So I was wondering while studying for medicine exams...

So I was wondering while studying for medicine exams, is it possible to combine 2 molecules or antibiotics (Lets say Penicillin and Cephalosporin) and get a superantibiotic? Of curse we would have to protect the pars of molecules which are meant to connect to PBP so they would work.

Thoughts? And if you have an answer, please leave a citation or a link to proof, if you have any.

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Possibly if they have different mechanisms of actions, I don't think two antibiotics that both work on PBP would have an additional effect.

In clinical practice, sepsis is often treated with a combination of a beta-lactam and an aminoglycoside.

Also there are some cases where two molecules are mostly combined, like amoxicillin+clavulanate, piperacillin+tazobactam and imipenem+cilastatin.

Well they dont necessarily have the same function. Cephalosporins work on bacteria who have developed resistance to Penicillin, so there must be some difrence in the way the function towards PBP. Also, that was just a example. But thank you for your answer.

Penicillin resistance is mostly due to the bacteria producing beta-lactamases that break down penicillins but not cephalosporins.

The obvious exception is of course MRSA, which due to a mutation in the PBP is resistant to all beta-lactams.

That's not true, Cephalosporins are also susceptible to beta-lactamase type called cephalosporinase

Of course, I said mostly, and I also related to your example of penicillin-resistant bacteria susceptible to cephalosporins.

Ah, ok.

What would be the benefit of it?
I would prefer to use ampicilin+gentamicine at the same time than to use a super ""beta-lac-syde"".

What if the germ is resist to one of them? would both be resisted?

I think if we were to combine multiple antibiotics in one super antibiotic, then it would be pretty hard to develop resistence against it, since it would be more than lethat against bacteria, who are resistant to one of its components or even two.

what do you mean by combine?


chemically? no, and if you somehow can control the geometry of the molecule being created then its a very skeptical maybe.

if you mean just combine, then sure? done we already do that, it would just be taking multiple antibiotics at once, its litterally just that.


real life isnt ruled by video game logic

antibiotic+antibiotic doesnt equal superantibiotic, if that where possible someone would have done it by now

Yes. I mean chemically. If no, why not?

Well, i never stated that life is a video game and since Im a medicine student, I dont really have time for those.

I understand that antibiotic is a very complex molecule, but since we can combine in laboratory with enzimes molecules like Acetyl-CoA, which isnt a simple molecule by all means, then it should also be impossible to combine two non identical complex molecules like two different antibiotics or even more. Then only real challenge I see, would be that after the combination, the new molecules structure could be so awkward it would block one of the antibiotics connection point, where it connects to its target molecule. Also, the new molecule would be big, so it would have harder time moving in extra and intracelular space.

And to reply to the last point: Many things are theorized, but havent been done because we lack the technology or skills. Thats why im asking is someone knows anything about this.

no, you would be fucking up resonance, electron densities, functional group affinities, the list goes on, if you could do this it would have been done. /thread

Care to elaborate further?
I mean, they did create a synthesis version of penicillin. It is called the second generation, it was created by adding extra chains of chemicals to the side of molecule to prevent it from being stopped by B-lactamase. Sure it became toxic for humans, but it still kept its attributes of antibiotic. Can you argue versus this?

second generation of penicillin antibiotics: Meticillin, Oksacillin, Nafcillin

thats not an instance of combining two pre-existing antibiotics, it looks like in some of these instances theyre merely resistant to hydrolyzation by Penicillinase,

responding to my own post to elaborate, the issue with just putting antibiotics together is due to the specificity of how they work, when you push things around, you tend to lose functionality,

drugs work because they "fit" into certain proteins and receptors. If you glue two together you get a ball of shit that doesn't "fit" in either of the places the two original drugs operate on. Even if they split after being metabolized, you just get the effects of the two original drugs.

This. Shape determines function. Fuck up the shape, fuck up the function.

