It’s unclear why the same benefit couldn’t be achieved by mixing two traditional antibiotics with different mechanisms of action. Maybe the combined dosage would stress the liver too much?
Last year I was hospitalized and quarantined for Tuberculosis, which is fairly strong against antibiotics so the antibiotic therapy is 6 months long (minimum), and that's precisely how I was treated, by combining first 4 then 2 antibiotics in order to prevent the bacteria from developing resistance, but you're right, it's super bad for your liver, I've seen heavy alcoholic patients in the same ward that were refused treatment because "we would destroy your barely functioning liver and kill you", and watched them just die, but I don't think it completely prevents the bacteria from building resistance, it just minimizes the odds to a significant degree.
But Wikipedia has a long article on Hepatotoxicity[0] and that suggests discontinuation of the drugs involved can allow the liver to heal (if discontinued early enough).
As a patient, you need to be conscious to ask questions and retain at least some control over your treatment whenever you can. If you're overwhelmed by what you are being told or concerned about the planned course of treatment, always ask questions, especially about long term implications and risks and how those are addressed. Generally doctors like being asked about medical things and are willing to answer when they are able. [Individual experiences may vary etc.]
I was prescribed a drug that's sold under brand name Heparegen over here that I had to take for months, apparently the active compound is called Timonacic: https://drugs.ncats.io/drug/E5913T3IBL
We also had to take these pills twice a day throughout my hospital stay under the supervision of nurses who would ensure we actually take all of our medication.
Also, a few months later of taking this drug, my liver is perfectly healthy (results from around two weeks ago): https://i.imgur.com/WMpH4t9.png
This is in general good advice, but in the context of healing the liver plants are generally the type of poison your liver exists to filter in the first place, so a meat heavy diet is likely better. Of course you are trading longer term cardiovascular health for short term liver healing so don't do this for long, but if your liver is very damaged avoid plants as well for a short term.
The primary method of action for activated charcoal is to bind to a substance in the digestive system and prevent its absorption into the body.
Unfortunately there can be a significant delay between ingesting the toxin and activated charcoal. However, substances can pass in both directions. So by lowering the concentration in the intestine it also increases the amount that diffuses back into the intestines after having entered the bloodstream.
Aside from the other comment on fiber (which can always be supplemented without fresh greens if concern is phytotoxins)... Given the evidence for impact of neu5gc on liver, maybe watch out what types of meat you are consuming too, and avoid mammals.
You need to get very significant amount of liver damage to the point scar formation already occured. Without constant damage and scarring liver tissue heals over time.
Trimethoprim/sulfamethoxazole is a widely used such combination antibiotic.
"Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections."
Hitting the population with multiple mechanisms simultaneously masks the selective advantage of slightly better phenotypes against the individual attacks.
There's a spread in individual characteristics, and if the attacks are applied independently, the more vulnerable individuals perish more readily and the genetic distribution goes on to trying states mainly near the more resilient ones against that attack.
But faring a bit better against Attack-1 is practically no better than not, if Attack-2 is always going to wipe out all Attack-1-resistance phenotypes about equally anyway.
Executed just right it attacks the conditions for gradual evolution by breaking most of the corrective signal.
Isn't it exactly the same situation? In one case you have two substances that attack cells by two different mechanisms, and in the other you have a single substance that attacks cells by two different mechanisms. In either case a strain that doesn't have resistance to both mechanisms will get wiped out, since just one of them destroys the cells or prevents them from reproducing. Even if some sub-strains develop resistance to one of the mechanisms, it won't matter because they will get wiped out by the other.
But if doctors don’t always prescribe these two antibiotics to be used in tandem, then microbes will have an opportunity to evolve resistance to each one in isolation, putting those resistant genes out in the world. Whereas in this case, any bacteria ever encountering this drug will be hit by both mechanisms at once.
... but the article describes that the antibiotics being discussed combine structures from classes of antibiotics which are already used independently.
> Macrolones are synthetic antibiotics that combine the structures of two widely used antibiotics with different mechanisms. Macrolides, such as erythromycin, block the ribosome, the protein manufacturing factories of the cell. Fluoroquinolones, such as ciprofloxacin, target a bacteria-specific enzyme called DNA gyrase.
So if macrolides and fluoroquinolones are each used independently already, and strains resistant to each of them independently, and these strains have an opportunity to co-occur and do horizontal transfer, wouldn't we expect that to have resistance to a single drug that combines both mechanisms? I guess, when a strain develops resistance, is it to the mechanism overall (e.g. a more robust ribosome or differently shaped DNA gyrase enzyme) or is the resistance somehow specific to a specific molecule (e.g. some enzyme that finds and breaks-down the drug based on other aspects of its structure)?
