Both spleens and livers showed myeloid hyperplasia. C188-9 cost Interestingly, no lesions were found in the lungs of animals (data not shown). Figure 1 Percentage of survival of BALB/c mice challenged with 5 × 10

5 CFUs of B. mallei intranasally (n = 10). Treatment with antibiotic started 24 hours post-infection, once a day, for 10 days. Ceftazidime (X) and levofloxacin (○) were administrated i.p. in doses 100 mg/kg/day and 20 mg/kg/day respectively. 17DMAG The infection of B. mallei resulted in 90% death in non-treated animals (△). All antibiotic treated mice survived to day 34 post-infection. Experiment performed twice, P < 0.0001 for non-treated vs. antibiotic treated animals. Bacterial load at day 34 post-infection Harvested lungs and spleens from each group of animals challenged with 5 × 105 CFU/50 μl by i.n. route were subjected to plating on LBG for CFU determination per gram of organ weight. One animal from levofloxacin treatment was free of bacteria in spleen and liver. The spleen from this animal looked normal, was not enlarged, suggesting that in this particular case, infection was

not effective. Bacterial counts in the spleens from remaining antibiotic treated animals were similar, 1.9 × 104 ± 3.9 × 103 CFU/g for ceftazidime and 1.2 × 104 ± 6.6 × 103 CFU/g for levofloxacin and significantly lower from non-treated control animals (1.8 × 107 ± 8.6 × 106 CFU/g of spleen, Fig. 2). By day 34 post-infection, bacteria was largely cleared from the lungs with Pitavastatin no significant differences between antibiotic treated and non-treated animals, although bacterial

burden of the spleens suggested NADPH-cytochrome-c2 reductase that all animals developed chronic infection with B. mallei. Figure 2 Reduced B. mallei bacterial burden in antibiotic treated BALB/c mice. Thirty-four days post-challenge, surviving levofloxacin treated mice (black bars), ceftazidime treated mice (white bars) and untreated control mice (crossed bars) were euthanized, and lungs and spleens were harvested, weighed and serial dilutions plated for CFU/g tissue weight., * P < 0.05, ** P < 0.01. Errors bars represent mean ± SEM. The efficacy of ceftazidime and levofloxacin to kill intracellular bacteria in vitro For the determination of intracellular killing of B. mallei by antibiotics of interest, we performed a bacterial uptake assay by murine macrophages J774A.1 and evaluated bacterial killing for 8 hours of continuous exposure to antibiotics in concentrations equal to 100 × MIC for each compound tested. Murine J774A.1 cells were infected at an MOI of 25:1 and incubated for 2 hours in the absence of any antibiotics to allow for uptake (Time 0). At two hour intervals post-antibiotic exposure, intracellular CFU were determined resulting in a significant reduction of intracellular bacteria which continued throughout the assay (Fig. 3).