USA they are not only typically unknown but seen as pretentious
I live in the US, so I'm finding it surprising that you think these are not the norm. Perhaps I'm self-selecting the people I'm around, or don't pay attention to the people who do these things…
I have more than enough karma to take a hit once in a while. No need to apologize :)
> it seems in the USA they are not only typically unknown but seen as pretentious
I live in the US, so I'm finding it surprising that you think these are not the norm. Perhaps I'm self-selecting the people I'm around, or don't pay attention to the people who do these things…
Butter knives are used to prevent crumbs transfering to the butter dish, which can go mouldy. They've got nothing to do with germs in the mouth.
...for most superbugs, health departments and the US Centers for Disease Control and Prevention (CDC) don’t track who acquires them, nor do they know how many recovered or died. The most recent CDC report estimates that 23,000 people die in the U.S. each year from superbug infections, based on data from 2010. But a recent report estimated that at least 153,000 people died from superbug infections the same year, an estimate that is nearly seven-fold higher. We are allowing most superbugs to maintain their invisibility under the radar, where they are spreading quietly. Unreported. Undetected. And, increasingly, untreatable.
this isn't really scary at all. i'm not scared. are you scared? why be scared?
this isn't really scary at all. i'm not scared. are you scared? why be scared?
The point of her article wasn’t to push despair, but rather to urge the Western medical establishment to get moving on phage research.
Bacteriophages as a solution to our antibiotic resistance crisis have been largely ignored in the West due to unpatentability, research mainly performed in Eastern Europe, etc — but her story is that a bacteriophage cocktail saved her husband’s life where antibiotics failed...and the only reason they even were able to go that route was because she’s an epidemiologist who pulled some strings, pulled research teams together, got approvals, and managed the project herself.
Bacteriophages as a solution to our antibiotic resistance crisis have been largely ignored in the West due to unpatentability, research mainly performed in Eastern Europe, etc — but her story is that a bacteriophage cocktail saved her husband’s life where antibiotics failed...and the only reason they even were able to go that route was because she’s an epidemiologist who pulled some strings, pulled research teams together, got approvals, and managed the project herself.
Having seen her speak in person at IDWeek, I think an important thing to recognize is that the amount of work that went into treating her husband was pretty damned heroic - and it's not clear that that's not the standard for phage therapy.
I literally have a standard "Why phage are a problem", from the perspective of an infectious disease epidemiologist whose been super-interested in phage for like...a decade.
1) There's no such thing as a "broad spectrum" phage. They're organism specific, and that means not only would you need to keep a phage library on hand, but you'd have to do a lot of diagnostic tests. That's going to be both expensive and tricky. There are treatment guidelines for things like sepsis right now that are basically un-doable with phage therapy because of the time it takes to tune a phage library.
2) Phages are living things. Not only is that a weird regulatory framework to be in for a drug, but it also means that you need to be able to keep phage alive. In contrast, antibiotics are inert.
3) Phage therapy is also relatively new in the West, which means there's just less of a R&D infrastructure behind it.
There have been people working on commercializing phage therapy since I was in undergrad (I'm now a tenure-track professor). The problem is it's hard, and antibiotics are so much better as a treatment that there's kind of a ceiling on the excitement that they can generate.
Also, I would like to note that phage therapy wasn't only ignored due to unpatentability. A couple other reasons:
1) Antibiotics were superior in basically every respect. It's hard to justify decades of sustaining research into the fussy, expensive, edge-case alternative to something that works amazingly well.
2) Phage therapy was used in the West. Due to the technology at the time, it had a tendency to, well, kill people, due to contamination with bacterial endotoxins.
3) It's not clear phage can be turned into anything other than a pretty bespoke, custom tailored product. Even in the East it's not doable "at scale" in the way we talk about antibiotics.
I literally have a standard "Why phage are a problem", from the perspective of an infectious disease epidemiologist whose been super-interested in phage for like...a decade.
1) There's no such thing as a "broad spectrum" phage. They're organism specific, and that means not only would you need to keep a phage library on hand, but you'd have to do a lot of diagnostic tests. That's going to be both expensive and tricky. There are treatment guidelines for things like sepsis right now that are basically un-doable with phage therapy because of the time it takes to tune a phage library.
