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I’m a bit confused why antibiotic resistant bacteria is so scary. My layman understanding is that antibiotics gum up the mechanism to produce the cell wall. S

I’m a bit confused why antibiotic resistant bacteria is so scary. My layman understanding is that antibiotics gum up the mechanism to produce the cell wall. Sure, bacteria may develop where the mechanism works a bit differently and is not affected by a certain chemical. But it seems like “disrupt cell wall production” is a huge target and we could probably disrupt it in many other ways. Humans lack a cell wall entirely, so we “just” need to avoid side effects in some other system. Is the concern that studies to confirm lack of effects will take too long? Not that it’s a difficult engineering challenge? Couldn’t we be doing this research already, of finding other ways to disrupt the mechanism?

make3 4y ago
the products that both attacks the bacterias & are perfectly safe are probably very very hard to find, right. the product needs to be safe to flood your whole system with, because that's how pills work, you eat it and it diffuses everywhere in your system, there is zero targeting. Plus ideally it should kill all the bacterias very fast so none can develop resistance. it seems like it would be an incredibly hard balance.
John23832 4y ago
> I’m a bit confused why antibiotic resistant bacteria is so scary. It's scary because if you can't kill the bacteria, the bacteria kills you. -- > My layman understanding is that antibiotics gum up the mechanism to produce the cell wall. This layman's idea is incorrect. Not all antibiotics work on cell walls. Not all bacteria have defined cell walls. Look up Mycoplasma. -- > Is the concern that studies to confirm lack of effects will take too long? Not that it’s a difficult engineering challenge? Couldn’t we be doing this research already, of finding other ways to disrupt the mechanism? Most of the antibiotics we have were either found by accident, or computed derivatives of something that was found by accident. We've exhausted the low hanging fruit. More complex antibiotics often have bad side effects (ciprofloxacin) or are effective enough that we use them in the most guarded fashion to keep them in the chamber when needed (carbapenem derivations). -- There's a metric crap ton of money going into the research of new antibiotics, it's just not straight forward.
- shagie 4y ago
  > There's a metric crap ton of money going into the research of new antibiotics It's getting more attention, but its been faltering for a long time. https://news.bloomberglaw.com/health-law-and-business/antibiotic-research-lacks-funds-in-fight-against-resistant-germs https://news.bloomberglaw.com/health-law-and-business/antibi... > Venture capitalists are investing far less funds to develop new antibiotics than they are for oncology drugs, according to a new report that highlights the need for more financial incentives to fight off the growing threat of drug-resistant bacteria. > The report, published Monday by the Biotechnology Innovation Organization, found that investors are increasingly shying away from antibiotic research due in part to large companies exiting the space. That’s left small companies, that typically rely on investment capital, struggling to carry out new clinical trials. > Newer antibiotics are more important than ever as the Covid-19 pandemic has forced people into hospitals for longer periods of time, increasing the chances for the spread of antibiotic-resistant germs, the biotech trade group said. > But in the past 10 years, venture capital funding for U.S. antibiotic development amounted to $1.6 billion, compared to $26.5 billion for oncology, according to Monday’s report. The group noted that there are currently 64 new antibacterial therapeutics in the clinical trial pipeline, 80% of which originated from small companies. The report mentioned is The State of Innovation in Antibacterial Therapeutics - https://www.bio.org/sites/default/files/2022-04/BIO-Antibacterial-Report-2022.pdf https://www.bio.org/sites/default/files/2022-04/BIO-Antibact...
toast0 4y ago
> I’m a bit confused why antibiotic resistant bacteria is so scary. Because it can makes otherwise simple to treat bacterial infections into an ICU stay. ICUs don't have a lot of spare capacity, and it's difficult to add more.
Calavar 4y ago
This is a very good question. The practical issues with antibiotic resistance may not be that obvious to a layperson because they tend to pop up in the hospital setting as opposed to the clinic setting that most people are familiar with. The antibiotic bottleneck centers around patients who show up to the hospital with very vague signs of infection (fever, sweats, rigors, lethargy, etc.) and are sick. Like on the verge of going to the ICU sick. Or already in the ICU sick. These people need an effective antibiotic and they need one fast. You don't have the luxury of sending a culture to the lab and waiting for the antibiotic susceptibility profile to come back because that can take multiple days. So you need a toolbelt of "broad spectrum" antibiotics that are highly effective against the dozen or so bacteria that are the most common culprits of serious infection - something that you can use in the critical first 48 hours, while you're still waiting for culture results. In practice (at least in the US), your selection of broad spectrum antibiotics is limited to vancomycin plus either cefepime or combination piperacillin/tazobactam. That's it. There really aren't very many other antibiotics that are effective against a sufficiently wide range of bacteria. We do have "back up" antibiotics to use if those fail, but these are powerful agents that come with some really nasty side effects, like seizures (for carbapenems) or widespread muscle breakdown (for daptomycin). And they are pretty limited in number too. If vancomycin, cefepime, or piperacillin/tazobactam resistance starts to become a lot more common before the next generation of antibiotics comes in, we're screwed. And antibiotic development has been stuck in a rut for decades.
- pfannkuchen 4y ago
  Oh that's very interesting. So the problem isn't just finding a way to gum up the /single/ cell wall production process that is common across all bacteria species-- it's doing it in a way that targets some commonality between the many such mechanisms that differ per species, across all relevant species. And I suppose that between species this difference can be non trivial. Literally 4D chess and we don't even know what the board looks like (okay it isn't chess but it is 4D).
  - Calavar 4y ago
    Yes, exactly. For example, Gram positive and Gram negative bacteria have very different structures to their cell walls, and penicillins tend to be effective for Gram positive bacteria, but not Gram negative bacteria. There can be other considerations too. Rickettsial species, as an example, live inside their host cells, so you need an antibiotic that can penetrate into a human cell, which most antibiotics can't. Basically, there's plenty of antibiotics that are effective against, say, 25% of the critical bacterial species, but very few that cover 90%+. So emerging resistance to any one of those few would be a very, very big problem.

make3 4y ago

the products that both attacks the bacterias & are perfectly safe are probably very very hard to find, right. the product needs to be safe to flood your whole system with, because that's how pills work, you eat it and it diffuses everywhere in your system, there is zero targeting. Plus ideally it should kill all the bacterias very fast so none can develop resistance. it seems like it would be an incredibly hard balance.

