Antimicrobial Activity and Toxicity of the Major Lipopeptide Components of Polymyxin B and Colistin: Last-line Antibiotics against Multidrug-Resistant Gram-negative Bacteria.
Antimicrobial Activity and Toxicity of the Major Lipopeptide Components of Polymyxin B and Colistin: Last-line Antibiotics against Multidrug-Resistant Gram-negative Bacteria.
复制标题
多粘蛋白B和colistin的主要脂肽成分的抗菌活性和毒性：针对多药耐药的革兰氏阴性细菌的最后一线抗生素。
DOI：
10.1021/acsinfecdis.5b00085
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发表时间：
2015-11-13
影响因子：
5.3
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Roberts KD;Azad MA;Wang J;Horne AS;Thompson PE;Nation RL;Velkov T;Li J
多粘菌素B和粘菌素目前被用作耐多药革兰氏阴性菌的“最后一线”治疗方法。然而，对于多粘菌素B1、多粘菌素B2、粘菌素A、粘菌素B这些多粘菌素B和粘菌素产品中主要的环状脂肽成分之间的药理差异了解甚少。在这里，我们报道了这些主要脂肽成分的体外和体内抗菌活性和毒性。所有四种脂肽与一组临床革兰氏阴性分离株的mic值相当（< 0.125-4 mg/L）。在小鼠模型中，它们也具有相当的体内抗菌活性（Δlog10 CFU/mL >-3）和肾毒性（轻度至中度组织学损伤）。然而，多粘菌素B1和粘菌素A对人肾近端小管HK-2细胞的体外凋亡作用分别明显高于多粘菌素B2和粘菌素B（3倍）。与商业多粘菌素和粘菌素产品相比，单个脂肽成分具有稍高的体内抗菌活性。我们的研究结果强调有必要重新评估多粘菌素B和粘菌素的药典标准，并规范多粘菌素抗生素不同商业产品的组成。
Polymyxin B and colistin are currently used as a ‘last-line’ treatment for multidrug-resistant Gram-negative bacteria. However very little is known about the pharmacological differences between polymyxin B1, polymyxin B2, colistin A, colistin B, the major cyclic lipopeptides components present in polymyxin B and colistin products. Here, we report on the in vitro and in vivo antimicrobial activity and toxicity of these major lipopeptide components. All four lipopeptides had comparable MICs (<0.125–4 mg/L) against a panel of clinical Gram-negative isolates. They also had comparable in vivo antimicrobial activity (Δlog10 CFU/mL >-3) and nephrotoxicity (mild to moderate histological damage) in mouse models. However, polymyxin B1 and colistin A showed significantly higher (> 3-fold) in vitro apoptotic effect on human kidney proximal tubular HK-2 cells than polymyxin B2 and colistin B, respectively. Compared to the commercial polymyxin and colistin products, the individual lipopeptide components had slightly more in vivo antimicrobial activity. Our results highlight the need to re-assess pharmacopoeial standards for polymyxins B and colistin and to standardize the composition of the different commercial products of polymyxin antibiotics.