TABLE 3.
Log10 CFU counts and proportions of mice with M. tuberculosis-negative cultures at the end of treatment
| Groupa | Log10 CFU/lung (no. culture negative/total no. of animals)b |
|||||
|---|---|---|---|---|---|---|
| Initial | 4 wks | 6 wks | 8 wks | 10 wks | 12 wks | |
| None | 6.504 ± 0.155 | NT | NT | NT | NT | NT |
| Vehicle | NT | 6.454 ± 0.477 | 6.789 ± 0.329 | 6.761 ± 0.156 (0/5) | 6.654 ± 0.706 (0/4) | 6.491 ± 0.570 (0/5) |
| RHZE/RH | NT | 3.846 ± 0.123 | 2.704 ± 0.330 | 1.389 ± 0.800 (0/5) | 2.983 ± 0.697 (0/5) | 0.314 ± 0.701 (1/5) |
| DC | NT | 3.718 ± 0.412 | 3.083 ± 0.477 | 2.370 ± 0.183 (0/5) | 1.819 ± 0.069 (0/5) | 1.424 ± 0.195 (0/5) |
| DCLz | NT | 3.957 ± 0.236 | 3.290 ± 0.140 | 2.258 ± 0.281 (0/5) | 1.739 ± 0.202 (0/5) | 1.455 ± 0.183 (0/5) |
| DCM | NT | 2.520 ± 0.303 | 1.679 ± 0.442 | 0.298 ± 0.346 (0/5) | 0.077 ± 0.130 (1/4) | 0.000 ± 0.000 (5/5) |
| DCB | NT | 2.393 ± 0.380 | 1.409 ± 0.135 | 0.295 ± 0.445 (1/5) | 0.241 ± 0.538 (3/5) | 0.468 ± 0.807 (3/5) |
| DCLzM | NT | 3.221 ± 0.201 | 2.068 ± 0.382 | 0.328 ± 0.452 (1/4) | 0.075 ± 0.151 (2/4) | 0.012 ± 0.027 (4/4) |
| DCLzB | NT | 2.648 ± 0.253 | 1.618 ± 0.456 | 0.354 ± 0.415 (1/3) | 0.156 ± 0.348 (3/5) | 0.241 ± 0.392 (3/5) |
| DCMB | NT | 1.349 ± 0.004 | 1.352 ± 0.005 | 0.016 ± 0.022 (3/3) | 0.000 ± 0.000 (5/5) | 0.000 ± 0.000 (5/5) |
R, RIF (5 mg/kg); H, INH (25 mg/kg); Z, PZA (150 mg/kg); E, EMB (100 mg/kg); D, DMD (2.5 mg/kg); C, OPC-167832 (2.5 mg/kg); Lz, LZD (100 mg/kg); M, MXF (100 mg/kg); B, BDQ (25 mg/kg).
ICR female mice were intratracheally infected with M. tuberculosis Kurono, and chemotherapy was initiated 14 days after infection for 4, 6, 8, 10, or 12 weeks at 5 days per week (n = 5, except for one contaminated sample each in the DCMB group at 4 weeks and the DCLzM group at 10 weeks and one dead mouse in each of the vehicle groups at 6 and 10 weeks due to mistakes in administration [n = 4]). NT, not tested. For the RHZE group, mice received a combination treatment of RHZE for the initial 8 weeks, followed by further treatment with RH for 4 weeks. Each value represents the mean ± standard deviation (SD), which was calculated using the individual-mouse data. For mice with one or more contaminated plates but with the rest of the plates containing no M. tuberculosis, we used a detection limit methodology, as described in Materials and Methods. For detailed calculations of mouse data using this methodology, see Table S5 in the supplemental material. The proportions of mice that were culture negative (defined as no bacteria detected in any of the plates with lung homogenates) in the lungs are presented in parentheses. There were contaminated plates with lung homogenates from several mice: one each in the DCM 10-week, DCLzM 8-week, and DCLzM 12-week groups and two each in the DCLzB 8-week and DCMB 8-week groups. M. tuberculosis was not detected in the rest of the plates from these mice, and we excluded them from the values in parentheses.