Female New Zealand White (NZW) rabbits (Millbrook Farm, Concord, MA), weighing 2.2 to 2.6 kg, were maintained under specific pathogen-free conditions and fed water and chow ad libitum. The rabbits were infected with M. tuberculosis HN878, using a nose-only aerosol exposure system as described (Subbian et al., 2011 (link)). Three hours post-infection, one rabbit from each round of infection was sacrificed to determine the bacterial load implanted in the lungs. At defined time points from 16 to 20 weeks post-infection, rabbits received a single dose of 100 mg/kg moxifloxacin (Chemieliva Pharmaceuticals, China), 75 mg/kg levofloxacin or 100 mg/kg gatifloxacin (Chem-Impex Intl, IL), formulated in 40% sucrose and PEG400 (90:10) by oral gavage. The time points post infection were selected to ensure that mature necrotic granulomas had formed and reached a size sufficient to allow dissection and imaging of individual lesions. Blood was collected from the central ear artery of each rabbit pre-dose, and at several time points between drug administration and necropsy. Rabbits were euthanized at 2 to 12 hr post-dose, or between the time of peak plasma concentration and the end of the tissue distribution phase.
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