TABLE 7.
Four multistep selection strains subcultured for 50 days
| Strain | Initial MIC(s) (μg/ml)b
|
Resistance selection
|
MIC (μg/ml) of strains resistant to:
|
Mutation(s) in QRDR of resistant mutanta
|
|||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DK-507k | Lev | Gati | Moxi | Sita | Cipro | Selecting agent | No. of passages | MIC (μg/ml) | DK-507k | Lev | Gati | Moxi | Sita | Cipro | GyrA | GyrB | ParC | ParE | |
| 1 | 0.5 | 16 | 4 | 4 | 0.25 | 32 | DK-507k | 50 | 8 | 8 | 128 | 16 | 16 | 4 | 256 | (E85K) | (S79F) + (K137N) | (I460V) | |
| Lev | 50 | 128 | 2 | 128 | 32 | 8 | 2 | 128 | (E85K) | (S79F) + (K137N) | (I460V) | ||||||||
| Gati | 50 | 128 | 32 | 256 | 128 | 125 | 16 | 256 | S81Y + (E85K) | (S79F) + D83G + (K137N) | (I460V) | ||||||||
| Moxi | 50 | 64 | 8 | 256 | 8 | 64 | 16 | 128 | (E85K) | (S79F) + (K137N) | D435N + (I460V) | ||||||||
| Sita | 50 | 8 | 8 | 64 | 16 | 16 | 8 | 64 | S81F + (E85K) | (S79F) + (K137N) | (I460V) | ||||||||
| Cipro | 50 | 1,024 | 2 | 64 | 2 | 8 | 2 | 1,024 | (E85K) | (S79F) + (K137N) | (I460V) | ||||||||
| 2 | 0.25 | 16 | 4 | 2 | 0.5 | 32 | DK-507k | 50 | 4 | 4 | 64 | 16 | 8 | 2 | 128 | (S81F) | R445S | (S79F) | (I460V) |
| Lev | 50 | 64 | 0.5 | 64 | 16 | 2 | 0.5 | 128 | (S81F) | (S79F) | (I460V) | ||||||||
| Gati | 50 | 16 | 2 | 64 | 16 | 16 | 2 | 64 | S81L | G406V | (S79F) | (I460V) | |||||||
| Moxi | 50 | 16 | 2 | 64 | 8 | 16 | 2 | 32 | S81V | A482G | (S79F) | (I460V) | |||||||
| Sita | 50 | 32 | 2 | 64 | 32 | 32 | 32 | 128 | E52D + S81V | (S79F) | (I460V) | ||||||||
| Cipro | 50 | 512 | 1 | 64 | 1 | 8 | 1 | 512 | E52D + (S81F) | (S79F) | (I460V) | ||||||||
| 4 | 0.03 | 1 | 0.25 | 0.12, 5 | 0.03 | 0.5 | DK-507k | 50 | 8 | 8 | 128 | 16 | 16 | 4 | 256 | (S81F) + G54A + V55N + A117S | E474K | (I460V) | |
| Lev | 50 | 16 | 0.125 | 16 | 4 | 2 | 0.25 | 32 | E85G | D83N | (I460V) + R447C | ||||||||
| Gati | 50 | 1 | 0.25 | 1 | 1 | 0.5 | 0.25 | 4 | (I460V) | ||||||||||
| Moxi | 50 | 4 | 0.5 | 32 | 1 | 4 | 1 | 64 | S81F | D83N | R447S + (I460V) | ||||||||
| Sita | 50 | 4 | 2 | 64 | 4 | 16 | 4 | 32 | S81Y | G486E | S79Y | (I460V) | |||||||
| Cipro | 50 | 512 | 2 | 64 | 1 | 8 | 2 | 512 | E85K | S79Y | (I460V) | ||||||||
| 5 | 0.03 | 0.5 | 0.25 | 0.125 | 0.03 | 0.5 | DK-507k | 50 | 1 | 1 | 16 | 0.5 | 4 | 1 | 32 | S81F | P454S | ||
| Lev | 50 | 4 | 0.125 | 4 | 0.5 | 0.5 | 0.25 | 8 | D83G | ||||||||||
| Gati | 50 | 0.5 | 0.25 | 8 | 0.5 | 0.5 | 0.25 | 8 | S81F | ||||||||||
| Moxi | 50 | 4 | 0.25 | 16 | 2 | 4 | 0.25 | 32 | E52D + S81Y | G406R | D83N | ||||||||
| Sita | 50 | 8 | 4 | 128 | 16 | 64 | 8 | 256 | S81Y + E85A | S79Y | |||||||||
| Cipro | 50 | 128 | 1 | 32 | 2 | 4 | 1 | 128 | S81F + G108A | S79Y | |||||||||
a
Mutations detected in parent strains are in parentheses; newly generated mutations are without parentheses.
b
Drug abbreviations are as for Table 3.