TABLE 1.
Multistep resistance selection studies
| Strain | β-Lactamase | Selecting drug(s) | No. of passages | MIC (μg/ml) of drug for parent and selected strains after 10 antibiotic-free subcultures
|
||||
|---|---|---|---|---|---|---|---|---|
| Amoxicillin-clavulanic acid | Cefpodoxime | Cefprozil | Azithromycin | Clarithromycin | ||||
| 1 | − | 0.5 | 0.06 | 4 | 2 | 8 | ||
| Amoxicillin-clavulanic acid | 50 | —a | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | 32 | 0.5 | 0.06 | 64 | 4 | 16 | ||
| Azithromycin | 29 | 0.5 | 0.06 | 8 | 32 | 64 | ||
| Clarithromycin | 14 | 0.5 | 0.03 | 4 | 64 | 128 | ||
| 2 | − | 0.5 | 0.06 | 2 | 1 | 8 | ||
| Amoxicillin-clavulanic acid | 50 | — | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | 50 | — | — | — | — | — | ||
| Azithromycin | 29 | 0.5 | 0.06 | 2 | >128 | >128 | ||
| Clarithromycin | 24 | 0.5 | 0.06 | 2 | 16 | 128 | ||
| 3 | − | 0.5 | 0.125 | 16 | 1 | 8 | ||
| Amoxicillin-clavulanic acid | 50 | — | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | 50 | — | — | — | — | — | ||
| Azithromycin | 22 | 0.5 | 0.125 | 32 | 64 | 64 | ||
| Clarithromycin | 32 | 1 | 0.125 | 8 | 8 | 64 | ||
| 4 | + | 2 | 0.06 | 128 | 1 | 8 | ||
| Amoxicillin-clavulanic acid | 50 | — | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | NDb | |||||||
| Azithromycin | 50 | 1 | 0.06 | 64 | 32 | 64 | ||
| Clarithromycin | 50 | — | — | — | — | — | ||
| 5 | + | 1 | 0.03 | 128 | 1 | 8 | ||
| Amoxicillin-clavulanic acid | 50 | — | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | ND | |||||||
| Azithromycin | 23 | 1 | 0.03 | 32 | 16 | 64 | ||
| Clarithromycin | 24 | 1 | 0.03 | 16 | >128 | >128 | ||
| 6 | − | 0.5 | 0.06 | 4 | 2 | 4 | ||
| Amoxicillin-clavulanic acid | 50 | — | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | 50 | — | — | — | — | — | ||
| Azithromycin | 49 | 0.5 | 0.06 | 2 | 16 | 64 | ||
| Clarithromycin | 46 | 0.5 | 0.06 | 2 | 8 | 32 | ||
| 7 | + | 2 | 0.125 | 128 | 2 | 8 | ||
| Amoxicillin-clavulanic acid | 50 | — | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | ND | |||||||
| Azithromycin | 22 | 2 | 0.125 | 32 | >128 | >128 | ||
| Clarithromycin | 50 | |||||||
| 8 | + | 1 | 0.06 | 64 | 1 | 8 | ||
| Amoxicillin-clavulanic acid | 50 | — | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | 50 | — | — | — | — | — | ||
| Azithromycin | 24 | 1 | 0.125 | >128 | 16 | 32 | ||
| Clarithromycin | 14 | 2 | 0.125 | >128 | 32 | 128 | ||
| 9 | + | 1 | 0.06 | 8 | 2 | 32 | ||
| Amoxicillin-clavulanic acid | 50 | — | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | 50 | — | — | — | — | — | ||
| Azithromycin | 20 | 1 | 0.25 | 4 | 16 | >128 | ||
| Clarithromycin | 32 | 1 | 0.03 | 16 | 32 | >128 | ||
| 10 | − | 0.5 | 0.06 | 2 | 2 | 16 | ||
| Amoxicillin-clavulanic acid | 50 | — | — | — | — | — | ||
| Cefpodoxime | 50 | — | — | — | — | — | ||
| Cefprozil | 50 | — | — | — | — | — | ||
| Azithromycin | 32 | 0.5 | 0.125 | 2 | >128 | >128 | ||
| Clarithromycin | 14 | 0.5 | 0.06 | 2 | 16 | 128 | ||
a
—, no mutant was selected after 50 days of subculture.
b
ND, not done. For three strains for which the MICs of cefprozil were >128 μg/ml, no selection was done.