What precisely is the suggested mechanism by which agricultural anfifungals affect human pathogens?
Is it just that they select resistant fungi and we eat that?
Or is it that we eat leftover azoles and thus build up immunity?
High time to tackle drug-resistant fungal infections
31–40 of 47 posts
Re: High time to tackle drug-resistant fungal infections
#32Earlier quoted context omitted.
I don't think that's right. * There is limited evidence that farming use of antibiotics is what drives resistance in clinical cases. That is - we use enormous amounts of antibiotics in farming, but the resistance it creates doesn't really seem to move into the hospitals. * There is no reason to believe we've hit a wall and can't invent more antibiotics in the future. Historically we haven't focused much on antibiotic…
> There is no reason to believe we've hit a wall and can't invent more antibiotics in the future That just kicks the can down the road though. Assuming that the use of any antibiotic will eventually lead to a predominance of resistance, we would have to continue to invent new, effective antibiotics indefinitely. > For example, some countries crazily overprescribe antibiotics, or prescribe broad spectrum ones I don't…
Everything that reproduces is in an evolutionary arms race (https://en.wikipedia.org/wiki/Evolutionary_arms_race), so the "kicking the can" objection doesn't really make sense in this context.
There is no alternative to inventing new weapons continuously. We are simply used to winning without much effort since Fleming found penicillin, a naturally occurring fungal compound. Previous successes have limited the economics of continuing to develop new solutions, which is contributes to the uptick in resistance.
This doesn't mean we shouldn't be judicious in the tradeoffs that we choose and try to avoid a purely chemical solution to the arms race. For example, as robotics get better, we should move away from mono-cropping toward combinations of plants that naturally ward off pests. There are better ways to stay ahead than blunt tools.
Re: High time to tackle drug-resistant fungal infections
#33Earlier quoted context omitted.
> There is no reason to believe we've hit a wall and can't invent more antibiotics in the future That just kicks the can down the road though. Assuming that the use of any antibiotic will eventually lead to a predominance of resistance, we would have to continue to invent new, effective antibiotics indefinitely. > For example, some countries crazily overprescribe antibiotics, or prescribe broad spectrum ones I don't…
We don’t have to keep creating new antibiotics indefinitely. There’s always some cost to resistance. Once a drug is no longer present in an environment, non-resistant strains tend to outcompete resistant ones. That is if you just stop using an antibiotic, bacteria will tend to lose resistance to it. Theoretically once you have enough antibiotics that we can retire drugs with heavy resistance and keep cycling them, yo…
There's a lot baked into that theory (well, hypothesis) though. We haven't gone through a cycle like that yet that I'm aware of, moving back to an old antibiotic because the newer one is no longer effective.
Looking just at the evolution of it, there would need to be pressure to actively select against the learned resistance. Maybe it would be lost eventually, but we couldn't rely on that unless something pushed the bacteria away from it rather learning to resist the new antibiotic in addition to the old one.
Re: High time to tackle drug-resistant fungal infections
#34ummmm, hmmmmmmm, It's high time we realised that we are the largest single niche, and animal biomass, that possibly, has ever existed, and it is a law of biology, that each niche will be filled. This means that any peicemeal approach is going to lagg, and uncontrollable epidemics become more and more likely. Confounding factors are that our diets and lifestyles are converging into a more homegenous whole, and all in…
"By weight, human beings are insignificant."
https://www.vox.com/science-and-health/2018/5/29/17386112/al...
(Sorry you're getting down voted.)
Re: High time to tackle drug-resistant fungal infections
#35Earlier quoted context omitted.
Looks like this could affect how we grow crops, maybe pish for more different techniques to avoid pesticides, and also lead to new life habits. I hope WHO or some group of researchers somewhere will start studying how to tackle these fungi infections. Given the current situation of global conflicts, political situation, and economy around the world, if these infections become more widespread and resistent if could be…
Pesticides have nothing to do with this. Staple crops in the United States essentially do not use fungicides anymore. GM crops have negated that need. Edit: what did I say that was incorrect?
n.b. Down votes are not mine
Azoles (and other antifungals) are indeed still used in the US and there is documented azole resistance in important opportunistic fungal pathogens such as Aspergillus in the US:
• Celia-Sanchez BN, Mangum B, Gómez Londoño LF, Wang C, Shuman B, Brewer MT, Momany M. Pan-azole- and multi-fungicide-resistant Aspergillus fumigatus is widespread in the United States. Appl Environ Microbiol. 2024 Apr 17;90(4):e0178223. doi: 10.1128/aem.01782-23. Epub 2024 Apr 1. PMID: 38557086; PMCID: PMC11022549. -- https://pmc.ncbi.nlm.nih.gov/articles/PMC11022549/
Table 1 in this paper gives estimated azole use in various countries. US is lower than many European nations but still nowhere near zero.