Good observations.
There are many possible mechanisms for resistance, and with this involving bacteria I expect pretty much all are sooner or later used.
Some ways are more specific to the substance, such as changing the target to fit worse or be less sensitive to the effect. Some can be quite general, such as actively pumping the molecules out of the cell.
In these cases there won't probably won't be that much wiggle room for altering the targets. Ribosomes and DNA-associated enzymes tend to be very very busy doing critical work against a lot of substrates and products, and are already heavily optimized for their normal tasks. I'd say it's no coincidence these mechanisms were chosen for a novel antibiotic attempting to mitigate resistance development.
Degrading the antibiotic, throwing it out, etc are still viable options, but it's still very nice to see someone finally trying to do this more right, even if basing it on elements of existing classes adds some risk that there are strong initialization states for resistance development out there.
Good question. Take many many antibacterial molecules to kill a bacteria, so there are two plausible methods. The first is that two compounds can have different pharmacokinetics. That is to say, they move through the body in different ways and have different concentration profiles.
The second is about how they are used. Two separate compounds with the same pharmacokinetics could be effective if you use them in parallel, but you have to contend with the fact that real human users may not always use them that way. If two different companies make compound a and compound B, it is virtually impossible to prevent someone somewhere from using them separately
I meant that if you have two separate substances, we can reasonably assume they will also be used individually, giving bacteria chance to develop resistance. Then strains with different resistances meet in one organism and swap genes.
Although that's extremely simplified. I recall reading that the usual mechanism is somewhat different. When you take one antibiotic to fight one pathogen, also attacks other bacteria in your gut microbiome (also those benign and even useful). Those bacterial also develop resistance. Unfortunately they can later share their resistance genes with harmful bacteria.
I'm not a biologist, but I'm guessing that having the concentrations of two antibiotics peak at the same time etc is much much trickier than having one molecule with two mechanisms of effect. Thus in actual (not perfect) use you end up with both effects active within a bacterium at one time, rather than potentially having some distance between the peaks.
From the article, it does look like they're smushing two antibiotic active sites into one molecule, so it seems a somewhat similar idea
The antibacterial resistance is often on small DNA loops called plasmids which are often and easily exchanged between bacterial species. I assume this has to do with that, either the resistance would have to develop twice in the main genome or twice on the same plasmid.
In the normal dual antibacterial cases just developing a single resistance and acquiring the right plasmid is enough.
It's a probability game isn't it. There's a chance of that super super bug given normal antibiotics. But also chances are that any super super bug is going to have a downside that stops it spreading unhindered through other hosts or something like that.
There's always the possibility of a microbe/prion/other that can attack and consume all DNA based life forms. Or a 'nearby' gamma ray burst that sterilises everything within 200 light years.
I’ve heard for years that antibiotic resistant bacteria don’t really seem to be a threat because they tend not be very successful in the wild. Like it’s going to be, at best, a very localized outbreak because competitive pressures don’t reward the trade offs. That’s still true?
Hospitals are an environment where they have the advantage and where humans who are most vulnerable are. Outside of a hospital they don't do as well, but the local environments they do well in are still important even if they are a minority.
Also, if the bacteria targets humans or things humans treat (cats...) anything not resistant will not survive as well because when we detect sickness we treat it and select for anything resistant.
Research indicates that using copper or copper alloys in hospitals reduces nosocomial infections [0], but people seem to prefer stainless steel because it looks cleaner.
Your summary is stronger than the conclusion of that paper. They also didn't compare stainless steel to copper, they only established copper should work. Here is a random paper I found (first when searching), https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123372/ which gives the lifespan of MRSA on copper at 6 hours, and on stainless steel at 72 hours - the important take away here is the lifespan on both is far too long so rely on surfaces and so we must disinfect surfaces not relying on their ability to kill bacteria. We also need to get health care professionals to wash their hands more - the article quotes some seriously awful handwashing rates.
Note that the above paper only quotes lifespans for a couple microbes. We care about all microbes, if even one harmful microb of any type survives we have an infection vector anyway.
Unfortunately that doesn't work either as a large concentration of experts in one place is a useful feature of large hospitals. If something goes wrong you want the right expert available to help. An expert who is currently doing surgery on someone else isn't available to jump in on your problem. When things go per routine you only need the small team, but having a larger team for if things go wrong is helpful.
At least today robots are not ready for general hospital needs. time will tell if the future works out.
Maybe expertise should be more widespread and communication less reliant on physical proximity?