2) Phages are living things. Not only is that a weird regulatory framework to be in for a drug, but it also means that you need to be able to keep phage alive. In contrast, antibiotics are inert.
3) Phage therapy is also relatively new in the West, which means there's just less of a R&D infrastructure behind it.
There have been people working on commercializing phage therapy since I was in undergrad (I'm now a tenure-track professor). The problem is it's hard, and antibiotics are so much better as a treatment that there's kind of a ceiling on the excitement that they can generate.
Also, I would like to note that phage therapy wasn't only ignored due to unpatentability. A couple other reasons:
1) Antibiotics were superior in basically every respect. It's hard to justify decades of sustaining research into the fussy, expensive, edge-case alternative to something that works amazingly well.
2) Phage therapy was used in the West. Due to the technology at the time, it had a tendency to, well, kill people, due to contamination with bacterial endotoxins.
3) It's not clear phage can be turned into anything other than a pretty bespoke, custom tailored product. Even in the East it's not doable "at scale" in the way we talk about antibiotics.
As the author of the op-ed you are referring to, allow me to chime in. It's true that a huge effort went into saving my husband's life with phage therapy but as a result of that, it's getting easier to treat other cases. I'll comment on your other points too:
1) Broad spectrum phages don't exist in nature but gene-editing techniques can be applied and this technology now exists. Several biotechs are now working in this space.
2) Phages are not hard to keep 'alive'. They need to be refrigerated and kept away from sunlight.
3) True that phage therapy is relatively new in the West but the field is exploding. There are very few pharmas still developing antibiotics and very few in the pipeline, esp for gram-negatives, so there is an imperative to have alternatives to antibiotics.
With an ever-expanding phage library of well characterized phages, it is possible to generate personalized phage cocktails in days. An antibiotic takes a decade to develop, at around a billion $, and has collateral damage on the microbiome. For more on the story, check out ThePerfectPredator.com
1) Broad spectrum phages don't exist in nature but gene-editing techniques can be applied and this technology now exists. Several biotechs are now working in this space.
2) Phages are not hard to keep 'alive'. They need to be refrigerated and kept away from sunlight.
3) True that phage therapy is relatively new in the West but the field is exploding. There are very few pharmas still developing antibiotics and very few in the pipeline, esp for gram-negatives, so there is an imperative to have alternatives to antibiotics.
With an ever-expanding phage library of well characterized phages, it is possible to generate personalized phage cocktails in days. An antibiotic takes a decade to develop, at around a billion $, and has collateral damage on the microbiome. For more on the story, check out ThePerfectPredator.com
For the record, your talk at IDWeek last year was one of the highlights of the conference.
To touch on a few of your points:
1) I'm hopeful about these, and have been sort of idly following them, but I think they're a long way from anywhere close to the utility the average HackerNews reader is hoping to get out of them.
2) When compared to "There's an inert, shelf-and-temperature stable blister pack of these living at the bottom of a bag" they're hard to keep alive.
While not relevant in your husband's case, the vast burden of AMR is going to end up falling on the global poor, and in those cases, solutions that require a cold chain aren't reliable solutions.
3) It is exploding, but I've been following phage research for 15 years now, and it's one of those technologies that has lived in the "any day now" space that whole time. So I tend to try to temper the expectation of folks because I fear that it's going to end up, at best, as a supplemental solution to a very complex problem, rather than the "a new technology will get us out of this" path the popular media sometimes portrays it as.
To touch on a few of your points:
1) I'm hopeful about these, and have been sort of idly following them, but I think they're a long way from anywhere close to the utility the average HackerNews reader is hoping to get out of them.
2) When compared to "There's an inert, shelf-and-temperature stable blister pack of these living at the bottom of a bag" they're hard to keep alive.
While not relevant in your husband's case, the vast burden of AMR is going to end up falling on the global poor, and in those cases, solutions that require a cold chain aren't reliable solutions.
3) It is exploding, but I've been following phage research for 15 years now, and it's one of those technologies that has lived in the "any day now" space that whole time. So I tend to try to temper the expectation of folks because I fear that it's going to end up, at best, as a supplemental solution to a very complex problem, rather than the "a new technology will get us out of this" path the popular media sometimes portrays it as.
