Smallpox was eliminated through a vaccine campaign. Resistance against vaccines is generally different from resistance from treatments. For example, since vaccines are in place pre-infection, the amount of target microbes in the body at time of action is pretty low, giving a much higher chance of killing them all. Treatment is usually given after infection, where there will be a large amount of target microbes. This will substantially increase the probability some critter surviving with more resistance genes and then passing them on.