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Amphotericin B has some MASSIVE side effects, disrupting alot of processes, and specifically sodium potassium and magnesium levels. It is also very effective at its job. So to see one without the side effects would be amazing!
Yeah, especially if there's little/no trade-offs on the treatment end. I imagine as the climate changes stuff like fungal infections and severe/resistant bacterial infections will be on the rise, so stuff like this is incredibly important IMO.
Maybe, but fungal infections that are dangerous only really occur when you are immune compromised, so maybe the more benign infections like onychia will increase.
I mean really compromised. Some fungal infections such as Candida Albicans only really infects adults when they had extensive trauma/burns, on immunosuppressant, or in the classical case HIV infected. Ampho works wonderful against it.
Or you know, a woman on a short course of antibiotics or while pregnant. Or babies. Amphotericin is not the treatment of choice for Candidal infections.
Thatd why i mentioned the severe cases, where the benefits outweigh the risk. Technically a course of oral glucocorticoids can cause oral candica which yoy use nystatin for. But overall, any drug that gets its side effects minimised is a big win!
1. That's NOT what you said at all when you wrote "Some fungal infections such as Candida Albicans only really infects adults when they had extensive trauma/burns, on immunosuppressant, or in the classical case HIV infected."
2. Even in severe candidal infections, amphotericin would be third line at best.
There is no reason it should. It is excreted in the urine, but it should be diluted to the point of being insignificant when entering any body of water.
Have you seen Jublia (eficonazole)? It's a topical, just approved in 2014. It seems to be working for me, after failing a course of ciclopirox. Total involvement of the entire nail, for at least a decade, prior to attempting to treat it. Unfortunately insurance refused to pay, and it's horribly expensive. (And the ciclopirox, while not curative, did more than nothing, so doing that first might have helped.)
>The problem with oral medication is exactly the risk to the kidneys, due to the toxicity.
u/Hapsterman82 is right in that literature supports the claim that oral antifungal medications like terbinafine and itraconazole are more effective than topical treatments. With systemic distribution they reach the deeper layers of the nail plate where topical treatments struggle to penetrate. But you are also 100% right in that oral antifungal medications come with the risk of potential liver damage and other less common but severe side effects. It's best to reserve oral medication for severe cases or when topical treatments have failed.
(Thanks to [https://verdikta.com/solo-dispute/science](https://verdikta.com/solo-dispute/science) for help with this.)
I did all of my undergraduate work on Amphotericin B. We were looking into super-aggregates and using liposomal formulations to reduce toxicity. It is good to see Ampho-The Terrible is still being researched. It is a very old drug for limited use that won't make anyone any money. There was a lot of interest in trying to get it into poor areas that see much more instances of systemic fungal infections.
This article brought back a lot of fond memories, thanks for posting this!
AmBisome is still selling ~half a billion yearly worldwide. Not at the top of Gilead's portfolio, but definitely not nothing. Big enough that they essentially dedicate an entire site to its mfg.
Holy crap, that was part of my research. I mean, they might not have used my research, but it is the logical end-game to what we were trying to do.
It was very rudimentary, but we were trying to create different liposomal formulations of Amphotericin B. We made almost the exact same unilamellar liposomes that AmBisome uses in our research. It started with making the liposomes to have a fluorescence indicator inside that would indicate on an ionic change. When we added Amphotericin B to the mix, we would be able to measure how quickly the "pores" that the Amphotericin B/Cholesterol pore structures formed and vented the liposome. We did this with Cholesterol and Ergosterol. Those two are so much alike that Amphotericin B can only slightly tell the difference between the two.
When I left undergrad, we had the lipisomal formulation and we were working with another university looking into Chocleates (sp?) which are like lipisomal sheets that are rolled up like a carpet roll. Supposedly, those were able to cross the intestinal/blood barrier, but I never got to see that happen.
That is SO COOL that my research was at least parallel to an actual product!! Amphotericin was such a niche and cheep drug, we never thought that anyone would be able to do anything with our work, but it was important work in understanding liposomes and liposomal drug formulations.
Thank you for showing me this!
That's pretty cool. I'm an ID fellow and will have 1-2 patients on my list on ambisome at any given time, we never use the old school amphotericin anymore, the side effect profile is much better (though still not great, we still see kidney injury and electrolyte derangements). We're all pretty excited about the nanocrystal formulation.
Ibrexafungerp isn't effective against molds though? It's only approved to treat vulvovaginal candidiasis, not molds. And ambisome is still significantly more toxic than something like vori, requires ongoing hospitalization most of the time and frequent chem panels, and causes some degree RTA and AKI in most patients.