Are you saying there might be some survivor bias in this article?
Maybe 100 other equally qualified spouses tried equally ambitious programs to save someone, they all died, and we never heard about it...
Maybe 100 other equally qualified spouses tried equally ambitious programs to save someone, they all died, and we never heard about it...
Not necessarily as much as...
Right now, antibiotics are a point-and-shoot, frontline treatment for things, and phage therapy is a sort of "treatment of last resort" bespoke therapy.
Are phage super-useful for cases like the one in the article, where you have something super-resistant like Acinetobacter? Yes.
Is there much hope, near term, that they'll work as a drop-in replacement for the antibiotics we're losing? No.
Right now, antibiotics are a point-and-shoot, frontline treatment for things, and phage therapy is a sort of "treatment of last resort" bespoke therapy.
Are phage super-useful for cases like the one in the article, where you have something super-resistant like Acinetobacter? Yes.
Is there much hope, near term, that they'll work as a drop-in replacement for the antibiotics we're losing? No.
Agree!
I've heard that phages have a narrow target. They are not broad spectrum like antibiotics. Most of the time you don't know they exact bacteria that is causing the infection and to figure out may take days.
This is the major problem, in my view, with phage. You cannot treat until you've not only diagnosed the infection, but tuned the phage library being used. That's slow, even at major hospitals, and a major problem in places where diagnostic availability is limited.
From the article:
Alternatives to antibiotics are desperately needed.
She's not pushing phage research per se, just research into alternatives generally.
Alternatives to antibiotics are desperately needed.
She's not pushing phage research per se, just research into alternatives generally.
Did you stop reading there, by chance?
Shame on whoever downvoted you. The full last 5 paragraphs are devoted to bacteriophages, which are what ultimately saved the author's husband. The author is "Co-Director of the Center for Innovative Phage Applications and Therapeutics" at UCSD (https://profiles.ucsd.edu/steffanie.strathdee)
It closes on
"The possibility of living in a post-antibiotic era where simple surgeries or scrapes could lead to an infection that requires limb amputation or results in death means we need to improve AMR surveillance, diagnosis and treatment. This includes antibiotics, but should also include phage therapy. We can’t afford to bury a promising alternative to antibiotics for another hundred years."
She is absolutely pushing phage research. Not exclusive to any alternatives, but that is basically the point of the article.
It closes on
"The possibility of living in a post-antibiotic era where simple surgeries or scrapes could lead to an infection that requires limb amputation or results in death means we need to improve AMR surveillance, diagnosis and treatment. This includes antibiotics, but should also include phage therapy. We can’t afford to bury a promising alternative to antibiotics for another hundred years."
She is absolutely pushing phage research. Not exclusive to any alternatives, but that is basically the point of the article.
[deleted]
To me, the really scary thing about antibiotic resistance is not necessarily random infections in the hospital (as bad as that is) but the fact that antibiotics are what made surgery possible, and if they don’t work, all these medical procedures we’ve gotten used to as harmless suddenly carry a very serious risk-reward tradeoff. Imagine C-sections, biopsies, hip replacements, etc. all having a one-in-four chance of death. That’s what we’re heading back to.
For operations, sterilizations are carried out with a mixture of means like chemical disinfectants, subjecting instruments to extreme heat (Autoclaving), etc. but they don't rely on antibiotics. Instruments can be put into environments toxic to both human and bacterial cells. The big difference of antibiotics is that they are toxic to bacteria but not to human cells so they can be put directly into the system. Some bacteria are also developing resistance against chemical disinfectants but here we have a much larger choice.
It's defense in depth.
Yes, sterile technique is used to minimize the occurrence of surgical site infections. Sterile technique, when performed 100% correctly, isn't perfect and prophylactic antibiotics are standard to help mitigate any remaining risk.
Yes, sterile technique is used to minimize the occurrence of surgical site infections. Sterile technique, when performed 100% correctly, isn't perfect and prophylactic antibiotics are standard to help mitigate any remaining risk.
agree. and my next fear is that all of the medical establishment, suppliers, and practitioners who depend upon surgical procedures for their profitability downplay the additional risks and continue to encourage all of us to undergo surgery
Surgeons are already the bane of many infection control specialists.
