磷霉素联合疗法对耐黏菌素菌的体外抗菌作用
In vitro antibacterial effect of fosfomycin combination therapy against colistin-resistant .
作者信息
Yu Wei, Luo Qixia, Shi Qingyi, Huang Chen, Yu Xiao, Niu Tianshui, Zhou Kai, Zhang Jiajie, Xiao Yonghong
机构信息
State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
Department of Infectious Diseases, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, People's Republic of China.
出版信息
Infect Drug Resist. 2018 Apr 24;11:577-585. doi: 10.2147/IDR.S160474. eCollection 2018.
OBJECTIVES
Colistin is still a "last-resort" antibiotic used to manage human infections due to multidrug-resistant (MDR) . However, colistin-resistant (CR-Kp) isolates emerged a decade ago and had a worldwide distribution. The purpose of this study was to evaluate the genetic data of CR-Kp and identify the antibacterial activity of fosfomycin (FM) alone and in combination with amikacin (AMK) or colistin (COL) against CR-Kp in vitro.
METHODS
Three clinical CR-Kp isolates from three patients were collected. Whole-genome sequencing and bioinformatics analysis were performed. The Pharmacokinetics Auto Simulation System 400, by simulating human pharmacokinetics in vitro, was employed to simulate FM, AMK, and COL alone and in combination. Different pharmacodynamic parameters were calculated for determining the antimicrobial effect.
RESULTS
Whole-genome sequencing revealed that none of the three isolates contain gene and that no insertion was found in , , or genes. We found the antibacterial activity of AMK alone was more efficient than FM or COL against CR-Kp. The area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was higher than 170 LogCFU/mL·h. In addition, the area between the control growth and antibacterial killing curves of FM (8 g every 8 hours) combined with COL (75,000 IU/kg every12 hours) was higher than that of monotherapies (>100 LogCFU/mL·h vs <80 LogCFU/mL·h).
CONCLUSION
FM (8 g every 8 hours) combined with AMK (15 mg/kg once daily) was effective at maximizing bacterial killing against CR-Kp.
目的
黏菌素仍是用于治疗多重耐药菌所致人类感染的“最后手段”抗生素。然而，耐黏菌素肺炎克雷伯菌（CR-Kp）分离株在十年前出现并在全球范围内传播。本研究的目的是评估CR-Kp的基因数据，并确定磷霉素（FM）单独以及与阿米卡星（AMK）或黏菌素（COL）联合使用对CR-Kp的体外抗菌活性。
方法
收集了来自三名患者的三株临床CR-Kp分离株。进行了全基因组测序和生物信息学分析。使用药物动力学自动模拟系统400，通过体外模拟人体药代动力学，来模拟FM、AMK和COL单独及联合使用的情况。计算不同的药效学参数以确定抗菌效果。
结果
全基因组测序显示，三株分离株均不含有 基因，且在 、 或 基因中未发现插入情况。我们发现，AMK单独使用对CR-Kp的抗菌活性比FM或COL更高。FM（每8小时8克）联合AMK（每日一次，15毫克/千克）的对照生长曲线与抗菌杀灭曲线之间的面积高于170 LogCFU/mL·h。此外，FM（每8小时8克）联合COL（每12小时75,000 IU/千克）的对照生长曲线与抗菌杀灭曲线之间的面积高于单一疗法（>100 LogCFU/mL·h对<80 LogCFU/mL·h）。
结论
FM（每8小时8克）联合AMK（每日一次，15毫克/千克）能有效最大化对CR-Kp的细菌杀灭效果。
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