TABLE 1.
Results of macromolecular labeling studies for effects of cadazolid and reference antibiotics on incorporation of [3H]-l-leucine (protein synthesis), [3H]-l-adenine (nucleic acid synthesis), and N-acetyl-d-[6-3H]glucosamine (cell wall synthesis) in different C. difficile strainsa
| Test | Strain (phenotype) | Cadazolid | Linezolid | Moxifloxacin | Vancomycin |
|---|---|---|---|---|---|
| Inhibition of protein synthesis IC50 | ATCC 43602 (LZDs, FQs) | 0.09 (0.08–0.10) | 1.7 (1.4–2.0) | >64 | ND |
| NCTC 13366 (LZDs, FQr) | 0.08 (0.07–0.09) | 1.8 (1.5–2.1) | >64 | ND | |
| A-1291 (LZDr, FQs) | 0.19 (0.17–0.21) | 11.8 (9.2–15) | >64 | ND | |
| A-1410 (LZDr, FQr) | 0.31 (0.27–0.36) | 68.0 (51–89) | >32 | ND | |
| Inhibition of nucleic acid synthesis IC50 | ATCC 43602 (LZDs, FQs) | 12.0 (7.0–20.4) | >128 | 2.4 (1.9–2.9) | ND |
| NCTC 13366 (LZDs, FQr) | 17.6 (12.7–24.3) | >128 | 46 (31.6–68) | ND | |
| A-1291 (LZDr, FQs) | 14.3 (8.4–24.5) | >128 | 6.0 (4.5–7.9) | ND | |
| A-1410 (LZDr, FQr) | 18.6 (9.4–36.9) | >128 | 43.0 (8.0–231) | ND | |
| Inhibition of cell wall synthesis IC50 | ATCC 43602 (LZDs, FQs) | >32 | ND | ND | 1.4 (0.89–2.3) |
| A-1410 (LZDr, FQr) | >32 | ND | ND | 4.7 (3.2–6.8) | |
| MIC | ATCC 43602 (LZDs, FQs) | 0.125–0.25 | 2 | 2 | 1 |
| NCTC 13366 (LZDs, FQr) | 0.125–0.25 | 1 | 32 | 1 | |
| A-1291 (LZDr, FQs) | 0.25–0.5 | 16–32 | 1 | 2 | |
| A-1410 (LZDr, FQr) | 0.5 | 32–64 | 32 | 1 |
a
Values are in μg/ml; for IC50s, 95% confidence intervals are given in parentheses. LZDs, linezolid susceptible; LZDr, linezolid resistant; FQs, fluoroquinolone susceptible; FQr, fluoroquinolone resistant; ND, not determined.