Evolution works on fractions. Bacteria develop resistance because there's always a tiny fraction that survive the onslaught of whatever drug used, that tiny fraction survives and the remaining population is now completely resistant.
This is normally not a problem because the drug kills enough of them that your immune system mops up the rest.
The problem now is that the fraction has slowly become larger and larger until the point that a viable population of survivors remains to pass on their genes.
The way around this is to use multiple drugs that require multiple different mutations to survive. If before each drug left a tiny fraction of population, the intersection of those drugs will leave a fraction of a fraction of a fraction. Not enough to make a viable population that passes along multiple resistances.
In some cases, you can stack drugs in a way that requires bacteria to have three mutually exclusive mutations, so they're dead either way. There is an antibiotic candidate right now that is estimated to be 15,000x more effective because of smart design to require 3 different mutations to survive, but those mutations don't work together.
>The way around this is to use multiple drugs that require multiple different mutations to survive.
Or it might just as well end up beeing the fastest way for creating, even more, MRSA bacteria strains because the harsher the treatment, the more sturdy the survivors we will be.
>There is an antibiotic candidate right now that is estimated to be 15,000x more effective because of smart design to require 3 different mutations to survive, but those mutations don't work together.
As corny as it might sound, we really shouldn't underestimate nature like that, it's part of the reason what got us in this mess in the first place. If we can design something requiring 3 different mutations to survive, then sooner or later nature is gonna evolve something with those 3 different mutations. Nature has played this game far longer, and far more successful than we will ever be able to.
That's why imho we need a better approach than "use more types of antibiotics", as that's essentially exactly what we've been doing this whole time.
HIV is a far more formable resistance target than bacteria (in the short term at least). We know what we need to do - develop new antibiotics and stop giving them one at a time. Like the famous quote from Churchill about Americans we will eventually get there after we exhaust all the alternatives.
Edit. When I was a science undergraduate in the early 1990s on my own I came up with HAART (not original of course) from first principles. It seems so obvious that I didn't understand why it was not standard practice (such is the arrogance of youth).
This is normally not a problem because the drug kills enough of them that your immune system mops up the rest.
The problem now is that the fraction has slowly become larger and larger until the point that a viable population of survivors remains to pass on their genes.
The way around this is to use multiple drugs that require multiple different mutations to survive. If before each drug left a tiny fraction of population, the intersection of those drugs will leave a fraction of a fraction of a fraction. Not enough to make a viable population that passes along multiple resistances.
In some cases, you can stack drugs in a way that requires bacteria to have three mutually exclusive mutations, so they're dead either way. There is an antibiotic candidate right now that is estimated to be 15,000x more effective because of smart design to require 3 different mutations to survive, but those mutations don't work together.