IN-VIVO EFFICACY OF ABT-255 AGAINST DRUG-SENSITIVE AND DRUG-RESISTANTMYCOBACTERIUM-TUBERCULOSIS STRAINS

Current therapy for pulmonary tuberculosis involves 6 months of treatm ent with isoniazid, pyrazinamide, rifampin, and ethambutol or streptom ycin for reliable treatment efficacy. The long treatment period increa ses the probability of noncompliance, leading to the generation of mul tidrug-resistant isolates of Mycobacterium tuberculosis. A treatment o ption that significantly shortened the course of therapy, or a new cla ss of antibacterial effective against drug-resistant M. tuberculosis w ould be of value, ABT-255 is a novel 2-pyridone antibacterial agent wh ich demonstrates in vitro potency and in vivo efficacy against drug-su sceptible and drug-resistant M. tuberculosis strains. By the Alamar bl ue reduction technique, the MIC of ABT-255 against susceptible strains of M. tuberculosis ranged from 0.016 to 0.031 mu g/ml, The MIC of ABT -255 against rifampin- or ethambutol-resistant nl. tuberculosis isolat es was 0.031 mu g/ml, In a murine model of pulmonary tuberculosis, 4 w eeks of oral ABT-255 therapy produced a 2- to 5-log(10) reduction in v iable drug-susceptible Rt tuberculosis counts from lung tissue. Agains t drug-resistant strains of RI. tuberculosis. ABT-255 produced a 2- to 3-log(10) reduction in viable bacterial counts from lung tissue. ABT- 255 is a promising new antibacterial agent with activity against M. tu berculosis.