TABLE 4.
Combination treatment of HAMLET and erythromycin against erythromycin-resistant S. pyogenes and S. agalactiae clinical isolates
| Species and isolate | Erythromycin resistance gene(s) | Erythromycin MIC (μg/ml) |
Fold reduction (MIC) | |
|---|---|---|---|---|
| Without HAMLET | With HAMLETa | |||
| S. pyogenes | ||||
| 6 | mefA and msrD | 8 | 2 | 4 |
| 8 | mefA and msrD | 8 | 0.5 | 16 |
| 138 | mefA and msrD | 8 | 0.5 | 16 |
| 53 | ermB | 2,048 | 8 | 256 |
| 128 | ermB | 2,048 | 512 | 4 |
| 125 | ermTR | 32 | 2 | 16 |
| S. agalactiae | ||||
| 114 | ermB | >2,048 | 4 | >512 |
| 126 | ermB | >2,048 | 8 | >256 |
| 129 | ermB | >2,048 | 1,024 | >2 |
| 51 | ermTR | 16 | 1 | 16 |
| 113 | ermTR | 8 | 1 | 8 |
| 76 | Undetermined | 1,024 | 1 | 1,024 |
| 150 | Undetermined | 32 | 0.5 | 64 |
a
The MICs of HAMLET against the strains were similar between the isogenic mutants (50 and 125 μg/ml for GAS and GBS strains, respectively, with the HAMLET batch used). For the combination experiments, a sub-MIC concentration of HAMLET, representing 40 to 60% of the MIC (20 to 30 μg/ml for GAS strains and 30 to 75 μg/ml for GBS strains) was used.