Dual action antibiotic could make bacterial resistance nearly impossible
phys.org
phys.org
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.]
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
That's quite an interesting molecule :)
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.
Enterohepatic Recirculation is heavily influenced by diet which is why fiber and specifically leafy greens seem to be helpful for liver heath. https://en.wikipedia.org/wiki/Enterohepatic_circulation
This is also one of the reasons activated charcoal is useful after ingesting a wide range of harmful substances.
I don't see the connection to what you wrote before it; would you mind to explain?
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.
"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."
What are the advantage/drawbacks of the article method over Bactrim method ?
My understanding is that in this case bacteria would have to develop resistance to two mechanisms at the same time, which is much more difficult.
Mandatory quote: "Life, uh, finds a way"
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.
> 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)?
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.
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
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.
From the article, it does look like they're smushing two antibiotic active sites into one molecule, so it seems a somewhat similar idea
In the normal dual antibacterial cases just developing a single resistance and acquiring the right plasmid is enough.
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.
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.
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.
At least today robots are not ready for general hospital needs. time will tell if the future works out.
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.
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.
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 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)
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!
Bacteria: Hold my beer.
do you know how many bacteria, all mutating and swapping genes, there are out there?
also, dual therapy, particularly for TB has been used for years, but TB is still with us.
My interrogation hold : aren’t bacteria infections quantity (and therefore duplication and mutation) influenced by the growing number of host?
1/4 people carry TB in the world. Most asymptomatic.
TB been with humans as long as humans have been around, and it will be with humans as long as we're here.
Multidrug Resistent TB is a thing though.