Resistance Mutations Can Affect Pathogen Fitness

Accumulation of mutations can interfere with pathogen growth, that is, the mutations reduce fitness. In principle, reduced fitness could permit susceptible members of the population to overgrow the mutants when treatment with a particular antibiotic is halted. (Such a situation is often seen with HIV-1^131,132 and with several bacterial pathogens thought to acquire resistance through the use of animal growth promoters.¹³⁵) After a suitable wait, treatment with the antibiotic could be restarted. We do not know how long to withhold an antibiotic, because mutant subpopulations can remain at elevated levels, thereby facilitating rapid regrowth of resistant mutants when infections are re-exposed to the antibiotic. Moreover, loss of fitness can be corrected by yet another mutation, thereby enabling the mutant pathogen to regain fitness and also remain resistant. Cycling antibiotics has not solved the resistance problem.