Quinolones can enter cells easily and therefore are often used to treat intracellular pathogens. As there is a need for effective treatment and post-exposure prophylaxis, the objective of this study was to assess the in vitro susceptibilities

of these antibiotics with different modes of action and compare with efficacy in macrophages and mice infected with B. mallei. Results Susceptibility testing, MIC determination MICs were determined by the agar diffusion method and dilution method. The results from the agar diffusion method are listed in Tables 1 and 2. Our results indicate that B. mallei strain ATCC 23344 is click here Susceptible to a concentration as low as 10 μg/ml of ceftazidime and 25 μg/ml of levofloxacin comparable to our E. coli control strain. The MICs were further evaluated by the dilution Panobinostat purchase method for confirmation, resulting in 5 μg/ml of ceftazidime or 2.5 μg/ml of levofloxacin sufficient

to inhibit the growth of B. mallei in LBG after 18–24 h incubation at 37°C under shaking conditions. Table 1 Inhibition zone size standards for B. mallei for ceftazidime disks Disk potency (mg/ml) Zone diameter (mm) for B. mallei ATCC23344 Pattern of resistance/suceptibility 10 > 32 Susceptible 1 > 32 Susceptible 1 × 10-1 32 Susceptible 1 × 10-2 30 Susceptible 1 × 10-3 GW4869 19 Intermediate 1 × 10-4 < 1 Resistant 1 × 10-5 < 1 Resistant 1 × 10-6 < 1 Resistant Table 2 Inhibition zone size standards for B. mallei for levofloxacin disks Disk potency (mg/ml) Zone diameter (mm) for B. mallei ATCC23344 Pattern of resistance/susceptibility 2.5 > 40 Susceptible 2.5 × 10-1 > 40 Susceptible 2.5 × 10-2 27 Susceptible 2.5 × 10-3 10 Intermediatee 2.5 × 10-4 < 1 Resistant 2.5 × 10-5 < 1 Resistant 2.5 × 10-6 < 1 Resistant 2.5 × 10-7 < 1 Resistant In vivo post-exposure prophylaxis with levofloxacin and ceftazidime The confirmed challenge dose of B. mallei was 4.7 × 105 Ketotifen CFU per animal delivered i.n. in 50 μl PBS (25 μl per nare). Non-treated control animals became

sick within 48 h post-challenge indicated by non-specific signs such as piloerection and hypo-activity with trembling. The infection progressed with first deaths observed by day 4 post-challenge (Fig. 1). By day 6, 80% of non-treated control animals were dead with only one survivor in this group by day 34 (which lacked severe signs consistent with disease). Ceftazidime and levofloxacin, administrated i.p. 24 hours post-challenge, once a day, for 10 days, significantly reduced signs of the disease and proved to be effective with 100% survival rates at day 34 (P < 0.0001) on both treatments. Histological examination of organs from antibiotic treated survivors showed highly enlarged spleens with large, multifocal abscesses with extension into abdominal muscles in all infected animals (data not shown).