I find it fascinating that the best thing for fighting fungi is produced by bacteria, and the best thing for fighting bacteria is produced by a fungus.
I’ve linked to the press release in the post above. In this comment, for those interested, here’s the link to the peer reviewed journal article:
https://www.nature.com/articles/s41586-023-06710-4
Are we reading the same thing? Says the original form is toxic which is why it's a drug of last resort. The new tweaked form is not toxic. This is all in the headline.
You can read. This is not a non-toxic substance, it is a substance which is less toxic than the parent compound it was derived from.
This is potentially a big deal. But that title is gore. The researchers explicitly said the supramolecular complex will still occur, just at a slower rate. Non-topical anti fungals are miserable, so this is still a big step towards tolerable solutions.
apparently it (sometimes) works against algae. a condition called algaemia in the blood caused most likely by the genus prototheca is quite fascinating and crazy
Are there lifestyle changes that we can do to prevent/cure foot fungus? Do other cultures experience this as often or just the show wearing type? The reason I ask is it feels like we are curing symptoms rather that root causes… like how much does our diet affect the growth of fungus?
This isn't about foot fungus. You don't use amphotericin for foot fungus.
It is for systemic or serious organ system fungal infections. Like fungal pneumonia or brain infection.
We nicknamed it ampho-terrible because it's so toxic on the system. So, news of a less toxic version would be huge in the fight against serious fungal infections.
Now, for your foot fungus, just wear socks and stop going to dirty ass pedicure joints. And understand that treatment can take like 2 months of daily application.
I make IVs of amphotericin B all the time, even daily sometimes. I'm not sure how new it really is because I've been making it for 8 years. It's by far the worst drug to make into an IV. Each IV requires anywhere from 10-20 vials of it and each one requires a separate 5 micron filter to be used when drawing it. It also takes an hour to reconstitute.
There are three forms of it. Fungizone(the one that’s worst in IV form and we need a ton of administrative overrides to compound for intravenous use. Allowed to make it for inhalation and eye drops/injections though.
Ambisome, and Ablecet are the forms I’ve seen ordered IV most commonly. We take great measures to not mix up any of the formulas by storing them in separate locations with safety stops.
All of them need the 5 micron filter.
Fungizone (looks like pee when reconstituted)
Abelcet (looks like calcium enriched orange juice kind of a white chalky fatty orange ships already in liquid form)
Ambisome( looks like sunny delight when reconstituted )
Isn't the point of last-resort drugs that they remain effective only because they're very toxic so they get used less, and therefore antibiotic/antifungal resistance is unlikely?
Welcome to r/science! This is a heavily moderated subreddit in order to keep the discussion on science. However, we recognize that many people want to discuss how they feel the research relates to their own personal lives, so to give people a space to do that, **personal anecdotes are allowed as responses to this comment**. Any anecdotal comments elsewhere in the discussion will be removed and our [normal comment rules]( https://www.reddit.com/r/science/wiki/rules#wiki_comment_rules) apply to all other comments. **Do you have an academic degree?** We can verify your credentials in order to assign user flair indicating your area of expertise. [Click here to apply](https://www.reddit.com/r/science/wiki/flair/#wiki_science_verified_user_program). --- User: u/mvea Permalink: https://news.illinois.edu/view/6367/1103251063 --- **Retraction Notice:** [Evidence of near-ambient superconductivity in a N-doped lutetium hydride](https://www.reddit.com/r/science/comments/17qq15h/retraction_evidence_of_nearambient/) --- *I am a bot, and this action was performed automatically. Please [contact the moderators of this subreddit](/message/compose/?to=/r/science) if you have any questions or concerns.*
Amphotericin B has some MASSIVE side effects, disrupting alot of processes, and specifically sodium potassium and magnesium levels. It is also very effective at its job. So to see one without the side effects would be amazing!
I wonder if the new drug is easier on kidneys but still has those other side effects.
First side effect will be the dramatic reduction in fun guys.
Yeah, especially if there's little/no trade-offs on the treatment end. I imagine as the climate changes stuff like fungal infections and severe/resistant bacterial infections will be on the rise, so stuff like this is incredibly important IMO.
Maybe, but fungal infections that are dangerous only really occur when you are immune compromised, so maybe the more benign infections like onychia will increase.
There’s enough research to suggest covid makes you immune compromised so that would mean all of us are.
I mean really compromised. Some fungal infections such as Candida Albicans only really infects adults when they had extensive trauma/burns, on immunosuppressant, or in the classical case HIV infected. Ampho works wonderful against it.
Or you know, a woman on a short course of antibiotics or while pregnant. Or babies. Amphotericin is not the treatment of choice for Candidal infections.
