INVITRO ACTIVITY OF T-3761, A NEW FLUOROQUINOLONE
INVITRO ACTIVITY OF T-3761, A NEW FLUOROQUINOLONE
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DOI：
10.1128/aac.36.10.2293
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发表时间：
1992-10-01
影响因子：
4.9
通讯作者：
MITSUHASHI, S
中科院分区：
文献类型：
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作者：
MURATANI, T;INOUE, M;MITSUHASHI, S
T-3761是一种新型氟喹诺酮类抗菌剂，具有C-10环丙基部分的恶嗪环结构，与其他药物对2，854种临床分离株的体外活性进行了比较。T-3761具有广谱活性，对革兰氏阳性菌和革兰氏阴性菌具有强效活性。T-3761对90%的甲氧西林敏感金黄色葡萄球菌、甲氧西林敏感和耐药表皮葡萄球菌和梭菌属的MIC。测试的是0.39至6.25 μ g/ml。其活性与环丙沙星和氧氟沙星相当，比诺氟沙星和氟罗沙星大4 - 8倍，但比托舒沙星小2 - 8倍。对环丙沙星耐药的S.金黄色葡萄球菌（环丙沙星的MIC，大于或等于3.13 μ g/ml）仍然对T-3761敏感（T-3761的MIC，小于或等于0.78 μ g/ml）。T-3761对90%供试链球菌和肠球菌的MIC为3.13 - 100 μ g/ml。其活性相当于或2-或4倍以上的诺氟沙星和氟罗沙星，相当于或2-或4倍以下的氧氟沙星和环丙沙星，和4- 16倍以下的托舒沙星。T-3761对革兰氏阴性菌的活性通常是诺氟沙星、氧氟沙星和氟罗沙星的四倍。许多对非氟喹诺酮类药物耐药的菌株，如米诺环素或亚胺培南耐药的S。金黄色葡萄球菌、耐头孢他啶的肠杆菌科成员、耐庆大霉素或亚胺培南的铜绿假单胞菌、耐氨苄青霉素的流感嗜血杆菌和淋病奈瑟菌对T-3761敏感。T-3761的MBC等于或大于MIC的两倍。在与1至4倍MIC的T-3761孵育期间，活细胞数迅速减少。在4倍MIC浓度下，T-3761对S.金黄色葡萄球菌、大肠杆菌、粘质沙雷氏菌和铜绿假单胞菌的检出率为2.2 x 10（-8）至小于或等于1.2 x 10（-9）。T-3761对E.大肠杆菌和铜绿假单胞菌分别为0.88和1.9 μ g/ml。
The in vitro activity of T-3761, a new fluoroquinolone antimicrobial agent which has an oxazine ring structure with a cyclopropyl moiety at C-10, was compared with those of other agents against 2,854 clinical isolates. T-3761 had a broad spectrum of activity and had potent activity against gram-positive and -negative bacteria. The MICs of T-3761 against 90% of the methicillin-susceptible Staphylococcus aureus, methicillin-susceptible and -resistant Staphylococcus epidermidis, and Clostridium spp. tested were 0.39 to 6.25 mug/ml. Its activity was comparable to those of ciprofloxacin and ofloxacin and four- to eightfold greater than those of norfloxacin and fleroxacin, but its activity was two- to eightfold less than that of tosufloxacin. Some isolates of ciprofloxacin-resistant S. aureus (MIC of ciprofloxacin, greater-than-or-equal-to 3.13 mug/ml) were still susceptible to T-3761 (MIC of T-3761, less-than-or-equal-to 0.78 mug/ml). The MICs of T-3761 against 90% of the streptococci and enterococci tested were 3.13 to 100 mug/ml. Its activity was equal to or 2- or 4-fold greater than those of norfloxacin and fleroxacin, equal to or 2- or 4-fold less than those of ofloxacin and ciprofloxacin, and 4- to 16-fold less than that of tosufloxacin. The activity of T-3761 against gram-negative bacteria was usually fourfold greater than those of norfloxacin, ofloxacin, and fleroxacin. Many isolates which were resistant to nonfluoroquinolone agents, such as minocycline- or imipenem-resistant S. aureus, ceftazidime-resistant members of the family Enterobacteriaceae, gentamicin- or imipenem-resistant Pseudomonas aeruginosa, and ampicillin-resistant Haemophilus influenzae and Neisseria gonorrhoeae, were susceptible to T-3761. The MBCs of T-3761 were either equal to or twofold greater than the MICs. The number of viable cells decreased rapidly during incubation with T-3761 at one to four times the MIC. At a concentration of four times the MIC, the frequencies of appearance of spontaneous mutants resistant to T-3761 against S. aureus, Escherichia coli, Serratia marcescens, and P. aeruginosa were 2.2 x 10(-8) to less-than-or-equal-to 1.2 x 10(-9). The 50% inhibitory concentrations of T-3761 for DNA gyrases isolated from E. coli and P. aeruginosa were 0.88 and 1.9 mug/ml, respectively.