多黏菌素异质性耐药的研究进展及临床意义

Research progress and clinical significance of polymyxin heteroresistance

由于抗菌药物的大量使用,细菌的耐药性不断产生。如今,多黏菌素已成为抗多重耐药菌,尤其是碳青霉烯类耐药革兰阴性菌感染的最后一道防线药物。然而近几年来关于多黏菌素耐药的报道不断增加,并且已有研究发现多黏菌素的异质性耐药现象。异质性耐药是细菌由敏感到耐药的中间过程,常规的临床检验无法有效检测出异质性耐药,这对临床治疗用药造成了巨大的威胁,造成患者的反复感染和用药失败。但对其机制的研究较少,目前发现的主要与染色体上脂多糖(LPS)相关基因的突变,耐药基因的不稳定扩增和外排泵系统有关。本文总结了细菌异质性耐药,尤其是多黏菌素异质性耐药的研究及其临床意义。

Due to the extensive use of antibiotics, bacterial resistance is constantly emerging. Nowadays, polymyxins have become the last-resort to defend against multidrug-resistant bacteria, especially carbapenem-resistant Gram-negative bacteria. However, in recent years, there are more and more reports about polymyxin resistance, and the heteroresistance of polymyxins has been found to be a severe situation. Heteroresistance is the intermediate process from sensitivity to drug resistance. Routine clinical tests cannot effectively detect the heteroresistance, which poses a huge threat to the clinical treatment of drugs, resulting in repeated infections and drug failure. However, there are few researches on its mechanism. At present, it is mainly related to the mutations of LPS related genes on chromosomes, the unstable amplification of drug-resistant genes, and the efflux pump system. In this paper, we summarize the related research of bacterial heteroresistance, especially heteroresistance of polymyxins and its clinical significance.