硫酸依替米星体外抗菌活性研究

In vitro activity of etimicin sulfate

目的评价硫酸依替米星对近年临床常见分离菌的体外抗菌活性及防突变浓度(MPC)。方法最低抑菌浓度(MIC)用标准琼脂二倍稀释法测定,MPC用涂菌计数法测定。结果对2015年至2017年全国范围内临床分离1035株细菌进行MIC测定。结果显示:硫酸依替米星对葡萄球菌具有较好抗菌活性,对甲氧西林耐药葡萄球菌的MIC50值(0.125~1 mg·L^(-1))与甲氧西林敏感菌(0.25~0.5 mg·L^(-1))基本一致,表明其对甲氧西林耐药葡萄球菌具有一定抗菌作用。此外,对于革兰氏阳性菌中的化脓性链球菌、草绿色链球菌及革兰氏阴性菌中超广谱β-内酰胺酶(ESBLs)阴性大肠埃希菌、ESBLs阴性肺炎克雷伯菌、肠杆菌属、沙门菌属、志贺菌属、亚胺培南敏感鲍曼不动杆菌、流感嗜血杆菌和卡他莫拉菌,硫酸依替米星也具有较好抗菌作用,与庆大霉素、奈替米星相似,对革兰氏阳性菌优于阿米卡星和异帕米星。对于大肠埃希菌和铜绿假单胞菌,硫酸依替米星的MPC值多为MIC值的4~8倍,略优于阿米卡星,优于左氧氟沙星和米诺环素。但对于金黄色葡萄球菌和鲍曼不动杆菌,MPC/MIC比值多≥8,耐药选择窗(MSW)较宽。结论硫酸依替米星对葡萄球菌、部分链球菌、大部分革兰氏阴性菌仍保持较好抗菌活性,且对于大肠埃希菌和铜绿假单胞菌MSW较窄,不易筛选出耐药菌株。对于MSW较宽的菌种,可采取保持较高药物浓度或联合用药的方式以防耐药突变株产生。

Objective To evaluation in vitro activity and mutant prevention concentration（ MPC） of etimicin sulfate against main clinical isolated strains. Methods Minimal inhibition concentrations（ MIC） were tested by agar dilution method and MPC were measured by smear bacteria and colony form unit（ CFU） count method. Results All of 1035 stains isolated from 2015 to 2017 across the country were studied. Etimicin sulfate showed good antibacterial activity against Staphylococcus and MIC50 values from 0. 125^（-1） mg·L^（-1） regardless the isolates methicillin resistance or not,indicating that etimicin sulfate has potency against part of methicilun-resistact Staphylococcus aureus. Etimicin sulfate also exhibited good antibacterial activity against Streptococcus pyogenes,Streptococcus viridans,extended spectrum beta-lactamases（ ESBLs） negative Escherichia coli and Klebsiella pneumoniae,Enterobacter,Salmonella,Shigella,imipenem-susceptible Acinetobacter baumanii,Haemophilus influenzae and Moraxella catarrhalis,compared to gentamicin and netilmicin,better than amikacin and isepamicin for gram-positive cocci. MPC values of etimicin sulfate were 4-8 times higher than MICs forEscherichia coli and Pseudomonas aeruginosa. The ratios of MPC/MIC of etimicin sulfate were better than amikacin,levofloxacin and minocycline. For Staphylococcus aureus and Acinetobacter baumanii,the ratios of MPC/MIC were most≥8 times that meant mutation selection window（ MSW） of etimicin sulfate were broader. Conclusion Etimicin sulfate still demonstrate well antibacterial activity against Staphylococcus aureus and part Streptococcus,gram-negative strains. MSW were narrow for Escherichia coli and Pseudomonas aeruginosa,implying that resistance strains were not been selected easy. For strains that MSW were wide,maintaining a high drug concentration or antimicrobial combination may be effective to prevent resistant mutants.