Table 2.
In vivo efficacy of single doses of JNJ-Q2 and comparators in a murine septicemia model with S. aureus Smith (MSSA) or OC 8525 (CA-MRSA)
| Compound, organism category, and dosing route (na) | ED50 in mg/kg/dayb (95% fiducial limits) | ED90 in mg/kg/dayc (95% fiducial limits) | P valued |
|---|---|---|---|
| JNJ-Q2 | |||
| MSSA | |||
| p.o. (24) | 2.0 (1.5-2.5) | 4.0 (3.2-7.9) | NA |
| s.c. (16) | 0.15 (0.05-0.22) | 0.4 (0.3-0.8) | NA |
| CA-MRSA | |||
| p.o. (16) | 12 (9.1-20.4) | 33.7 (21.1-108.6) | NA |
| s.c. (16) | 1.6 (1.0-2.2) | 5.4 (3.4-10.6) | NA |
| Ciprofloxacin | |||
| MSSA | |||
| p.o. (16) | 11 (6.5-41) | 31.0 (NL) | <0.0021 |
| s.c. (16) | 1.4 (0.92-2.5) | 3.3 (NL) | <0.0001 |
| Moxifloxacin | |||
| MSSA | |||
| p.o. (13) | 1.5 (0.73-2.2) | 3.1 (2.2-7.6) | >0.85 |
| s.c. (13) | 0.4 (0.2-0.8) | 2.8 (1.5-9.7) | <0.0001 |
| Gemifloxacin | |||
| MSSA | |||
| p.o. (21) | 1.1 (0.82-1.4) | 2.8 (1.4-3,036) | >0.14 |
| s.c. (13) | 0.1 (0.06-0.14) | 0.2 (0.15-0.45) | <0.0001 |
| Linezolide | |||
| CA-MRSA | |||
| p.o. (18) | 5.1 (3-8) | 16.6 (11.9-31.5) | <0.0087 |
| s.c. (18) | 3.7 (2-6) | 11.6 (8.3-22.8) | <0.0004 |
| Vancomycine | |||
| CA-MRSA | |||
| s.c. (32) | 12 (10-14) | 40.8 (29.1-69.4) | <0.0001 |
a
n, number of animals per group.
b
ED50s calculated using SAS version 5.
c
ED90s calculated using SAS version 9.1. NL, no limits obtained.
d
P values represent measurements of the significance of comparisons of dose-response profiles of survival incidence data for JNJ-Q2 and comparators. NA, not applicable.
e
Dosed BID, 1 and 3 h postinfection.