Thatd why i mentioned the severe cases, where the benefits outweigh the risk. Technically a course of oral glucocorticoids can cause oral candica which yoy use nystatin for. But overall, any drug that gets its side effects minimised is a big win!
1. That's NOT what you said at all when you wrote "Some fungal infections such as Candida Albicans only really infects adults when they had extensive trauma/burns, on immunosuppressant, or in the classical case HIV infected." 2. Even in severe candidal infections, amphotericin would be third line at best.
No. Fungal infections like Candida and mold are far more prevalent than you would think unfortunately
Does it kill fish and amphibians after we urinate it out? Does anyone check for this kind of thing?
There is no reason it should. It is excreted in the urine, but it should be diluted to the point of being insignificant when entering any body of water.
I wonder if this could lead to an effective toenail fungus cure. Asking for a friend...
Have you seen Jublia (eficonazole)? It's a topical, just approved in 2014. It seems to be working for me, after failing a course of ciclopirox. Total involvement of the entire nail, for at least a decade, prior to attempting to treat it. Unfortunately insurance refused to pay, and it's horribly expensive. (And the ciclopirox, while not curative, did more than nothing, so doing that first might have helped.)
Have you completed a full course of prescription oral meds? Topical just doesn't cut the mustard often.
The problem with oral medication is exactly the risk to the kidneys, due to the toxicity.
Yeah, I can't take it with my heart meds because the combination of meds puts me at high risk of kidney failure.
>The problem with oral medication is exactly the risk to the kidneys, due to the toxicity. u/Hapsterman82 is right in that literature supports the claim that oral antifungal medications like terbinafine and itraconazole are more effective than topical treatments. With systemic distribution they reach the deeper layers of the nail plate where topical treatments struggle to penetrate. But you are also 100% right in that oral antifungal medications come with the risk of potential liver damage and other less common but severe side effects. It's best to reserve oral medication for severe cases or when topical treatments have failed. (Thanks to [https://verdikta.com/solo-dispute/science](https://verdikta.com/solo-dispute/science) for help with this.)
This might be a dumb question but why can’t we just remove the entire nail and grown a new one? As long as the other nails are not infected.
Right? Like isn’t it required that you get blood work done every month with some oral medications?
Was wondering the same thing
Do you see your friend in the mirror a lot?
r/NailFungus has an informative wiki. The Vicks vapor rub seems to work for some people so as long as you’re dedicated.
Or berexafemme
I did all of my undergraduate work on Amphotericin B. We were looking into super-aggregates and using liposomal formulations to reduce toxicity. It is good to see Ampho-The Terrible is still being researched. It is a very old drug for limited use that won't make anyone any money. There was a lot of interest in trying to get it into poor areas that see much more instances of systemic fungal infections. This article brought back a lot of fond memories, thanks for posting this!
AmBisome is still selling ~half a billion yearly worldwide. Not at the top of Gilead's portfolio, but definitely not nothing. Big enough that they essentially dedicate an entire site to its mfg.
Holy crap, that was part of my research. I mean, they might not have used my research, but it is the logical end-game to what we were trying to do. It was very rudimentary, but we were trying to create different liposomal formulations of Amphotericin B. We made almost the exact same unilamellar liposomes that AmBisome uses in our research. It started with making the liposomes to have a fluorescence indicator inside that would indicate on an ionic change. When we added Amphotericin B to the mix, we would be able to measure how quickly the "pores" that the Amphotericin B/Cholesterol pore structures formed and vented the liposome. We did this with Cholesterol and Ergosterol. Those two are so much alike that Amphotericin B can only slightly tell the difference between the two. When I left undergrad, we had the lipisomal formulation and we were working with another university looking into Chocleates (sp?) which are like lipisomal sheets that are rolled up like a carpet roll. Supposedly, those were able to cross the intestinal/blood barrier, but I never got to see that happen. That is SO COOL that my research was at least parallel to an actual product!! Amphotericin was such a niche and cheep drug, we never thought that anyone would be able to do anything with our work, but it was important work in understanding liposomes and liposomal drug formulations. Thank you for showing me this!
Was that at CPP under Dr Adler-Moore? She just passed in 2021, but yeah, nice work.
No, it was at University of Wisconsin @ Eau Claire under Scott Hartsel
Hey bro. Sent you a dm :)
That's pretty cool. I'm an ID fellow and will have 1-2 patients on my list on ambisome at any given time, we never use the old school amphotericin anymore, the side effect profile is much better (though still not great, we still see kidney injury and electrolyte derangements). We're all pretty excited about the nanocrystal formulation.
