Investigation of the antimicrobial effects of linezolid on bacterial biofilms utilizing an in vitro pharmacokinetic model
Investigation of the antimicrobial effects of linezolid on bacterial biofilms utilizing an in vitro pharmacokinetic model
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DOI：
10.1093/jac/49.2.301
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发表时间：
2002-02-01
影响因子：
5.2
通讯作者：
Finch, R
中科院分区：
文献类型：
--
作者：
Gander, S;Hayward, K;Finch, R
甲氧西林敏感和耐药金黄色葡萄球菌、凝固酶阴性葡萄球菌和糖肽中间型葡萄球菌的生物被膜。金黄色葡萄球菌（GISA）暴露于恶唑烷酮利奈唑胺和四种对照抗生素（奎奴普汀/达福普汀、万古霉素、替考拉宁和环丙沙星）。通过监测从生物膜洗脱的细胞数量的减少来评估这些抗生素的作用。通过两种方法将生物膜暴露于抗生素。第一种是药物浓度指数递减法，稀释率与抗生素的半衰期相匹配，初始浓度与血清峰值水平相匹配。第二种是恒定药物浓度方法，其中生物膜暴露于抗生素2小时，抗生素的浓度等于指数递减方法中使用的药物总量。结果表明，除一种GISA菌株Mu 50外，与恒定浓度暴露相比，利奈唑胺使采用指数递减法洗脱的细胞数量减少更大。总体而言，环丙沙星在指数递减浓度实验中产生最大的效果，但仅针对非耐药菌株。在恒定浓度暴露中，没有一种药物导致观察到的细胞数量的最大减少。利奈唑胺和奎奴普汀/达福普汀使两种暴露方法中检测的所有菌株的生物膜洗脱的细胞数量减少，应考虑用于治疗葡萄球菌生物膜相关感染的进一步临床研究。
Biofilms of methicillin-susceptible and -resistant Staphylococcus aureus, a strain of coagulase-negative staphylococcus and glycopeptide-intermediate strains of S. aureus (GISA) were exposed to the oxazolidinone linezolid, and four comparator antibiotics (quinupristin/dalfopristin, vancomycin, teicoplanin and ciprofloxacin) using a Sorbarod model. The effects of these antibiotics were assessed by monitoring the reduction in the number of cells eluted from the biofilms. The biofilms were exposed to the antibiotics by two methods. The first was an exponentially decreasing drug concentration method, where the rate of dilution was matched to the half-lives of the antibiotics and the initial concentration matched peak serum levels. The second was a constant drug concentration method, in which biofilms were exposed to antibiotics for 2 h, with the concentration of the antibiotic equalling the total amount of drug used in the exponentially decreasing method. The results indicate that linezolid produces a greater reduction in the number of cells eluted with the exponentially decreasing method compared with the constant concentration exposure against all strains tested except for one of the GISA strains, Mu 50. Overall, ciprofloxacin produced the greatest effects in the exponentially decreasing concentration experiments, but only against non-resistant strains. In the constant concentration exposure no one drug was responsible for the largest reductions in cell numbers observed. Linezolid and quinupristin/dalfopristin produced a reduction in the number of cells eluted from the biofilms of all of the strains tested in both methods of exposure and should be considered for further clinical studies of the treatment of staphylococcal biofilm-associated infections.