Although I agree that I'm some scenarios teaming up is unavoidable.
But there's a spectrum between private doctors and clinic of a billionaire and huge warehouse you put sick or wounded people in mostly so they have a place to die.
Do you know how long it takes to become a brain Surgeon? How about a Heart surgeon? Now imagine someone was both - how much more time would that take? Now if that person existed, would you want them operating on your - knowing that they have less real world experience?
Specialization is a good thing. In a complex field like medicine it is a must. There is too much for anyone one person to be an expert in it all, and experience is very valuable so again we want someone to specialize and get a lot of experience in a narrow field.
He caught it in the hospital after a routine surgery. His condition deteriorated dramatically, was in a comma for a couple of days but thankfully survived.
After he recovered they could still detect the bacteria dormant in the liver for three years, at which point he re entered the hospital to start a heavier multi-antibiotic treatment plan that could potentially evict the bacteria but could also cost his liver.
He won after all, but his health condition overall never returned to the original.
Making extra genetic material and their resistance products can be a liability if they're useless (and so would slowly be lost), but there's all sorts of chemical combat between microbes in lots of environments and you can't be sure the resistance adaptations aren't good for other things too, potentially something different.
Don't know much about microbiology, but saw this ( https://www.youtube.com/watch?v=VPSm9gJkPxU ) video about biological "motors" which allow for movement in the organisms (chemotaxis). In the end, they speculate that future antibiotics could target a bacteria's motors to disrupt its movement.
Not sure how difficult will it be for the bacteria to gain resistance to this approach.
What's the issue? He has faith in something. But he's discussing the science without any religious stuff. Even then he never said anything along the lines that would compare the mechanism with creation of god or something. What's with all the hate?
Well, aside from the generic defense mechanism of pumping unwanted chemicals out of the bacterial cell, or an enzyme for degrading the antibiotic.
Multiple mutations could also occur if the cells are being exposed to sublethal amounts of the antibiotic, say in sewers (which would also be an environment for evolution of enzymes to degrade the chemical.)
Step 1: We are overconfident that bacteria won't become resistant to this formula
Step 2: Formula sold to developing countries pharmaceutical industry
Step 3: Antibiotic given to every man, woman, and child with even the most trivial of symptoms
Step 4: Widespread bacterial resistance to dual action antibiotic.
Step 5: rinse, repeat
We need better antibiotic distribution practices before we unleash more formulas on the world. Anything this strong should never be given to farm animals and should not be given to any developing country not willing to implement strong access control on a patient by patient basis (ie verified infection with bacteria that can be controlled with the formula and verified completion of course)
Step 3: even worse, to every pig and cow, to make them grow faster in worse conditions.
I think the main problem is in lack of awareness. People don't understand that antibiotics have downsides. But how to spread awareness without swinging the pendulum too far and creating an ugly stepsister of the anti-vax movement? It certainly seems that humanity doesn't have much capacity for nuanced thought when it comes to "chemicals".
My argument stems from stories from India of newborns getting multidrug resistant bacteria shortly after birth, presumably from the hospital they were born in because standard medical practice in India is to be given antibiotics for even a minor cough (I have been there long enough and witnessed this firsthand). It’d be really cool if pharmacies there would put up more barriers to distributing these!
Please don't take HN threads on generic flamewar tangents. I'm sure that wasn't your intent, but we got a religious flamewar out of this. Those get predictably worse as they go along, so it's important not to seed them.
Yes. He mentioned the controversy and the arguments (and his biases) but refrains from preaching or privileging one side over the other, instead electing to express joy and wonder.
I was pretty impressed with his approach, so I'll link the relevant section below (last ~3m). I'd argue abstaining from viewing (and commenting as much) is evangelizing more than Destin here.
It is fairly difficult to be perfectly objective about everything we discuss. We all bring our own bias and experiences to just about everything we do and say.
In Dustin’s case, he is being open about his background and perspective. Isn’t that more commendable than trying to feign objectivity?
Clearly you can agree or disagree but being annoyed at his transparency seems to neglect consideration for the alternative.
TL;DR irreducible complexity is a cop out that says "We don't understand this therefore it is unexplainable" and it is obviously absurd when applied to literally any field other than biology.
But drug resistance is already really hard to develop. As you say, there are an almost unfathomable number of -- let's say staph -- bacteria running around, infecting millions of people per year, and still it's taken most of a century to develop MRSA. 100 million times might make MRSA v2 take millennia to arrive.
Actually, the rate of population increase peaked in the 1960s. The growth once seen as exponential is beginning to look like an s-curve, if you pay attention to the derivative.
