[_heimdall]

> 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 think its as simple as over prescription being the problem. My grandmother is pretty I'll these days, she suffers from dementia, is sick frequently, and generally just very warn down. She had a respiratory infection this week and while at the doctor they also found that she has a UTI. The prescribed her two different, non-broad spectrum antibiotics.

I don't think anyone would consider that over prescribing, and she likely would have a very bad outcome without it, but it also seems totally reasonable that her scenario could still lead to antibiotic resistance. Her immune system just doesn't work well anymore, the antibiotics will take out most of the infection and her symptoms will likely go away but I wouldn't expect her body to do the job of cleaning up the rest of the infection, leaving the more resistant strains around in her system.

[sarchertech]

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, you won’t need to keep creating new antibiotics.

[_heimdall]

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.

[sarchertech]

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.

[_heimdall]

Sure, but I think we agree then. What you describe is a hypothesis based on a few important assumptions. For example, that controlled lab studies are predictive analogs for the natural world, that a drop in resistance in such a controlled study will match a real world scenario, and that the rate at which resistance is lost can reasonably be matched by cycling in different drugs.

I'm not saying it isn't possible, maybe it is! Only that its a hypothesis and that the key assumptions are still just that rather than known parameters.

[sarchertech]

We have more than lab studies, we have real world observations that show the percentage of resistant strains dropping when we reduce the use of a specific antibiotic.

We may not be able to produce new antibiotics fast enough to get to the point where we have enough to cycle them effectively. That’s entirely possible.

But we have very good evidence that there is a point at which we would have enough. I mean at the limit there is a maximum amount of information bacteria can store in their genes, so there certainly exists some maximum number of resistances they can retain.

My point isn’t that we’re going to have enough to do this in x years. My point is that while we don’t know how many different antibiotics we need, we are almost certain that that number isn’t infinite.

[biomcgary]

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.