TABLE 2.
Frequencies of single-step mutation for 10 H. influenzae strains used for multistep study
| Strain | Selecting drug(s) | MICa (μg/ml) of drug
|
|||
|---|---|---|---|---|---|
| Initial | 2× | 4× | 8× | ||
| 1 | Amoxicillin-clavulanic acid | 0.5 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 |
| Cefpodoxime | 0.06 | 1.3 × 10−8 | <1.3 × 10−10 | <1.3 × 10−10 | |
| Cefprozil | 4 | 4.0 × 10−10 | <1.3 × 10−10 | <1.3 × 10−10 | |
| Azithromycin | 2 | <1.0 × 10−10 | <1.0 × 10−10 | <1.0 × 10−10 | |
| Clarithromycin | 8 | <1.0 × 10−10 | <1.0 × 10−10 | <1.0 × 10−10 | |
| 2 | Amoxicillin-clavulanic acid | 0.5 | <6.7 × 10−10 | <6.7 × 10−10 | <6.7 × 10−10 |
| Cefpodoxime | 0.06 | <1.3 × 10−10 | <1.3 × 10−10 | <1.3 × 10−10 | |
| Cefprozil | 2 | <2.0 × 10−10 | <2.0 × 10−10 | <2.0 × 10−10 | |
| Azithromycin | 1 | 4.0 × 10−9 | 2.0 × 10−9 | <2.0 × 10−10 | |
| Clarithromycin | 8 | 1.7 × 10−8 | 6.7 × 10−9 | 2.7 × 10−9 | |
| 3 | Amoxicillin-clavulanic acid | 0.5 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 |
| Cefpodoxime | 0.125 | <1.8 × 10−10 | <1.8 × 10−10 | <1.8 × 10−10 | |
| Cefprozil | 16 | 1.5 × 10−8 | <1.8 × 10−10 | <1.8 × 10−10 | |
| Azithromycin | 1 | 6.7 × 10−9 | <3.3 × 10−10 | <3.3 × 10−10 | |
| Clarithromycin | 8 | 5.0 × 10−9 | <5.0 × 10−10 | <5.0 × 10−10 | |
| 4 | Amoxicillin-clavulanic acid | 2 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 |
| Cefpodoxime | 0.06 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| Cefprozil | 128 | NDb | ND | ND | |
| Azithromycin | 1 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| Clarithromycin | 8 | 8.0 × 10−9 | <5.0 × 10−10 | <5.0 × 10−10 | |
| 5 | Amoxicillin-clavulanic acid | 1 | <3.3 × 10−10 | <3.3 × 10−10 | <3.3 × 10−10 |
| Cefpodoxime | 0.03 | <3.3 × 10−10 | <3.3 × 10−10 | <3.3 × 10−10 | |
| Cefprozil | 128 | ND | ND | ND | |
| Azithromycin | 1 | <3.3 × 10−10 | <3.3 × 10−10 | <3.3 × 10−10 | |
| Clarithromycin | 8 | <3.3 × 10−10 | <3.3 × 10−10 | <3.3 × 10−10 | |
| 6 | Amoxicillin-clavulanic acid | 0.5 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 |
| Cefpodoxime | 0.06 | <1.0 × 10−10 | <1.0 × 10−10 | <1.0 × 10−10 | |
| Cefprozil | 4 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| Azithromycin | 2 | 3.0 × 10−9 | <5.0 × 10−10 | <5.0 × 10−10 | |
| Clarithromycin | 4 | 5.0 × 10−9 | 1.0 × 10−9 | <5.0 × 10−10 | |
| 7 | Amoxicillin-clavulanic acid | 2 | <1.0 × 10−10 | <1.0 × 10−10 | <1.0 × 10−10 |
| Cefpodoxime | 0.125 | <1.0 × 10−10 | <1.0 × 10−10 | <1.0 × 10−10 | |
| Cefprozil | 128 | ND | ND | ND | |
| Azithromycin | 2 | 3.0 × 10−9 | 2.0 × 10−9 | 3.0 × 10−10 | |
| Clarithromycin | 8 | 2.0 × 10−9 | 2.0 × 10−10 | <1.0 × 10−10 | |
| 8 | Amoxicillin-clavulanic acid | 1 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 |
| Cefpodoxime | 0.06 | <5.0 × 10−10 | <5.0 × 10−10 | <5.0 × 10−10 | |
| Cefprozil | 64 | ND | ND | ND | |
| Azithromycin | 1 | 3.5 × 10−9 | <5.0 × 10−10 | <5.0 × 10−10 | |
| Clarithromycin | 8 | 1.5 × 10−9 | 1.5 × 10−9 | <5.0 × 10−10 | |
| 9 | Amoxicillin-clavulanic acid | 1 | <3.3 × 10−10 | <3.3 × 10−10 | <3.3 × 10−10 |
| Cefpodoxime | 0.06 | <3.3 × 10−10 | <3.3 × 10−10 | <3.3 × 10−10 | |
| Cefprozil | 8 | 6.7 × 10−8 | <3.3 × 10−10 | <3.3 × 10−10 | |
| Azithromycin | 2 | 1.0 × 10−9 | <3.3 × 10−10 | <3.3 × 10−10 | |
| Clarithromycin | 32 | 6.7 × 10−9 | 6.7 × 10−10 | <3.3 × 10−10 | |
| 10 | Amoxicillin-clavulanic acid | 0.5 | <1.3 × 10−10 | <1.3 × 10−10 | <1.3 × 10−10 |
| Cefpodoxime | 0.06 | <1.3 × 10−10 | <1.3 × 10−10 | <1.3 × 10−10 | |
| Cefprozil | 2 | <1.3 × 10−10 | <1.3 × 10−10 | <1.3 × 10−10 | |
| Azithromycin | 2 | <4.0 × 10−10 | <4.0 × 10−10 | <4.0 × 10−10 | |
| Clarithromycin | 16 | 1.3 × 10−9 | 6.3 × 10−10 | 2.5 × 10−10 | |
a
2×, 4×, and 8×, two, four, and eight times the MIC, respectively.
b
ND, not done. For strains 4, 5, 7, and 8, for which the MICs of cefprozil were high, no selection was done with cefprozil.