Extremely scared, especially in light of barriers to drug approval killing off interest in antibiotics development. Just take a look at what happened to Achaogen: http://www.bioworld.com/perspectives/2019/04/24/a-decade-of-...
The FDA granted Fast Track designation for their antibiotic, only later refuse to approve it for use in bloodstream infections due to quibbling over study size (which was admittedly smaller than it could have been, largely in part due to the Fast Track designation). The antibiotic has been relegated to on-label use for complicated UTIs. Though it can still be used off-label, this isn't enough to attract further investment or keep sales strong enough to sustain ongoing operations. Achaogen was forced to lay off nearly all staff, and is now entering bankruptcy.
Unfortunately, this sort of thing is hardly unique among early stage pharma companies focusing on antibiotics, and it's steering investors away from such companies. It's also driving pharma professionals away.
The FDA granted Fast Track designation for their antibiotic, only later refuse to approve it for use in bloodstream infections due to quibbling over study size (which was admittedly smaller than it could have been, largely in part due to the Fast Track designation). The antibiotic has been relegated to on-label use for complicated UTIs. Though it can still be used off-label, this isn't enough to attract further investment or keep sales strong enough to sustain ongoing operations. Achaogen was forced to lay off nearly all staff, and is now entering bankruptcy.
Unfortunately, this sort of thing is hardly unique among early stage pharma companies focusing on antibiotics, and it's steering investors away from such companies. It's also driving pharma professionals away.
But they could still get approval in other countries.
As I understand it, other countries are not very profitable as pharmaceutical markets, so they probably won't get developed in the first place there.
Wouldn't have mattered previously, won't matter going forward. The USA is the most important and lucrative market, whether we like it or not.
Not scary at all. This is just life, and we must endure it.
Keep in mind at the same time this is happening we also have to deal with climate change and not blowing ourselves up in all out Nuclear War. And even if we avoid all that you could still step outside and be shot or stabbed by a ruffian who leaves you dead all the same.
Keep in mind at the same time this is happening we also have to deal with climate change and not blowing ourselves up in all out Nuclear War. And even if we avoid all that you could still step outside and be shot or stabbed by a ruffian who leaves you dead all the same.
Any recommendations on what an individual could do to help? Organizations to donate to? Challenges that could be tackled by a startup? Promising companies to consider investing in?
Also, can anybody explain why the CDC doesn’t mandate reporting?
Also, can anybody explain why the CDC doesn’t mandate reporting?
I'm having trouble figuring out how to reply to the way you are framing the problem space.
There are several Einstein quotes along the lines of "A problem cannot be solved using the same thinking that created it."
The problem of antibiotic resistance won't be solved with the same mindset that got us here.
One thing contributing to the rise of antibiotic resistance is poor santitation in developing countries. Another is poverty.
There is also research into how to break up biofilm and thereby reverse antibiotic resistance. It points to issues with body chemistry which can basically be tied to diet.
I think there are clearly avenues we can pursue, but most people are extremely dismissive of those avenues. So they simply aren't being pursued in earnest.
There are several Einstein quotes along the lines of "A problem cannot be solved using the same thinking that created it."
The problem of antibiotic resistance won't be solved with the same mindset that got us here.
One thing contributing to the rise of antibiotic resistance is poor santitation in developing countries. Another is poverty.
There is also research into how to break up biofilm and thereby reverse antibiotic resistance. It points to issues with body chemistry which can basically be tied to diet.
I think there are clearly avenues we can pursue, but most people are extremely dismissive of those avenues. So they simply aren't being pursued in earnest.
"One thing contributing to the rise of antibiotic resistance is poor santitation in developing countries. Another is poverty."
I assume this is why you were getting downvotes? I was going to too, but it does actually check out.
https://www.omicsonline.org/open-access/antibiotic-abuse-in-...
I assume this is why you were getting downvotes? I was going to too, but it does actually check out.
https://www.omicsonline.org/open-access/antibiotic-abuse-in-...
