Colistin Sulfate is a structurally distinct class of nonribosomal, cyclic oligopeptides antimicrobials. Colistin Sulfate is mainly active against multidrug-resistant Gram-negative bacteria (GNB), exerting its antibacterial effect by directly interacting with the lipid A component of lipopolysaccharide (LPS) in the outer membrane (OM). The mainstream mechanism is: The cationic diaminobutyric acid (Dab) residues of Colistin Sulfate electrostatically bind to the anionic phosphate groups of lipid A, competitively displacing divalent cations (such as Mg²⁺ and Ca²⁺) from the membrane. This interaction disrupts the outer membrane, increases its permeability, leads to leakage of intracellular contents, and ultimately results in bacterial cell death[1].
In vitro, different Klebsiella pneumoniae isolates show variable susceptibility to Colistin Sulfate, with susceptible strains having Minimum Inhibitory Concentration (MIC) of 0.125-1mg/L and resistant strains exhibiting MIC of 32–128mg/L. Colistin Sulfate exerts rapid bactericidal activity against Klebsiella pneumoniae within 1 hour, but substantial regrowth may subsequently occur[2]. Colistin Sulfate has an MIC of 2μg/mL against the Ab396 strain of carbapenem-resistant Acinetobacter baumannii (CRAB)[3].
In vivo, Colistin Sulfate (75000U/kg; i.t.), administered every 8 hours for a total of 48 hours, significantly reduced lung bacterial loads and normalized the lung wet weight/body weight ratio in acute pneumonia mice inoculated with 2.5×10⁷ CFU (Colony Forming Unit) of Ab396 and 10% porcine mucin. Colistin Sulfate (75000U/kg; i.t.) showed superior efficacy compared to colistin Sulfate (150000U/kg; i.p.)[3].
References:
[1] El-Sayed Ahmed, Mohamed Abd El-Gawad et al. “Colistin and its role in the Era of antibiotic resistance: an extended review (2000-2019).” Emerging microbes & infections vol. 9,1 (2020): 868-885.
[2] Poudyal, Anima et al. “In vitro pharmacodynamics of colistin against multidrug-resistant Klebsiella pneumoniae.” The Journal of antimicrobial chemotherapy vol. 62,6 (2008): 1311-8.
[3] Chiang, Shyh-Ren et al. “Intratracheal colistin sulfate for BALB/c mice with early pneumonia caused by carbapenem-resistant Acinetobacter baumannii.” Critical care medicine vol. 37,9 (2009): 2590-5.
Colistin Sulfate是一种结构独特的非核糖体环状寡肽抗菌剂。Colistin Sulfate主要作用于耐多药革兰氏阴性菌（GNB），它通过与外膜脂多糖（LPS）的脂质A组分直接相互作用来发挥其抗菌作用。主流机制认为Colistin Sulfate中的阳离子二氨基丁酸（Dab）残基可与脂质A的阴离子磷酸基团发生静电结合，竞争性地取代膜上的二价阳离子（如Mg²⁺和Ca²⁺），从而破坏细菌外膜结构并增加其通透性，导致细胞内物质泄漏，最终引起细菌死亡[1]。
体外实验中，不同的肺炎克雷伯菌（Klebsiella pneumoniae）分离株对Colistin Sulfate的敏感性存在差异，其中敏感株的最小抑菌浓度（MIC）为0.125-1mg/L，而耐药株的MIC为32-128mg/L。Colistin Sulfate在1小时内对肺炎克雷伯菌具有快速的杀菌活性，但随后可能发生大量的再生[2]。Colistin Sulfate对耐碳青霉烯类鲍曼不动杆菌（Acinetobacter baumannii; CRAB）Ab396菌株的MIC为2μg/mL[3]。
体内实验中，Colistin Sulfate（75000U/kg；i.t.），每8小时给药一次，共持续48小时，可显著降低接种了2.5×107菌落形成单位（CFU）的Ab396菌株及10%猪黏蛋白的急性肺炎小鼠肺部细菌负荷，并使肺湿重/体重比恢复至正常水平。Colistin sulfate（75000U/kg; i.t.）的给药效果优于Colistin sulfate（150000U/kg; i.p.）[3]。