The most common practice is to combine two antibiotics that work in different pathways like lactams and aminoglycosides or two antibiotics that inhibit two separate steps in the same vital pathway. So long as you do this AND FINISH YOUR COUSE REGARDLESS IF YOU FEEL BETTER, it severely hinders the likelihood of another infection.

I used all caps because that is the main reason why resistance rears its ugly head in the first place.

These
Importance of geometry is learned rather early OP what the hell?

Again, there is the second generation of penicilin where humans added aditional chemical bonds to antibiotic molecule and it still was functioning. So geometry was intact, that proves that it is possible to combine molecules, keep the geometry intact and save the function.

already answered to the ''fitting'' part in this I have no understanding why you all assume that in 100% cases the geometry of molecule would be to awkward and the connection points would be blocked. There is a possibility to establish a connection with another molecule in distal end of another, if the connection point would be in the proximal end ( on the other side) then there wouldn't be as big problem.

Hold on guy,

"the only real challenge I see is that they can no longer bind to target sites and cannot move around the body for shit"

I.e. they don't fucking work and you already know it. Also how many medical students are there that cannot spell enzyme correctly? Different antibiotics are used for different reasons. THEIR BONUSES DO NOT STACK GG NO RE

A medical student who isnt learning medicine in English speaking country?

I never said that they cannot bind to target sites, that is one of the possibilities if the connection to another molecule results in obstruction of binding site.

About your second point: Name a reason why their attributes wouldn't stack? If we would make a successful connection between the molecules without the obstruction of binding centers.

Antibiotic mechanisms are usually way to different. Could you use a tetracycline with a quinone? Something that disrupts tRNA function with something that disrupts transcription to mRNA? Not with one molecule...

And if you are combining two of the same class antibiotics, why would you if one does the trick?

There's no such thing a medicine in non english speaking countries.

Well, since there are different generations of antibiotic ( penicillin isnt just one antibiotic, its just a overall name. There is Benzilpenicilin, penicillin G etc. and they have different functions, or at least just barely overlapping).

And what do you mean by ''There's no such thing a medicine in non english speaking countries.''? Is there no medicine in France? Germany, Belgium, China etc. None of them have english as a national language but they all have modern medicine.

Because antibiotic shit costs money, why bother causing shit to develop resistance when you could just give a broad spectrum and do a bact culture to find out which one it's sensitive to?

amoxicillin and clavulanic acid is given, for example, but it also has some hepatotoxic effects and you're only worsening polypharmacy.

And shit like Gent causes renal impairment and ototoxicity.

I red that in Ricks voice, thank you for that.

I understand that practicality would go to shit if such thing was to be created, but still doesnt really answer the question ''Is it even possible?''

All of the above answers have been mainly straw-mans ''Oh, it would screw up the geometry!!11!!!!'' ( I do know that I just did a straw-man myself). Completely ignoring the fact that it isnt 100% true. It might even be 99% true, but that means that there might be a method or a combination where such thing is possible.

however these are tweaks. add a chlorine here, fiddle around about with the molecule. bit like legal highs, oh yeah, lets change the prescription only amphet with one flurine and hey we have a new drug. There has been no real new diffierent anti-biotic since the 40's. Just tweaks.

So if we can make small tweaks, shoudnt it be also possible to make big tweaks with better technology?

the small tweaks all work the same way. When the bacteria cell goes to divide, the presence of penicillin makes it loose its cell wall. This kills the bacteria. All the tweaks of penicillin simply make it cope better, slightly, with different bacteria types. They all work in the same way. Attacking the bacteria cell wall when it is vulnerable.


If you want to do something great for humanity, or win a Nobel prize or something, work out a different mechanism for attacking bacteria (without of course destroying human cells as well, which the earlier tetra-cycline based anti-biotics did).