The very article we are discussing talks about a man getting an antibiotic resistant infection in Egypt, then being flown to Germany and eventually the US with the infection still unresolved. It terms it "Iraqibacter" and gives a brief origin of this class of microbes as starting in the Middle East and being exported to Europe and America.
So if that line you quoted is getting me downvotes, then everyone downvoting me has failed basic reading comprehension.
I have read other things that state more directly that we breed antibiotic resistant infections in less developed countries, no reading between the lines required.
But I have also read up on research into stunting. It has pertinent findings about lack of sanitation fostering low grade chronic infections that basically cause failure to thrive that isn't readily resolvable because the problem isn't rooted in the individual. It is rooted in the lack of sanitation of a larger area.
Sources:
The right gut microbes help infants grow
http://www.sciencemag.org/news/2016/02/right-gut-microbes-he...
What causes stunting?
https://borgenproject.org/what-causes-stunting/
Beyond Malnutrition: The Role of Sanitation in Stunted Growth
https://ehp.niehs.nih.gov/doi/10.1289/ehp.122-A298
Pertinent quotes from that last article:
In countries such as India, for instance, stunting occurs even among well-fed children, and that’s led investigators to consider other causes, especially poor sanitation and hygiene. Evidence shows that children who live without adequate sanitation, hygiene, and clean drinking water don’t grow as well as children who do.
In somewhat newer thinking, researchers are exploring the possibility that poor hygiene and a lack of sanitation induce a gut disorder called environmental enteropathy (EE) that diverts energy from growth toward an ongoing fight against subclinical infection.
So if that line you quoted is getting me downvotes, then everyone downvoting me has failed basic reading comprehension.
I have read other things that state more directly that we breed antibiotic resistant infections in less developed countries, no reading between the lines required.
But I have also read up on research into stunting. It has pertinent findings about lack of sanitation fostering low grade chronic infections that basically cause failure to thrive that isn't readily resolvable because the problem isn't rooted in the individual. It is rooted in the lack of sanitation of a larger area.
Sources:
The right gut microbes help infants grow
http://www.sciencemag.org/news/2016/02/right-gut-microbes-he...
What causes stunting?
https://borgenproject.org/what-causes-stunting/
Beyond Malnutrition: The Role of Sanitation in Stunted Growth
https://ehp.niehs.nih.gov/doi/10.1289/ehp.122-A298
Pertinent quotes from that last article:
In countries such as India, for instance, stunting occurs even among well-fed children, and that’s led investigators to consider other causes, especially poor sanitation and hygiene. Evidence shows that children who live without adequate sanitation, hygiene, and clean drinking water don’t grow as well as children who do.
In somewhat newer thinking, researchers are exploring the possibility that poor hygiene and a lack of sanitation induce a gut disorder called environmental enteropathy (EE) that diverts energy from growth toward an ongoing fight against subclinical infection.
The quoted comment could read as just blaming poorer people etc, which is how I read it at first, after further digging the comment seems justified. Reading your comment I can't see another reason for the downvote, and antibiotic resistance being more common in developing nations wasn't something I was that aware of, so I was confirming to others you aren't being racist or anything.
Maybe they should have done their own research? I don't know. The sample size of one in the article by itself doesn't justify the sweeping statement you made.
Ultimately and unfortunately people will say unsubstantiated and unpleasant things and some reasonable comments get caught in people's 'spam filter'.
Maybe they should have done their own research? I don't know. The sample size of one in the article by itself doesn't justify the sweeping statement you made.
Ultimately and unfortunately people will say unsubstantiated and unpleasant things and some reasonable comments get caught in people's 'spam filter'.
It is not a sample size of one. She gave the history of a thing common enough to have a nickname.
so I was confirming to others you aren't being racist or anything.
Thank you.
so I was confirming to others you aren't being racist or anything.
Thank you.
Pressure large meat companies to not buy from farms that use routine antibiotics. That's probably the biggest practical thing.
It worked for hormones (do you see much BST cow milk)?
The next thing is convincing India to stop handing out antibiotics like candy, but that's not something an individual can do.
It worked for hormones (do you see much BST cow milk)?
The next thing is convincing India to stop handing out antibiotics like candy, but that's not something an individual can do.
