Pomegranate pericarp extract enhances the antibacterial activity of ciprofloxacin against extended-spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) producing Gram-negative bacilli
Pomegranate pericarp extract enhances the antibacterial activity of ciprofloxacin against extended-spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) producing Gram-negative bacilli
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DOI：
10.1016/j.fct.2012.09.001
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发表时间：
2012-12-01
影响因子：
4.3
通讯作者：
Hazra, Banasri
中科院分区：
文献类型：
--
作者：
Dey, Diganta;Debnath, Sukalyani;Hazra, Banasri
采用石榴果皮乙醇提取物(PGME)与环丙沙星联合应用，对产超广谱β-内酰胺酶(ESBL)的大肠埃希菌、肺炎克雷伯菌和产金属β-内酰胺酶(MBL)的铜绿假单胞菌进行联合药敏试验，筛选其对氟喹诺酮类抗生素的耐药性。测定环丙沙星和PGME的最低抑菌浓度(MIC)，并用棋盘法和分数抑菌浓度(FIC)法评价环丙沙星与PGME的协同作用。琼脂扩散法进一步证实19株菌株与环丙沙星有协同作用(对环丙沙星的FIC值为0.125~0.50)。这可能是由于PGME的多酚成分具有细菌外排泵抑制物(EPI)活性。然而，对环丙沙星耐药水平较高的菌株对环丙沙星-PGME组合没有反应，这可能是由于靶位修饰不受PGME的EPI活性的进一步影响。同样，一些菌株对环丙沙星敏感或抗药性较弱，对环丙沙星表现出“冷漠”，可能是因为缺乏过度表达的外排机制。因此，环丙沙星-PGME组合首次证明了对产生ESBL和MBL的革兰氏阴性杆菌的协同作用，并在一种廉价替代疗法的帮助下提高了现有药物的疗效。(C)2012爱思唯尔有限公司。保留所有权利。
A methanolic extract of Punica granatum (pomegranate) fruit pericarp (PGME) was tested in combination with ciprofloxacin against extended-spectrum beta-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae, and metallo-beta-lactamase (MBL) producing Pseudomonas aeruginosa, which were screened for their resistance profile against fluoroquinolone antibiotics. The minimum inhibitory concentrations (MIC) of ciprofloxacin and PGME, alone, were determined, and synergy of ciprofloxacin-PGME combinations evaluated by checkerboard assay and fractional inhibitory concentration (FIC). Nineteen out of forty-nine strains exhibited synergy with ciprofloxacin (FIC of 0.125-0.5 for ciprofloxacin) further verified by agar-well assay. This could be due to the bacterial efflux pump inhibitor (EPI) activity of the polyphenolic constituents of PGME. However, the isolates exhibiting a high level of ciprofloxacin resistance did not respond to ciprofloxacin-PGME combinations, which could be due to target site modification not influenced further by EPI activity of PGME. Again, some strains were sensitive or weakly resistant to ciprofloxacin, which exhibited 'indifference' to the combination, probably due to a lack of over-expressed efflux mechanism. Thus, a synergy of a ciprofloxacin-PGME combination was demonstrated for the first time against ESBL- and MBL-producing Gram-negative bacilli, and the efficacy of an existing drug improved with the help of an inexpensive alternative therapy. (C) 2012 Elsevier Ltd. All rights reserved.