MALHOTRA S, GAUTAM R, BHADAURIYA T, RUDRA S, DAS B; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. F-2106.
Ranbaxy Research Laboratories, Gurgaon, India.
BACKGROUND: RBx 8700 is a new oxazolidinone with excellent in vitro activity against all slow growing Mycobacteria including M.tuberculosis. We investigated in vivo activity of RBx 8700 against M.tuberculosis ATCC 35801 (Erdman strain) systemic infection in target organ and survival model. Method: Mice were injected IV with 10[6] CFU/mouse. 24h later, 5 mice were sacrificed to determine baseline Mycobacterial load in target organs: Lungs and Spleen. Animals were divided into survival (Set I) and target organ (Set II) sets (n=8). Once daily oral treatment with RBx 8700, Rifampicin, Isoniazid, Ethambutol and PNU-100480 was initiated 24h post infection and continued 5d/wk for 4 wk (Set I) and 3 wk (Set II). Number of surviving animals was recorded daily. Mice from Set II were sacrificed 4d after completing treatment, target organs excised, homogenized in 0.05% tween saline and plated on OADC enriched Middlebrook 7H10 agar after serial dilutions. RESULTS: In Set I, 9 wk post treatment, RBx 8700 at 25mg/kg BW showed 100% survival that was comparable to Rifampicin and Isoniazid at same dose and PNU-100480 at 100 mg/kg BW, while superior to Ethambutol. In target organ, mean log CFU in untreated animals increased from 5.86 +/- 0.80 to 8.0 +/- 1.00 in lungs and 6.25 +/- 0.27 to 6.88 +/- 1.47 in spleen. For RBx 8700 treated mice mean log CFU in lungs was 2.81 +/- 1.17 and 2.50 +/- 0.71 in spleen. In Rifampicin treated mice CFU values were 2.35 +/- 0.46 and 2.21 +/- 0.40 in lungs and spleen respectively. Respective log CFU values (lungs/spleen) in Isoniazid, Ethambutol and PNU- 100480 treated groups were 3.87 +/- 0.88/3.53 +/- 0.79, 4.73 +/- 1.17/ 5.57 +/-1.11, 4.37 +/- 0.98/ 4.12 +/- 0.90. RBx 8700 thus showed the potential to cure experimental infection with M.tuberculosis, evidenced by reduction in CFU. Decrease in counts was in the order: RBx 8700 = Rifampicin > INH > Ethamutol = PNU 100480. CONCLUSIONS: RBx 8700 exhibited in vivo activity against experimental infection with M. tuberculosis which was superior to PNU-100480 and Ethambutol and comparable to Rifampicin and Isoniazid.
Publication Types:
Keywords:
- Animals
- Ethambutol
- In Vitro
- Isoniazid
- Lung
- Mice
- Mice, Inbred BALB C
- Muridae
- Mycobacterium
- Mycobacterium Infections
- Mycobacterium tuberculosis
- Oxazolidinones
- Rifampin
- Spleen
- Tuberculosis
Other ID:
UI: 102265802
From Meeting Abstracts