• Burks C, Darby A, Gómez Londoño L, Momany M, Brewer MT. Azole-resistant Aspergillus fumigatus in the environment: Identifying key reservoirs and hotspots of antifungal resistance. PLoS Pathog. 2021 Jul 29;17(7):e1009711. doi: 10.1371/journal.ppat.1009711. PMID: 34324607; PMCID: PMC8321103. -- https://pmc.ncbi.nlm.nih.gov/articles/PMC8321103/
Re: High time to tackle drug-resistant fungal infections
#36#proudinvestor (very early angel) in Amplyx pharmaceuticals (fosmanogepix) from many years ago.
fosmanogepix has proven anti-fungal activity in 4 of the 5 target classes and is in stage III trials.
https://pmc.ncbi.nlm.nih.gov/articles/PMC11131969/
Re: High time to tackle drug-resistant fungal infections
#37> Between 30% and 60% of the people it infects will die.
I assume there's an implicit "within x amount of time" here?
Re: High time to tackle drug-resistant fungal infections
#38> Between 30% and 60% of the people it infects will die. I assume there's an implicit "within x amount of time" here?
In the study I'm aware of, 18 patients became infected in hospital and there was a 28% death rate within 30 days [0]
[0] https://www.journalofinfection.com/article/S0163-4453(16)301...
Re: High time to tackle drug-resistant fungal infections
#39Practically, there's no way to stop anti-microbial resistance. We've only been capable of using said drugs for an x number of years because of the relatively long time it takes for these resistant spores to become dominant in most soil around the planet. The problem isn't really the development of resistance itself but our way of farming is the perfect petri-dish for fungal and bacterial evoluton. E.G. large monocrop…
I don't think that's right. * There is limited evidence that farming use of antibiotics is what drives resistance in clinical cases. That is - we use enormous amounts of antibiotics in farming, but the resistance it creates doesn't really seem to move into the hospitals. * There is no reason to believe we've hit a wall and can't invent more antibiotics in the future. Historically we haven't focused much on antibiotic…
I agree that there is still a lot we can do to combat fungal disease.
However, your points 1, 2, and 4 unfortunately don't apply well to anti-fungals.
* "There is limited evidence that farming use of [anti-fungals] is what drives resistance in clinical cases."
Certainly not the case with respect to azoles:
-- Rhodes J, et al. Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment. Nat Microbiol. 2022 May;7(5):663-674. doi: 10.1038/s41564-022-01091-2. Epub 2022 Apr 25. Erratum in: Nat Microbiol. 2022 Nov;7(11):1944. doi: 10.1038/s41564-022-01160-6. PMID: 35469019; PMCID: PMC9064804. https://pubmed.ncbi.nlm.nih.gov/35469019/
-- Celia-Sanchez BN, Mangum B, Gómez Londoño LF, Wang C, Shuman B, Brewer MT, Momany M. Pan-azole- and multi-fungicide-resistant Aspergillus fumigatus is widespread in the United States. Appl Environ Microbiol. 2024 Apr 17;90(4):e0178223. doi: 10.1128/aem.01782-23. Epub 2024 Apr 1. PMID: 38557086; PMCID: PMC11022549.
-- Impact of the use of azole fungicides, other than as human medicines, on the development of azole‐resistant Aspergillus spp. https://www.efsa.europa.eu/en/efsajournal/pub/9200
"* There is no reason to believe we've hit a wall and can't invent more antibiotics in the future. "
-- There are very few anti-fungals, because fungi, being eukaryotes, have cell biology so close to ours. The "big three" are 1) azoles (lots of resistance; see above); 2) echinocandins; and 3) amphotericin B (highly toxic to the host)
-- One bright spot is a new antifungal published a few weeks ago in Nature, called Mandimycin: https://www.nature.com/articles/d41586-025-00801-0
* "There are still some antimicrobial treatment techniques we haven't put a lot of resources in. Like, bacteriophage treatments, or cycling antibiotics."
-- Bacteriophage don't work on fungi. Some degree of cycling and combination anti-fungal treatment are already in use.
Re: High time to tackle drug-resistant fungal infections
#40Earlier quoted context omitted.
We don’t have to keep creating new antibiotics indefinitely. There’s always some cost to resistance. Once a drug is no longer present in an environment, non-resistant strains tend to outcompete resistant ones. That is if you just stop using an antibiotic, bacteria will tend to lose resistance to it. Theoretically once you have enough antibiotics that we can retire drugs with heavy resistance and keep cycling them, yo…
There's a lot baked into that theory (well, hypothesis) though. We haven't gone through a cycle like that yet that I'm aware of, moving back to an old antibiotic because the newer one is no longer effective. Looking just at the evolution of it, there would need to be pressure to actively select against the learned resistance. Maybe it would be lost eventually, but we couldn't rely on that unless something pushed the…
This has been well researched. Most antibiotic resistance has a fitness cost. Which means the resistance is being actively selected against.
This isn’t always the case. There are some adaptations that don’t have an observable fitness cost, but the majority do. That is, in a lab when you remove the antibiotic, we observed that the number of resistant bacteria drops over time.
We have also observed this in the real world. When we reduce usage of a specific antibiotic. The percentage of resistant bacteria in the wild drops.
The question is how long you’d have to retire an antibiotic and how many different antibiotics you’d need for this strategy to be viable.