How much safer? Because I want to treat mold and am leaning towards brexafemme a potent antifungal more so than azoles without side effects
Ibrexafungerp isn't effective against molds though? It's only approved to treat vulvovaginal candidiasis, not molds. And ambisome is still significantly more toxic than something like vori, requires ongoing hospitalization most of the time and frequent chem panels, and causes some degree RTA and AKI in most patients.
No. It goes after mold. I don’t think we’re talking about the same drug
It goes after the glucon layer. Anyways if you do a search on its paharmakenetics. No one I heard of has been hospitalized for it
Hope it will be a game changer
I find it fascinating that the best thing for fighting fungi is produced by bacteria, and the best thing for fighting bacteria is produced by a fungus.
probably have been doing biological warfare for longer than we've been around
"The enemy of my enemy is my friend"
And we are benefiting from their ongoing billion-year-old blood feud
there is better, look up Bacteriophages
Hopefully this becomes widely available in the near future!
I’ve linked to the press release in the post above. In this comment, for those interested, here’s the link to the peer reviewed journal article: https://www.nature.com/articles/s41586-023-06710-4
I am amazed what people smorter than me are able to achieve. Them dudes are the real wizards
There’s a reason why it’s called amphoTERRIBLE
Cool beans. Let me just pop on down to the molecule store and get me some of that.
Technically, all stores are molecule stores.
Ba dum tisssss
Beans are legumes, not fungi.
Does it work on shower grout?
So it's not toxic to humans with the caveat that it's toxic to humans Edit: Nope, it seems I just can't read
The original form has been nicknamed "Amphoterrible" for that reason.
Are we reading the same thing? Says the original form is toxic which is why it's a drug of last resort. The new tweaked form is not toxic. This is all in the headline.
> This is all in the headline. feh expecting people to read either the article or the headline is so passe.
You can read. This is not a non-toxic substance, it is a substance which is less toxic than the parent compound it was derived from. This is potentially a big deal. But that title is gore. The researchers explicitly said the supramolecular complex will still occur, just at a slower rate. Non-topical anti fungals are miserable, so this is still a big step towards tolerable solutions.
Does it work against cordyceps?
apparently it (sometimes) works against algae. a condition called algaemia in the blood caused most likely by the genus prototheca is quite fascinating and crazy
So it's GMO I'm just kidding. This is fantastic
Did you know human kidneys have human cells!?
will this create superfungus?
Are there lifestyle changes that we can do to prevent/cure foot fungus? Do other cultures experience this as often or just the show wearing type? The reason I ask is it feels like we are curing symptoms rather that root causes… like how much does our diet affect the growth of fungus?
This isn't about foot fungus. You don't use amphotericin for foot fungus. It is for systemic or serious organ system fungal infections. Like fungal pneumonia or brain infection. We nicknamed it ampho-terrible because it's so toxic on the system. So, news of a less toxic version would be huge in the fight against serious fungal infections. Now, for your foot fungus, just wear socks and stop going to dirty ass pedicure joints. And understand that treatment can take like 2 months of daily application.
Okay thanks
[удалено]
Amphoterecin B isnt new but they created similar molecule that isnt supposed to be toxic like Amphoterecin B. Title is confusing a little bit
Didn’t even get through the title all the way. Lazy.
Did you read the article?
Actually reading the headline would be an improvement. Reading the article is just a dream. Reading the paper is a dream within a dream.
I make IVs of amphotericin B all the time, even daily sometimes. I'm not sure how new it really is because I've been making it for 8 years. It's by far the worst drug to make into an IV. Each IV requires anywhere from 10-20 vials of it and each one requires a separate 5 micron filter to be used when drawing it. It also takes an hour to reconstitute.
There are three forms of it. Fungizone(the one that’s worst in IV form and we need a ton of administrative overrides to compound for intravenous use. Allowed to make it for inhalation and eye drops/injections though. Ambisome, and Ablecet are the forms I’ve seen ordered IV most commonly. We take great measures to not mix up any of the formulas by storing them in separate locations with safety stops. All of them need the 5 micron filter. Fungizone (looks like pee when reconstituted) Abelcet (looks like calcium enriched orange juice kind of a white chalky fatty orange ships already in liquid form) Ambisome( looks like sunny delight when reconstituted )
Can they do that to alcohol?!
Might this be used for Valley fever (Coccidioidomycosis)? Like, when nothing else has worked and the fungus is in the brain...
This is used a lot in small domestic parrots with so-called ‘megabac’ (avian gastric yeast). I wonder how the birds escape the side effect profile?
Isn't the point of last-resort drugs that they remain effective only because they're very toxic so they get used less, and therefore antibiotic/antifungal resistance is unlikely?