In light of recent research, the mechanisms and rates of
resistance, as well as the associated fitness costs and compensatory
mutations, should be investigated in the early stages of drug
development, as they provide relevant information about the
potential for the emergence, spread, and fixation of resistance
towards a particular drug. The ideal anti-TB drug would be one for
which resistance mutations are not only rare but also associated
with high fitness costs.96,97 In addition, it is important to identify
targets for which the rate of fitness-restoring mutations is low.
Restoration of fitness will be less likely when the fitness defect is
pleiotropic and affects more than one cellular process.97 The study
of the interactions between mutations conferring resistance to
different antibiotics (namely their combined effect on bacterial
fitness) could help optimize treatment regimens by identifying
those less likely to be associated with the emergence of multiple
drug resistance.