TABLE 5.

Fixation and elimination of drug resistance mutations carrying different costs of resistance

Cost of resistance (%)No. of generations for:
Fixation by compensatory mutationaEliminationb
29121,139
5359449
10175218
2083103
  • a Assuming a frequency of 10−6 of a compensatory mutation restoring fitness; the values are the number of generations (t) required for the compensated resistance genotype to become fixed, i.e., to represent 99% of the drug-resistant population, determined by the following formula: t = ln[(rct/rt)/(rct−1/rt−1)]/ln(1 − cost per generation), where rct and rct−1 are absolute numbers of resistant mutants with a compensatory mutation.

  • b Calculated for a ratio of resistant to susceptible organisms of 99:1 at time zero; the values are the number of generations (t) to reach levels of spontaneous drug resistance frequency (10−8) determined by the following formula: t = ln[10−8 (r0/S0)]/ln(1 − cost per generation).