"Also, can anybody explain why the CDC doesn’t mandate reporting?"
Because a great deal of this is done at the state level. Working on these kind of problems, there's a very difficult balance of reporting requirements, agreed upon definitions (especially not just what you have but where you got it), various stakeholders, etc.
And the CDC collects a lot of data even if things are universally reportable. And there's a lot of ongoing improvement.
Because a great deal of this is done at the state level. Working on these kind of problems, there's a very difficult balance of reporting requirements, agreed upon definitions (especially not just what you have but where you got it), various stakeholders, etc.
And the CDC collects a lot of data even if things are universally reportable. And there's a lot of ongoing improvement.
[deleted]
Call your members of congress and demand that they ask the CDC that question.
Antibiotic company stocks have been decimated in the last couple of years so if you feel adventurous and prepared to lose your savings, this is a great time to buy.
What are some example companies/symbols?
NASDAQ: MLNT
OTCMKTS: AKAOQ
Read here for more info: https://www.bloomberg.com/news/articles/2019-05-03/antibioti...
OTCMKTS: AKAOQ
Read here for more info: https://www.bloomberg.com/news/articles/2019-05-03/antibioti...
I'm russian. And for me this article sounds completely idiotic - phage research was always ongoing in SU and literally everyone is aware of the alternative to antibiotics. At the moment there are lab networks available across all the modern russia where you may take a test and find a best phage to your bacterias. One of several mass-produced phages.
Moreover, if you dig into soviet medicine, you may find several awesome things. At the moment there are _two_ widely available st.aureus vaccines in russia. For those who work with farm animals. These vaccines may be used for both prevention and treatment. I've used them for myself to treat multiple-antibiotic resistant st.aureus infection and got rid of it.
The other interesting thing is a synhetic analogue of thymopoietin - an incredible immune stimulant which may in multiple cases help you to deal with an infection without antibiotics.
Unfortunately, russian doctors are idiots and russian medicine is almost dead and noone is interested in any stuff from there.
I, personally, regret that we didn't hear any news about epimerox - that only substance would solve 80% of our problems with bacterias, including multi-resistent ones.
Moreover, if you dig into soviet medicine, you may find several awesome things. At the moment there are _two_ widely available st.aureus vaccines in russia. For those who work with farm animals. These vaccines may be used for both prevention and treatment. I've used them for myself to treat multiple-antibiotic resistant st.aureus infection and got rid of it.
The other interesting thing is a synhetic analogue of thymopoietin - an incredible immune stimulant which may in multiple cases help you to deal with an infection without antibiotics.
Unfortunately, russian doctors are idiots and russian medicine is almost dead and noone is interested in any stuff from there.
I, personally, regret that we didn't hear any news about epimerox - that only substance would solve 80% of our problems with bacterias, including multi-resistent ones.
Is it possible to order some to the EU? I'm having unfortunate combination of staph infection+ ciprofloxacin intolerance.
I guess it's not. But you may ask a russian pharmacy to prepare two boxes for you then visit the country and pick the order. The names in russian are: "антифагин стафилококковый" and "анатоксин стафилококковый очищенный адсорбированный". In case you decide go this way I would suggest you to use second one according to "blood donor" scheme (3 shots of 2ml, one ml into each shoulderblade, with 2 week intervals) and increase all dosages for the first one for 0.2ml (so, ten shot in ten days, one shot each day, starting from 0.3ml and ending with 1.2). You may use insulin syringe for first one, for second one you would need some assistance and usual syringe but in worst case you may use insulin one too.
Disclaimer: consult your doctor first, it's just a random advice from internets, blah-blah.
Disclaimer: consult your doctor first, it's just a random advice from internets, blah-blah.
These things (st. vaccinces) are mostly unknown to usual russian doctors, they are produced for farm workers. A typical therapist wouldn't prescribe you that stuff - they are not aware of their existence. Again - russians doctors are idiots, but there is some amazing soviet legacy you may greatly benefit from. And you don't _really_ need a prescription to buy the stuff.
[deleted]
I wish there were a nanotechnology startup that would address MRSA. In theory, you can develop nanobots that attack specific types of bacteria. Not sure if this would work:
https://www.youtube.com/watch?v=5bQhGS8V6dQ
https://www.youtube.com/watch?v=5bQhGS8V6dQ
You don't need nanorobots.
