TABLE 4.
Activities of different drug regimens on P. carinii and T. gondii burdens in tissues in the rat model of concurrent pneumocystosis, toxoplasmosis, and M. avium complex infection
Drugs (dose [mg/kg])a | Outcome after T. gondii inoculationb | Day | No. of rats | Pleural fluid vol (ml) |
T. gondii count (log10)
|
P. carinii count (log10) in the lung | ||||
---|---|---|---|---|---|---|---|---|---|---|
Pleural fluid | Lung | Brain | Spleen | Liver | ||||||
None | Death | 5.7 ± 0.2 | 9/10c,d | 3.4 ± 1.8 | 3.6 ± 1.5 | 4.7 ± 1.9 | 3.7 ± 0.6 | 4.7 ± 1.0 | 6.1 ± 0.9 | 6.4 ± 0.6 |
CLA (200) and SMZ (20) | Sacrifice | 14 | 10 | 0 | 0e | 0e | 0e | 0e | 2.5 ± 0.5e | |
CLA (200) and ATO (100) | Sacrifice | 14 | 5 | 0 | 0e | 0e | 0e | 0e | 2.8 ± 0.5e | |
RIFA (100) and ATO (100) | Sacrifice | 14 | 5d,f | 0 | 0e | 0e | 0e | 0e | 2.8 ± 0.9e | |
ROX (200) and DAP (50) | Sacrifice | 14 | 5 | 0 | 0e | 0e | 0e | 0e | 2.5 ± 0.5e | |
ROX (200) and SMZ (20) | Sacrifice | 14 | 5 | 0 | 0e | 0e | 0e | 0e | 2.4 ± 0.5e | |
PS-15 (25) and DAP (25) | Sacrifice | 14 | 5d,g | 0 | 0e | 0e | 0.3 ± 0.7e | 0e | 2.5 ± 0.6e | |
TMP (20) and SMZ (100) | Sacrifice | 14 | 5 | 0 | 0e | 0e | 0e | 0e | 2.7 ± 0.7e |
The drugs clarithromycin (CLA), sulfamethoxazole (SMZ), atovaquone (ATO), rifabutin (RIFA), roxithromycin (ROX), dapsone (DAP), PS-15, and trimethoprim (TMP) were given per os 5 days per week for 5 weeks and daily after T. gondii inoculation (at week 5) until death or sacrifice.
T. gondii tachyzoites were inoculated intraperitoneally after 5 weeks of immunosuppression. Sacrifice indicates that the rats were killed by the investigators.
One rat survived and was sacrificed at day 14.
The levels of infections detected were similar to those found after the other rats were killed and the values were pooled.
P < 0.01 compared to the values for untreated controls.
One rat died after a gavage at day 11.
One rat died from bacterial infection at day 13.