John23832 4y ago

> I’m a bit confused why antibiotic resistant bacteria is so scary. It's scary because if you can't kill the bacteria, the bacteria kills you. -- > My layman understanding is that antibiotics gum up the mechanism to produce the cell wall. This layman's idea is incorrect. Not all antibiotics work on cell walls. Not all bacteria have defined cell walls. Look up Mycoplasma. -- > Is the concern that studies to confirm lack of effects will take too long? Not that it’s a difficult engineering challenge? Couldn’t we be doing this research already, of finding other ways to disrupt the mechanism? Most of the antibiotics we have were either found by accident, or computed derivatives of something that was found by accident. We've exhausted the low hanging fruit. More complex antibiotics often have bad side effects (ciprofloxacin) or are effective enough that we use them in the most guarded fashion to keep them in the chamber when needed (carbapenem derivations). -- There's a metric crap ton of money going into the research of new antibiotics, it's just not straight forward.

shagie 4y ago
> There's a metric crap ton of money going into the research of new antibiotics It's getting more attention, but its been faltering for a long time. https://news.bloomberglaw.com/health-law-and-business/antibiotic-research-lacks-funds-in-fight-against-resistant-germs https://news.bloomberglaw.com/health-law-and-business/antibi... > Venture capitalists are investing far less funds to develop new antibiotics than they are for oncology drugs, according to a new report that highlights the need for more financial incentives to fight off the growing threat of drug-resistant bacteria. > The report, published Monday by the Biotechnology Innovation Organization, found that investors are increasingly shying away from antibiotic research due in part to large companies exiting the space. That’s left small companies, that typically rely on investment capital, struggling to carry out new clinical trials. > Newer antibiotics are more important than ever as the Covid-19 pandemic has forced people into hospitals for longer periods of time, increasing the chances for the spread of antibiotic-resistant germs, the biotech trade group said. > But in the past 10 years, venture capital funding for U.S. antibiotic development amounted to $1.6 billion, compared to $26.5 billion for oncology, according to Monday’s report. The group noted that there are currently 64 new antibacterial therapeutics in the clinical trial pipeline, 80% of which originated from small companies. The report mentioned is The State of Innovation in Antibacterial Therapeutics - https://www.bio.org/sites/default/files/2022-04/BIO-Antibacterial-Report-2022.pdf https://www.bio.org/sites/default/files/2022-04/BIO-Antibact...

toast0 4y ago

> I’m a bit confused why antibiotic resistant bacteria is so scary. Because it can makes otherwise simple to treat bacterial infections into an ICU stay. ICUs don't have a lot of spare capacity, and it's difficult to add more.

Calavar 4y ago

This is a very good question. The practical issues with antibiotic resistance may not be that obvious to a layperson because they tend to pop up in the hospital setting as opposed to the clinic setting that most people are familiar with. The antibiotic bottleneck centers around patients who show up to the hospital with very vague signs of infection (fever, sweats, rigors, lethargy, etc.) and are sick. Like on the verge of going to the ICU sick. Or already in the ICU sick. These people need an effective antibiotic and they need one fast. You don't have the luxury of sending a culture to the lab and waiting for the antibiotic susceptibility profile to come back because that can take multiple days. So you need a toolbelt of "broad spectrum" antibiotics that are highly effective against the dozen or so bacteria that are the most common culprits of serious infection - something that you can use in the critical first 48 hours, while you're still waiting for culture results. In practice (at least in the US), your selection of broad spectrum antibiotics is limited to vancomycin plus either cefepime or combination piperacillin/tazobactam. That's it. There really aren't very many other antibiotics that are effective against a sufficiently wide range of bacteria. We do have "back up" antibiotics to use if those fail, but these are powerful agents that come with some really nasty side effects, like seizures (for carbapenems) or widespread muscle breakdown (for daptomycin). And they are pretty limited in number too. If vancomycin, cefepime, or piperacillin/tazobactam resistance starts to become a lot more common before the next generation of antibiotics comes in, we're screwed. And antibiotic development has been stuck in a rut for decades.

pfannkuchen 4y ago
Oh that's very interesting. So the problem isn't just finding a way to gum up the /single/ cell wall production process that is common across all bacteria species-- it's doing it in a way that targets some commonality between the many such mechanisms that differ per species, across all relevant species. And I suppose that between species this difference can be non trivial. Literally 4D chess and we don't even know what the board looks like (okay it isn't chess but it is 4D).
- Calavar 4y ago
  Yes, exactly. For example, Gram positive and Gram negative bacteria have very different structures to their cell walls, and penicillins tend to be effective for Gram positive bacteria, but not Gram negative bacteria. There can be other considerations too. Rickettsial species, as an example, live inside their host cells, so you need an antibiotic that can penetrate into a human cell, which most antibiotics can't. Basically, there's plenty of antibiotics that are effective against, say, 25% of the critical bacterial species, but very few that cover 90%+. So emerging resistance to any one of those few would be a very, very big problem.