Pathogens that evolve
resistance to drugs usually have reduced fitness. However, mutations that largely compensate for this
reduction in fitness often arise. We investigate how these
compensatory mutations affect population-wide
resistance emergence as a function of drug treatment. Using a model of gonorrhea transmission dynamics, we obtain generally applicable, qualitative results that show how compensatory mutations lead to more likely and faster resistance emergence. We further show that resistance emergence depends on the level of drug use in a strongly nonlinear fashion. We also discuss what data need to be obtained to allow future quantitative predictions of resistance emergence.