TABLE 2.
Effects of antibiotics on S. aureus membrane integrity and skin fibroblast cells measured by various assays
| Antibiotic (MIC [μg/ml])a | Absorbance of culture filtrate at 260 nma | MIC (μg/ml) against S. aureus 8235 in DMEMb | Cytotoxic IC50 (μg/ml) against CCD-32Sk in DMEMb | Therapeutic indexc |
|---|---|---|---|---|
| 867 (0.8) | 0.012 ± 0.006 | 25 | 308.4 | 12.3 |
| 1135 (0.8) | 0.065 ± 0.021 | 25 | 356 | 14.4 |
| 1137 (0.8) | 0.041 ± 0.033 | 25 | 529.1 | 21.2 |
| 1138 (1.6) | 0.043 ± 0.023 | 25 | 376.8 | 15.1 |
| 1139 (0.8) | 0.023 ± 0.006 | 25 | 256.1 | 10.2 |
| Reutericyclin (1.6) | 0.05 ± 0.023 | 25 | 263.6 | 10.5 |
| Nisin (12.5) | 0.231 ± 0.047 | NAd | NA | NA |
| Amoxicillin (0.1) | 0.046 ± 0.02 | NA | NA | NA |
S. aureus 8325 resuspended in phosphate-buffered saline was exposed to antibiotics at 4× their Mueller-Hinton broth MICs for 1 h before measuring the absorbance of leaked cellular material at an optical density at 260 nm in the culture filtrate.
Both MICs and cytotoxicities were evaluated in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum to allow direct determination of the therapeutic index.
The therapeutic index was calculated as the cytotoxic 50% inhibitory concentration (IC50)/MIC. Estimated therapeutic indices for vancomycin and mupirocin were >25,000 and >1,600, respectively, since the respective MICs in DMEM were 0.8 and 12.5 μg/ml and the cytotoxic IC50s were both >20,000 μg/ml.
NA, not assessed.