Cottagnoud P, Cottagnoud M, Täuber M G
Department of Internal Medicine, Inselspital Bern, Bern, Switzerland.
Antimicrob Agents Chemother. 2003 Jan;47(1):144-7. doi: 10.1128/AAC.47.1.144-147.2003.
Vancomycin and gentamicin act synergistically against penicillin-resistant pneumococci in vitro and in experimental rabbit meningitis. The aim of the present study was to investigate the underlying mechanism of this synergism. The intracellular concentration of gentamicin was measured by using the following experimental setting. Bacterial cultures were incubated with either gentamicin alone or gentamicin plus vancomycin for a short period (15 min). The gentamicin concentration was determined before and after grinding of the cultures by using the COBAS INTEGRA fluorescence polarization system (Roche). The grinding efficacies ranged between 44 and 54%, as determined by viable cell counts. In the combination regimen the intracellular concentration of gentamicin increased to 186% compared to that achieved with gentamicin monotherapy. These data suggest that the synergy observed in vivo and in vitro is based on an increased intracellular penetration of the aminoglycoside, probably due to the effect of vancomycin on the permeability of the cell wall.
万古霉素和庆大霉素在体外以及实验性兔脑膜炎模型中对耐青霉素肺炎球菌具有协同作用。本研究的目的是探究这种协同作用的潜在机制。通过以下实验设置来测量庆大霉素的细胞内浓度。将细菌培养物分别与单独的庆大霉素或庆大霉素加万古霉素孵育短时间（15分钟）。使用COBAS INTEGRA荧光偏振系统（罗氏公司）在研磨培养物前后测定庆大霉素浓度。通过活菌计数确定研磨效率在44%至54%之间。在联合用药方案中，庆大霉素的细胞内浓度相比于庆大霉素单药治疗增加到了186%。这些数据表明，体内和体外观察到的协同作用是基于氨基糖苷类药物细胞内渗透增加，这可能是由于万古霉素对细胞壁通透性的影响。
