New In Vitro Model To Study the Effect of Human Simulated Antibiotic Concentrations on Bacterial Biofilms
New In Vitro Model To Study the Effect of Human Simulated Antibiotic Concentrations on Bacterial Biofilms
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DOI：
10.1128/aac.05037-14
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发表时间：
2015-07-01
影响因子：
4.9
通讯作者：
Yang, Katherine
中科院分区：
文献类型：
--
作者：
Haagensen, Janus A. J.;Verotta, Davide;Yang, Katherine
介绍了一种利用流动池技术和激光共聚焦扫描显微镜技术进行细菌生物膜体外药代动力学/药效学模拟的新方法。该装置能够模拟与在连续培养条件下生长的细菌生物膜上静脉给药相关的人体内抗生素浓度变化。模拟了2 g美罗培南单次静脉推注给药的游离药物浓度和半衰期为0.895 h的一级消除（消除速率常数为0.776 h（-1））。研究美罗培南对铜绿假单胞菌PAO 1和3株临床分离自囊性纤维化患者的铜绿假单胞菌生物被膜的抗菌活性。此外，美罗培南对培养24 h的PAO 1生物膜的影响与对培养72 h的生物膜的影响进行了检查。使用共聚焦激光扫描显微镜，在给药间隔的第一个小时内观察到所有生物膜的快速生物膜杀灭。然而，对于培养72小时的PAO 1生物膜，仅生物膜外围的细菌亚群受到影响，即使在给药间隔结束时，基质的亚群仍保持活力。所描述的模型是一种新的方法来研究使用人体模拟浓度的细菌生物膜的抗菌剂杀灭。
A new in vitro pharmacokinetic/pharmacodynamic simulator for bacterial biofilms utilizing flow cell technology and confocal laser scanning microscopy is described. The device has the ability to simulate the changing antibiotic concentrations in humans associated with intravenous dosing on bacterial biofilms grown under continuous culture conditions. The free drug concentrations of a single 2-g meropenem intravenous bolus dose and first-order elimination utilizing a half-life of 0.895 h (elimination rate constant, 0.776 h(-1)) were simulated. The antibacterial activity of meropenem against biofilms of Pseudomonas aeruginosa PAO1 and three clinical strains isolated from patients with cystic fibrosis was investigated. Additionally, the effect of meropenem on PAO1 biofilms cultured for 24 h versus that on biofilms cultured for 72 h was examined. Using confocal laser scanning microscopy, rapid biofilm killing was observed in the first hour of the dosing interval for all biofilms. However, for PAO1 biofilms cultured for 72 h, only bacterial subpopulations at the periphery of the biofilm were affected, with subpopulations at the substratum remaining viable, even at the conclusion of the dosing interval. The described model is a novel method to investigate antimicrobial killing of bacterial biofilms using human simulated concentrations.