You may just pick old soviet vaccines and resolve this particular problem (see my other post in this topic).
Also there are a lot of great antibiotics (see epimerox) which still aren't on the market because of many different reasons.
You may just pick old soviet vaccines and resolve this particular problem (see my other post in this topic).
Also there are a lot of great antibiotics (see epimerox) which still aren't on the market because of many different reasons.
Startups are not the answer to everything... Capitalism and healthcare do not go well together because you profit from negative health.
Is it possible to establish a living will with her organization?
I would love to have a hotline my next of kin can call to begin treatment whether or not my doctors are aware of its availability.
I would love to have a hotline my next of kin can call to begin treatment whether or not my doctors are aware of its availability.
Why aren’t all hospital surfaces coated with silver?
There's a lot of work in working antimicrobial sufaces - silver, copper, some interesting structural patterns, etc.
The problem is it's not particularly clear they work, and they are very expensive, and often a pain to clean.
The problem is it's not particularly clear they work, and they are very expensive, and often a pain to clean.
https://en.wikipedia.org/wiki/Argyria perhaps?
And expense. Of course.
And expense. Of course.
Better yet, why don't we have mobile hospital units. Rather than bringing all the sick people and disease into one place, why not go to the place of sickness. Perhaps it's economically not feasible, but I've always it made more sense.
Brass will do quite well and is a lot cheaper.
It's not just antibiotics, but some types of vaccines are creating evolutionary pressure and new strains of the pathogen. E.g. for pertussis
> it is thought that B. pertussis is adapting under acellular vaccine mediated immune selection pressure, towards vaccine escape [1]
> an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetellapertussis variants that are better able to evade vaccine-mediated immunity than older isolates [2]
[1] https://academic.oup.com/femspd/article/73/8/ftv064/2467598
[2] https://www.sciencedirect.com/science/article/pii/S156713481...
> it is thought that B. pertussis is adapting under acellular vaccine mediated immune selection pressure, towards vaccine escape [1]
> an increase in asymptomatic infection with concomitant increases in transmission and increased selection pressure for Bordetellapertussis variants that are better able to evade vaccine-mediated immunity than older isolates [2]
[1] https://academic.oup.com/femspd/article/73/8/ftv064/2467598
[2] https://www.sciencedirect.com/science/article/pii/S156713481...
>> some types of vaccines are creating evolutionary pressure...
Wouldn't it be nice if we had more eradication programs? Evolution is going to work around every vaccine eventually unless we eradicate the disease. Yes, this is a hard problem but I think long term its worth it. Eventually we might get good at it.
Wouldn't it be nice if we had more eradication programs? Evolution is going to work around every vaccine eventually unless we eradicate the disease. Yes, this is a hard problem but I think long term its worth it. Eventually we might get good at it.
I don't believe that eradication is possible, but I'm curious to hear more what your thoughts are
Smallpox is a counterexample to your concern.
Polio almost is, the issues are social and political and have little to do with vaccine escape.
Polio almost is, the issues are social and political and have little to do with vaccine escape.
Any disease that only affects humans can be eradicated with a universal vaccine.
If it lives on in other species, it's a much harder problem.
If it lives on in other species, it's a much harder problem.
Eradication is absolutely possible. High enough vaccination rates would help prevent further evolution of viruses, eventually containing them and then removing them provided there aren't alternative vectors like animals or pets.
Unfortunately, certain other efforts are compromising this.
Unfortunately, certain other efforts are compromising this.
It's not at all clear the pertussis vaccine creates a strong and lasting immunity enough to be an eradication target.
Honestly, it's not one of the more promising eradication targets.
Honestly, it's not one of the more promising eradication targets.
And people still wonder why civilized countries forbid prophilactic antibiotics usage in livestock....
[deleted]
This article yet again reports on the lack of awareness about bacteriophages in the medical community. I just can’t understand why it is like that. I, an idiot, have heard about it. How do people, who seemingly work with superbugs all the time and understand the threat, not know this thing that is amongst the very first things one is exposed to when one takes a superficial glance at the available literature?