In Vivo Efficacy of ABT-255 against Drug-Sensitive and -Resistant Mycobacterium tuberculosisStrains
In Vivo Efficacy of ABT-255 against Drug-Sensitive and -Resistant Mycobacterium tuberculosisStrains
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DOI：
10.1128/aac.42.10.2674
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发表时间：
1998-10
影响因子：
4.9
通讯作者：
A. Oleksijew;J. Meulbroek;Patty Ewing;K. Jarvis;M. Mitten;Lenette Paige;A. Tovcimak;Mike Nukkula;D. Chu;J. Alder
中科院分区：
文献类型：
--
作者：
A. Oleksijew;J. Meulbroek;Patty Ewing;K. Jarvis;M. Mitten;Lenette Paige;A. Tovcimak;Mike Nukkula;D. Chu;J. Alder
目前肺结核的治疗包括异烟肼、吡嗪酰胺、利福平、乙胺丁醇或链霉素治疗6个月，以获得可靠的治疗效果。较长的治疗期增加了不遵医嘱的可能性，导致产生耐多药结核分枝杆菌分离株。一种显著缩短疗程的治疗方案，或者一种对耐药结核分枝杆菌有效的新型抗菌药物，将是有价值的。ABT-255是一种新型的2-吡啶酮类抗菌剂，对药敏和耐药结核分枝杆菌具有体外效价和体内效价。Alamar蓝还原法测定ABT-255对结核分枝杆菌敏感菌株的MIC为0.016 ~ 0.031 μg/ml。ABT-255对耐利福平或乙胺丁醇结核分枝杆菌的MIC均为0.031 μg/ml。在小鼠肺结核模型中，口服ABT-255治疗4周后，肺组织中活的药物敏感结核分枝杆菌计数减少2至5 log10。针对耐药结核分枝杆菌菌株，ABT-255可使肺组织中活菌数量减少2- 3-log10。ABT-255是一种具有抗结核分枝杆菌活性的新型抗菌药物。
ABSTRACT 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 μg/ml. The MIC of ABT-255 against rifampin- or ethambutol-resistant M. tuberculosis isolates was 0.031 μg/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.