It would if you had an unlimited budget, but med charts especially for older patients can go on for pages. If you combine all those antibiotics there's a greatly increased chance that:
- Someone will prescribe an antibiotic and forget to remove it
Antibiotics have effects like I've said. Every antibiotic has side effects:
Penicillins - high sodium content (unsuitable for hypertensive patients)
Cephalosporins - hypersensitivity reactions with cross reactivity with penicillin
glycopeptides - ototoxicity, nephrotoxicity → cannot be used in patients with kidney failure and can cause people to lose their hearing
tetracyclines - cannot be used in females due to the chance of birth defects, causes gut disturbance and vitamin b deficiency
amingolycosides - also otoxic, nephrotoxic - cannot be used in patients with kidney failure
macrolides → GIT disturbance
and so on
How many people do you think fit into the category of being able to take all of them?

New classes of antibiotics have not been discovered for a very long time and we are running out of them. That's why people don't use antibiotics if at all possible. Also people may be anaphylactic to or develop anaphylaxis to drugs which is really not ideal.

Also cost is an absolute huge factor, especially if you are Murrican from what I hear. And people stop taking medications all the time if the dosing is complicated. If you combined all of these drugs you would have to figure out all the pharmokinetics of all of them (drugs all have different volumes of distribution and ways of being metabolised, for example) which is a huge pain in the ass. Not feasible in my opinion. There's a greater likelihood that when antibiotics fuck off for good people will need to resort to distilling antibodies by innoculating animals and purifying the products, but it's really slow.

(cont)
Multiple drugs targetting different pathways at once does happen in the case of antiretrovirals and shit for HIV because it mutates fast and you don't know which way it will turn and it's basically impossible to eradicate.

With a serious bacterial infection you're just going to basically culture the bacteria causing the issue and test it up against every single drug and find out which antibiotic is most effective. So you won't need to use the shit/non effective ones or effective ones that can cause issues with the kidneys etc.

what research is going on for ewer methods of attacking bacteria? The penicillin variants just interfere with the reproduction process/cell wall formation. Are there any other ways bacteria can be inhibited that are new?

But they didn't combine two different antibiotics together to create a superantibiotic. They just added different functional groups to alter the properties of the molecule. How dense are you?

Almost all the new antibiotics are just modifications/new gens of original antibiotics. There haven't been any actually new ones in years.

who.int/mediacentre/news/releases/2017/running-out-antibiotics/en/

It's expensive, they can't be toxic and standards are getting higher all the time for the amount of human risk that can result and pharm companies would rather invest money in drugs that will need to be taken multiple times for the rest of a patients life than a solution like antibiotics that will stop being used within a very short time.

Worst comes to worst we're probably just going to use antibody therapy. It's just slow as fuck to produce.

>tfw most antibiotics have a MIC/clinical usage conc. that's also the exact sweet spot for developing resistance

>tfw people with cystic fibrosis and MRSA are given ABs at conc. promoting biofilm formation, effectively killing them in the long run

>medicine, the holy grail of science

I don't know how to explain why it won't work other than saying that your intuition of biological chemistry and metabolism is somewhere between flawed and flat-out wrong. Even if you attached the two units by a long, thin string, so that almost no blockage occurs around one specific part of the molecule (presumably derived from a functional antibiotic), this COMPLETELY changes everything about the drug's solubility in and permeability through membranes and extracellular / intracellular spaces. Having a drug "fit" in the right spot is probably around 10% of the battle in drug discovery. Maybe 50% in only the most extreme cases. There are many different variables that have to be simultaneously tuned to produce efficacious, and more importantly SAFE, drugs. Cyanide is a fantastic antibiotic, but it'll kill the host when prescribed in "therapeutic" doses. Likewise there have been probably thousands of compounds shown to have amazingly powerful potential as drugs for all kinds of problems in trials with bare cells in a lab, but they never make it to being effective "drugs" because they are metabolized before they can do anything or never get where they need to go in the first place.

>completely ignoring the fact that I already stated that I understand that the new drug wont be able to maneuver in extracellular space.

How about bacteriophages? Do you see them becoming a huge method of treatment in future? Also what bout ''infecting'' bacteria with plasmids who have information in them for a substance which is toxic or harmful for the bacteria. In theory, couldnt we be able to ''infect'' a bacteria with it, and then the bacteria would produce its own poison.