In vivo efficacy of ABT-255 against drug-sensitive and -resistant Mycobacterium tuberculosis strains

Current therapy for pulmonary tuberculosis involves 6 months of treatment with isoniazid, pyrazinamide, rifampin, and ethambutol or streptomycin for reliable treatment efficacy. The long treatment period increases the probability of noncompliance, leading to the generation of multidrug-resistant iso...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 1998-10, Vol.42 (10), p.2674-2677
Main Authors: OLEKSIJEW, A, MEULBROEK, J, EWING, P, JARVIS, K, MITTEN, M, PAIGE, L, TOVCIMAK, A, NUKKULA, M, CHU, D, ALDER, J. D
Format: Article
Language:English
Subjects:
Animals
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - therapeutic use
Biological and medical sciences
Drug Resistance, Microbial
Experimental Therapeutics
Female
Medical sciences
Mice
Mycobacterium tuberculosis
Pharmacology. Drug treatments
Pyridones - therapeutic use
Tuberculosis, Pulmonary - drug therapy
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Summary:Current therapy for pulmonary tuberculosis involves 6 months of treatment with isoniazid, pyrazinamide, rifampin, and ethambutol or streptomycin for reliable treatment efficacy. The long treatment period increases the probability of noncompliance, leading to the generation of multidrug-resistant isolates of Mycobacterium tuberculosis. A treatment option that significantly shortened the course of therapy, or a new class of antibacterial effective against drug-resistant M. tuberculosis would be of value. ABT-255 is a novel 2-pyridone antibacterial agent which demonstrates in vitro potency and in vivo efficacy against drug-susceptible and drug-resistant M. tuberculosis strains. By the Alamar blue reduction technique, the MIC of ABT-255 against susceptible strains of M. tuberculosis ranged from 0.016 to 0.031 microg/ml. The MIC of ABT-255 against rifampin- or ethambutol-resistant M. tuberculosis isolates was 0.031 microg/ml. In a murine model of pulmonary tuberculosis, 4 weeks of oral ABT-255 therapy produced a 2- to 5-log10 reduction in viable drug-susceptible M. tuberculosis counts from lung tissue. Against drug-resistant strains of M. tuberculosis, ABT-255 produced a 2- to 3-log10 reduction in viable bacterial counts from lung tissue. ABT-255 is a promising new antibacterial agent with activity against M. tuberculosis.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.42.10.2674