Microorganisms have been using antibiotics against each other since life begun on Earth and have evolved ways to evolve around them and develop resistance. For a drug to become ineffective, its target needs a possible evolutionary path around its effect. Depending on what the drug effect, it's possible such path does not exist.

Of course, as Jeff Goldblum wisely said, life always finds a way. We can only hope it takes a long time for that to happen.