TABLE 4.
Results of multipassage resistance selection by the dihydrophthalazine antifolates and comparators
| Strain (phenotype)a | Antibiotic | Initial MICb (μg/ml) | No. of passages | Final MIC |
|---|---|---|---|---|
| S. aureus ATCC 29213 (MSSA) | BAL0030543 | 0.03 | 50 | 8 |
| BAL0030544 | 0.06 | 50 | 0.5 | |
| BAL0030545 | 0.06 | 50 | 1 | |
| Trimethoprim | 1 | 14 | >128 | |
| Linezolid | 4 | 50 | 16 | |
| Minocycline | 0.125 | 50 | 2 | |
| Clindamycin | 0.125 | 50 | 32 | |
| Vancomycin | 1 | 50 | 4 | |
| Rifampin | 0.008 | 9 | >128 | |
| SA505 (MSSA, VISA) | BAL0030543 | 0.016 | 50 | 1 |
| BAL0030544 | 0.03 | 50 | 8 | |
| BAL0030545 | 0.03 | 50 | 2 | |
| Trimethoprim | 1 | 14 | >128 | |
| Linezolid | 4 | 50 | 16 | |
| Minocycline | 0.125 | 50 | 1 | |
| Clindamycin | 0.125 | 39 | >128 | |
| Vancomycin | 4 | 50 | 8 | |
| Rifampin | 0.016 | 9 | >128 | |
| S. aureus ATCC 43300 (MRSA) | BAL0030543 | 0.03 | 50 | 4 |
| BAL0030544 | 0.03 | 50 | 1 | |
| BAL0030545 | 0.06 | 50 | 2 | |
| Trimethoprim | 1 | 20 | >128 | |
| Linezolid | 2 | 50 | 64 | |
| Minocycline | 0.125 | 50 | 1 | |
| Clindamycin | >32 | |||
| Vancomycin | 1 | 50 | 4 | |
| Rifampin | 0.004 | 9 | >128 | |
| SA145 (MRSA) | BAL0030543 | 0.5 | 37 | >128 |
| BAL0030544 | 0.25 | 47 | >128 | |
| BAL0030545 | 0.25 | 50 | 128 | |
| Trimethoprim | >128 | |||
| Linezolid | 2 | 50 | 16 | |
| Minocycline | 4 | 50 | 8 | |
| Clindamycin | >32 | |||
| Vancomycin | 1 | 50 | 2 | |
| Rifampin | 0.008 | 10 | >128 | |
| VRS1 (MRSA, VRSA-MI) | BAL0030543 | 0.5 | 15 | >128 |
| BAL0030544 | 0.25 | 20 | >128 | |
| BAL0030545 | 1 | 25 | >128 | |
| Trimethoprim | >128 | |||
| Linezolid | 2 | 50 | 32 | |
| Minocycline | 0.5 | 50 | 2 | |
| Clindamycin | >32 | |||
| Vancomycin | >32 | |||
| Rifampin | >32 | |||
| CN051 (MSSE) | BAL0030543 | 0.25 | 50 | 64 |
| BAL0030544 | 0.125 | 38 | >128 | |
| BAL0030545 | 0.5 | 50 | 64 | |
| Trimethoprim | 64 | |||
| Linezolid | 2 | 50 | 128 | |
| Minocycline | 0.125 | 50 | 4 | |
| Clindamycin | 0.125 | 50 | 4 | |
| Vancomycin | 2 | 50 | 4 | |
| Rifampin | 0.008 | 9 | >128 | |
| CN057 (MSSE) | BAL0030543 | 8 | 50 | 128 |
| BAL0030544 | 8 | 15 | >128 | |
| BAL0030545 | 8 | 23 | >128 | |
| Trimethoprim | 128 | |||
| Linezolid | 2 | 50 | 64 | |
| Minocycline | 0.5 | 50 | 2 | |
| Clindamycin | 0.125 | 10 | >128 | |
| Vancomycin | 2 | 50 | 4 | |
| Rifampin | 0.016 | 9 | >128 | |
| CN197 (MRSE) | BAL0030543 | 0.03 | 50 | 1 |
| BAL0030544 | 0.06 | 50 | 0.125 | |
| BAL0030545 | 0.06 | 50 | 1 | |
| Trimethoprim | 1 | 50 | 64 | |
| Linezolid | 2 | 50 | 32 | |
| Minocycline | 0.125 | 50 | 2 | |
| Clindamycin | 0.125 | 50 | 2 | |
| Vancomycin | 2 | 50 | 4 | |
| Rifampin | 0.008 | 12 | >128 | |
| CN225 (MRSE, VISE) | BAL0030543 | 0.25 | 50 | 128 |
| BAL0030544 | 0.25 | 38 | >128 | |
| BAL0030545 | 0.25 | 36 | >128 | |
| Trimethoprim | >128 | |||
| Linezolid | 2 | 50 | 16 | |
| Minocycline | 0.125 | 50 | 1 | |
| Clindamycin | >32 | |||
| Vancomycin | 8 | 50 | 16 | |
| Rifampin | 0.016 | 11 | >128 | |
| CN345 (MRSE, LzdNS) | BAL0030543 | 0.125 | 50 | 16 |
| BAL0030544 | 0.06 | 33 | >128 | |
| BAL0030545 | 0.06 | 50 | 4 | |
| Trimethoprim | >128 | |||
| Linezolid | 32 | 50 | 128 | |
| Minocycline | 0.5 | 50 | 1 | |
| Clindamycin | 2 | 50 | 4 | |
| Vancomycin | 2 | 50 | 4 | |
| Rifampin | 0.008 | 9 | >128 |
a
Designations beginning with SA indicate S. aureus strains; VRS1 is a Michigan VRSA (VRSA-MI) strain. Designations beginning with CN indicate (coagulase-negative) S. epidermidis strains. MSSE, methicillin-susceptible S. epidermidis; MRSE, methicillin-resistant S. epidermidis; VISE, vancomycin-intermediate S. epidermidis.
b
Values in bold correspond to antibiotics for which serial passages of the indicated strain were not performed.