Table 3.

FRE in S. aureus ISP794 selected by BMS-284756 and ciprofloxacin

Multiple of MIC usedFRE for BMS-284756 or ciprofloxacina
BMS-284756Ciprofloxacin
For first-step mutants
 2× MIC for parental strain>8.0 × 10−10   5 × 10−10 >1.5 × 10−7 >6.8 × 10−7
 4× MIC for parental strain 8.0 × 10−10 NDc 1.5 × 10−7 6.8 × 10−7
 8× MIC for parental strainNDNDNDNone
For second-step mutants
 2× MIC for first-step mutant 1.4 × 10−9 1.2 × 10−9 1.3 × 10−8 1.7 × 10−8
 4× MIC for first-step mutantNoneNoneNoneNone
 8× MIC for first-step mutantNoneNDNDNone
For third-step mutantsb
 2× MIC for second-step mutant>1.3 × 10−9, >8.3 × 10−9 >4.5 × 10−9, >1.3 × 10−8 1.2 × 10−8 2.2 × 10−7
 4× MIC for second-step mutant 1.3 × 10−9, 8.3 × 10−9 4.5 × 10−9, 1.3 × 10−8 NoneNone
 8× MIC for second-step mutantNoneNoneNDND
For fourth-step mutants
 2× MIC for third-step mutant>2.6 × 10−7, >1.3 × 10−8 >2.5 × 10−7, >6.25 × 10−9 5.8 × 10−6 1.2 × 10−6
 4× MIC for third-step mutant>2.6 × 10−7, >1.3 × 10−8 >2.5 × 10−7, >6.25 × 10−9 NoneNone
 8× MIC for third-step mutant 2.6 × 10−7, >1.3 × 10−8 2.5 × 10−7, >6.25 × 10−9 NDNone
 16× MIC for third-step mutantND, 1.3 × 10−8 ND, 6.25 × 10−9 NDND
  • a FREs were determined in two separate experiments for each drug; results from both trials are shown in the two columns.

  • b Two BMS-284756 mutants were carried forward (designated no. 6 and 10) for third- and fourth-step mutants. Each frequency was repeated twice. The first column under BMS-284756 represents mutants 6A and 6B, and the second column represents mutants 10A and 10B.

  • c ND, not determined.