In vivo efficacy of biapenem with ME1071, a novel metallo-β-lactamase (MBL) inhibitor, in a murine model mimicking ventilator-associated pneumonia caused by MBL-producing Pseudomonas aeruginosa.
In vivo efficacy of biapenem with ME1071, a novel metallo-β-lactamase (MBL) inhibitor, in a murine model mimicking ventilator-associated pneumonia caused by MBL-producing Pseudomonas aeruginosa.
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比阿培南与 ME1071（一种新型金属β-内酰胺酶 (MBL) 抑制剂）在模拟由产生 MBL 的铜绿假单胞菌引起的呼吸机相关性肺炎的小鼠模型中的体内疗效。
DOI：
10.1016/j.ijantimicag.2013.05.016
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发表时间：
2013
影响因子：
10.8
通讯作者：
S. Kohno
中科院分区：
文献类型：
--
作者：
Koichi Yamada;K. Yanagihara;N. Kaku;Y. Harada;Y. Migiyama;K. Nagaoka;Y. Morinaga;Shigeki Nakamura;Y. Imamura;T. Miyazaki;K. Izumikawa;H. Kakeya;H. Hasegawa;A. Yasuoka;S. Kohno
ME 1071是一种新型的金属β-内酰胺酶（MBLs）特异性抑制剂。ME 1071可增强碳青霉烯类抗生素对产MBL铜绿假单胞菌的体外抗菌活性。目的：观察ME 1071对产MBL肺炎球菌所致呼吸机相关性肺炎（VAP）的临床疗效。在铜绿假单胞菌中，使用通过在支气管中放置塑料管来模拟VAP的小鼠模型。从接种后12小时开始，每12小时腹膜内施用比阿培南（100 mg/kg）或ME 1071加比阿培南（各100 mg/kg）。在7天内评价存活率。在感染后30 h，处死小鼠，比较肺和支气管肺泡灌洗液（BALF）中的活菌数。还对肺标本进行了组织学分析。在初始治疗后分析ME 1071的药代动力学。ME 1071联合比阿培南组生存期明显长于对照组和比阿培南单药组（P< 0.05）。联合用药组肺内活菌数明显低于对照组（P< 0.05）。肺标本的组织学检查表明，联合用药组可预防肺部炎症的进展。联合用药组BALF中细胞总数、中性粒细胞计数及细胞因子水平均显著降低（P< 0.05）。在没有ME 1071的情况下，比阿培南在血浆中高于MIC（%T> MIC）的时间百分比为0%;然而，在使用ME 1071的情况下，该值升高至10.8%。这些结果表明，ME 1071对由MBL产生P引起的VAP是有效的和有效的。铜绿。
ME1071, a maleic acid derivative, is a novel, specific inhibitor of metallo-β-lactamases (MBLs). In vitro, ME1071 can potentiate the activity of carbapenems against MBL-producing Pseudomonas aeruginosa. To confirm the clinical efficacy of ME1071 in ventilator-associated pneumonia (VAP) caused by MBL-producingP. aeruginosa, a mouse model that mimics VAP by placement of a plastic tube in the bronchus was used. Biapenem (100 mg/kg) or ME1071 plus biapenem (each 100 mg/kg) was administered intraperitoneally every 12 h beginning at 12 h after inoculation. Survival was evaluated over 7 days. At 30 h post infection, mice were sacrificed and the numbers of viable bacteria in the lungs and bronchoalveolar lavage fluid (BALF) were compared. Histopathological analysis of lung specimens was also performed. The pharmacokinetics of ME1071 was analysed after initial treatment. The ME1071 plus biapenem combination group displayed significantly longer survival compared with the control and biapenem monotherapy groups (P< 0.05). Furthermore, the number of viable bacteria in the lungs was significantly lower in the combination group (P< 0.05). Histopathological examination of lung specimens indicated that progression of lung inflammation was prevented in the combination group. Furthermore, total cell and neutrophil counts, as well as cytokine levels, in BALF were significantly decreased (P< 0.05) in the combination group. The percentage time above the MIC (%T> MIC) for biapenem without ME1071 was 0% in plasma; however, this value was elevated to 10.8% with ME1071. These results suggest that ME1071 is potent and effective for treatment of VAP caused by MBL-producingP. aeruginosa.
脂多糖诱导小鼠肺粘液细胞化生。
DOI：
10.1165/ajrcmb.24.1.4122
发表时间：
2001
期刊：
American journal of respiratory cell and molecular biology.
影响因子：
--
作者：
Yanagihara,K;Seki,M;Cheng,PW
通讯作者：
Cheng,PW