TABLE 3.
Efficacies of ABT-773 and comparative agents in experimental S. pneumoniae-associated lung infections in rats
| S. pneumoniae strain (characteristic) and compound | Daily dosee (mg/kg) | MIC (μg/ml) | Log10 CFU/lung (mean ± SE) | Pg | ED50h (95% confidence limits)
|
|
|---|---|---|---|---|---|---|
| 2-log10 reduction | 3-log10 reduction | |||||
| 6303 (MLSBs)a | ||||||
| Vehicle controld | NAi | NA | 8.13 ± 0.08 | NA | NA | |
| ABT-773 | 0.6 | 0.001 | 5.89 ± 0.67 | 0.029 | <0.6 (NC)j | 1.2 (1.2–1.3) |
| 2.5 | 3.45 ± 0.25 | <0.001 | ||||
| 10 | 3.27 ± 0.19 | <0.001 | ||||
| Azithromycin | 3.1 | 0.03 | 6.38 ± 0.52 | 0.027 | 3.7 (2.3–5.9) | 6.0 (3.8–9.6) |
| 12.5 | 2.33 ± 0.82 | 0.002 | ||||
| 50 | 1.14 ± 0.47 | <0.001 | ||||
| Clarithromycinf | 3.1 | 0.008 | 6.38 ± 0.85 | 0.109 | 3.7 (2.3–6.2) | 6.2 (3.8–10.3) |
| 12.5 | 2.60 ± 0.82 | 0.002 | ||||
| 50 | 2.33 ± 0.15 | <0.001 | ||||
| 5649 (mefE)b | ||||||
| Vehicle control | NA | NA | 5.37 ± 0.47 | NA | NA | |
| ABT-773 | 1.25 | 0.06 | 4.99 ± 0.70 | 0.65 | 11.8 (6.6–21.1) | 15.1 (8.4–27.1) |
| 5 | 5.39 ± 0.97 | 0.98 | ||||
| 20 | 0.92 ± 0.57 | <0.001 | ||||
| Azithromycin | 6.3 | 8 | 6.20 ± 0.70 | 0.26 | 24.9 (20.7–30.1) | 78.7 (62.2–99.5) |
| 25 | 3.37 ± 0.46 | 0.019 | ||||
| 100 | 1.98 ± 0.53 | <0.001 | ||||
| Clarithromycin | 6.3 | 4 | 4.66 ± 0.22 | 0.37 | 41.9 (39.3–44.7) | 69.7 (65.3–74.3) |
| 25 | 3.98 ± 0.35 | 0.083 | ||||
| 100 | 1.28 ± 0.55 | <0.001 | ||||
| 6396 (ermB)c | ||||||
| Vehicle control | NA | NA | 6.48 ± 0.31 | NA | NA | |
| ABT-773 | 0.6 | 0.015 | 4.75 ± 0.39 | 0.006 | 1.0 (0.6–1.6) | 2.3 (1.4–3.7) |
| 2.5 | 3.29 ± 0.07 | <0.001 | ||||
| 10 | 2.81 ± 0.28 | <0.001 | ||||
| Azithromycin | 10 | >128 | 6.75 ± 0.59 | 0.66 | >100 (NC) | >100 (NC) |
| 30 | 5.55 ± 0.59 | 0.14 | ||||
| 100 | 7.39 ± 0.63 | 0.17 | ||||
| Clarithromycin | 10 | >128 | 5.78 ± 0.64 | 0.28 | >100 (NC) | >100 (NC) |
| 30 | 6.61 ± 0.29 | 0.79 | ||||
| 100 | 7.76 ± 0.13 | 0.003 | ||||
Intratracheal inoculum of log10 5.8.
Intratracheal inoculum of log10 7.2.
Intratracheal inoculum of log10 5.9.
Vehicle-treated infected control rats were dosed orally for 3 days.
Rats were orally dosed daily for 3 days, starting 18 h postinfection.
Clarithromycin total daily dose given half strength 12 h apart.
Statistical difference for comparison with result for untreated control, determined by the t test or Mann-Whitney U test.
The ED50 (in milligrams per kilogram per day) to produce a 2- or 3-log10 reduction in bacterial count compared to the vehicle-treated controls using linear regression of the group means.
NA, not applicable.
NC, not calculated.