Levofloxacin

Tryptic soy broth (TSB) was purchased from MilliporeSigma (Burlington, MA), Petri dishes, agar, and general supplies/reagents from Fisher Scientific (Hampton, NH), and brain heart infusion (BHI) broth from Research Products International (Mt Prospect, IL). CDC biofilm reactors and titanium (Ti) coupons were purchased from Biosurface Technologies (Bozeman, MT). Levofloxacin was acquired from Chem-Impex International (Wood Dale, IL) and rifampin from ThermoFisher Scientific (Waltham, MA).

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.