TABLE 3.
Results of multistep resistance selection studiesa
| Strain; description | Antibiotic | Initial MIC (μg/ml) | MIC (μg/ml) after resistance selection (no. of passages) | MIC after 10 antibiotic-free subcultures for:
|
||||
|---|---|---|---|---|---|---|---|---|
| CG400549 | Daptomycin | Linezolid | Quinupristin-dalfopristin | Vancomycin | ||||
| SA481; CAMRSA, PVL neg | CG400549 | 0.25 | 2 (14) | 2 | 1 | 4 | 0.25 | 2 |
| Daptomycin | 1 | 8 (14) | 0.25 | 8 | 4 | 0.25 | 4 | |
| Linezolid | 4 | 32 (37) | 0.125 | 1 | 32 | 0.5 | 2 | |
| Quinupristin-dalfopristin | 0.25 | 2 (16) | 0.25 | 1 | 4 | 2 | 2 | |
| Vancomycin | 2 | 8 (50) | NT | NT | NT | NT | NT | |
| SA490; CAMRSA, PVL pos | CG400549 | 0.25 | 8 (17) | 8 | 1 | 4 | 0.25 | 2 |
| Daptomycin | 1 | 8 (14) | 0.25 | 4 | 4 | 0.125 | 2 | |
| Linezolid | 4 | 32 (22) | 0.25 | 1 | 32 | 0.25 | 2 | |
| Quinupristin-dalfopristin | 0.25 | 4 (23) | 0.125 | 1 | 4 | 4 | 2 | |
| Vancomycin | 2 | 8 (50) | NT | NT | NT | NT | NT | |
| SA504; VISA | CG400549 | 0.25 | 2 (14) | 2 | 1b | 2 | 0.5 | 2b |
| Daptomycin | 4 | 16 (50) | NT | NT | NT | NT | NT | |
| Linezolid | 1 | 8 (22) | 0.25 | 1b | 8 | 0.5 | 8 | |
| Quinupristin-dalfopristin | 0.25 | 2 (16) | 0.5 | 2 | 2 | 2 | 2b | |
| Vancomycin | 8 | 8 (50) | NT | NT | NT | NT | NT | |
| SA509; VRSA, from Michigan | CG400549 | 1 | >64 (14) | >64 | 1 | 2 | 0.5 | 16b |
| Daptomycin | 1 | 8 (20) | 1 | 4 | 2 | 0.5 | 32b | |
| Linezolid | 2 | 16 (28) | 0.5 | 2 | 32 | 1 | >64 | |
| Quinupristin-dalfopristin | 0.5 | 4 (18) | 1 | 1 | 4 | 4 | 4b | |
| Vancomycin | >64 | NT | NT | NT | NT | NT | NT | |
| SA510; VRSA, from Hershey | CG400549 | 0.25 | 4 (14) | 4 | 1 | 2 | 0.25 | 16b |
| Daptomycin | 1 | 8 (18) | 0.125 | 4 | 4 | 0.25 | 2b | |
| Linezolid | 4 | 16 (50) | NT | NT | NT | NT | NT | |
| Quinupristin-dalfopristin | 0.25 | 4 (14) | 0.25 | 0.5 | 4 | 4 | 2b | |
| Vancomycin | 64 | NT | NT | NT | NT | NT | NT | |
| SA525; MRSA | CG400549 | 0.25 | 4 (14) | 4 | 1 | 4 | 0.25 | 1 |
| Daptomycin | 1 | 8 (20) | 0.125 | 2c | 4 | 0.25 | 2 | |
| Linezolid | 4 | 16 (50) | NT | NT | NT | NT | NT | |
| Quinupristin-dalfopristin | 0.25 | 2 (16) | 0.125 | 1 | 4 | 2 | 1 | |
| Vancomycin | 2 | 8 (50) | NT | NT | NT | NT | NT | |
| SA547; MRSA | CG400549 | 0.125 | 32 (14) | 8c | 1 | 4 | 0.25 | 2 |
| Daptomycin | 1 | 8 (21) | 0.125 | 4 | 4 | 0.25 | 4 | |
| Linezolid | 4 | 32 (48) | 0.125 | 2 | 32 | 0.5 | 2 | |
| Quinupristin-dalfopristin | 0.25 | 2 (21) | 0.125 | 1 | 4 | 2 | 2 | |
| Vancomycin | 2 | 8 (50) | NT | NT | NT | NT | NT | |
| SA555; VISA, from Hershey | CG400549 | 0.25 | 2 (14) | 2 | 8 | 2 | 0.06 | 8 |
| Daptomycin | 16 | 32 (50) | NT | NT | NT | NT | NT | |
| Linezolid | 2 | 4 (50) | NT | NT | NT | NT | NT | |
| Quinupristin-dalfopristin | 0.125 | 1 (20) | 0.25 | 2b | 4 | 0.5 | 2b | |
| Vancomycin | 8 | 8 (50) | NT | NT | NT | NT | NT | |
| SA540; MSSA | CG400549 | 0.125 | 16 (14) | 4c | 1 | 4 | 0.25 | 2 |
| Daptomycin | 1 | 8 (24) | 0.125 | 2c | 4 | 0.25 | 4 | |
| Linezolid | 4 | 32 (36) | 0.125 | 2 | 16 | 0.5 | 4 | |
| Quinupristin-dalfopristin | 0.25 | 2 (16) | 0.125 | 2 | 4 | 2 | 2 | |
| Vancomycin | 4 | 8 (50) | NT | NT | NT | NT | NT | |
| SA543; MSSA | CG400549 | 0.125 | 8 (14) | 8 | 1 | 4 | 0.25 | 1 |
| Daptomycin | 1 | 8 (17) | 0.125 | 4 | 4 | 0.25 | 2 | |
| Linezolid | 4 | 32 (15) | 0.125 | 2 | 32 | 0.25 | 2 | |
| Quinupristin-dalfopristin | 0.25 | 2 (18) | 0.125 | 2 | 4 | 2 | 4 | |
| Vancomycin | 2 | 8 (50) | NT | NT | NT | NT | NT | |
a
CAMRSA, community-acquired MRSA; NT, not tested. neg, negative; pos, positive.
b
MIC for mutant was ≥2 dilutions lower than MIC for parent.
c
MIC for mutant was 2 dilutions lower than its MIC after resistance selection was performed.