•
1624 •中华中医药杂志(原中国医药学报) 2012年6月第27卷第6期 CJTCMP , June 2012,Vol . 27, No. 6
・综述・
中药抗肺炎克雷伯菌及逆转耐药性的研究进展
钟海琴1，蔡挺2，张顺3
（1宁波大学医学院，宁波 315211；2宁波市第二医院急诊科，宁波 315010；3宁波市第二医院
临床研究室，宁波 315010）
摘要：肺炎克雷伯菌已成为院内感染的重要病原菌，且多重耐药菌株不断出现，已经成为临床治疗感染的一大难题。中药凭借自身优点受到广泛关注，其多重抗菌活性为解决病原菌的多重耐药提供了新的思路。文章介绍了肺炎克雷伯菌多重耐药机制、传播机制和具有抗菌作用的中药，从消除耐药质粒、抑制灭活酶和主动外排方面阐述了抗菌中药逆转菌株耐药性的作用，并探讨抗菌中药研究中存在的一些问题，以期为临床用药和抗菌药物的研发提供参考。
关键词：肺炎克雷伯菌；多重耐药；中药
Development of traditional Chinese medicine in inhibiting klebsiella pneumoniae and
reversing its drug resistance
ZHONG Hai-qin1, CAI Ting2, ZHANG Shun3
( 1School of Medicine, Ningbo University, Ningbo 315211, China; 2Department of Emergency, Ningbo No.2 Hospital, Ningbo
315010, China; 3Clinical Laboratory, Ningbo No.2 Hospital, Ningbo 315010, China )
Abstract: Klebsiella pneumoniae has become the important pathogens of nosocomial infection. Broad-spectrum
antibacterial consumption is increasing clinically in many countries around the world, and it is increasingly recognized as the major reason for the emergence of resistance. The recent alarming rise of infections caused by antibiotic-resist pathogens, including multidrug resistant klebsiella pneumoniae, has been observed, particularly in intensive care units. Traditional Chinese medicine (TCM) becomes a subject of concern with low resistance and low toxic side effects of the signifi cant advantages. They proved to be active against the Gram-positive and Gram-negative organisms. There is also evidence show that the resistance of K. pneumoniae isolates could be moderately reversed by using TCM to inhibit resistant plasmid, inactived enzyme and active ef fl ux pump. Besides, the combinations of antibiotics and Chinese medicines exhibit active effects. Focusing on the molecular mechanism of bacterial resistance, this paper reviewed the progress in the studies of inhibitor of traditional Chinese medicine to K. pneumoniae in recent years, in order to provide a new approach to clinical medication and new drug research.
Key words: Klebsiella pneumoniae; Multidrug resistance; Traditional Chinese medicine
近年来肺炎克雷伯菌（klebsiella pneumoniae，KPN ）已成为院内感染的重要病原菌。KPN对β-内酰胺类和氨基糖苷类等抗生素出现了严重的多重耐药，临床治疗困难，常引起致死性感染。中药的成分复杂，杀菌机制多，不易产生耐药性，在感染治疗中有明显效果。寻找具有抗菌活性的中草药成分，利用其多重抗菌活性解决令人棘手的耐药菌感染以及限制多重耐药性的产生和扩散无疑是一条可以尝试的途径。
肺炎克雷伯菌的多重耐药机制1. 产生灭活酶
1.1β-内酰胺酶 目前KPN常产生β-内酰胺酶水解青霉素或头孢菌素等抗生素中的β-内酰胺环从而使抗生素失去抗菌活性。β-内酰胺酶包括超广谱β-内酰胺酶（extended
spectrum β-lactamases，ESBLs ）、头孢菌素酶（ambler class Cβ-lactamase，AmpC酶）、肺炎克雷伯菌碳青霉烯酶（klebsiella pneumoniae carbapenemase，KPC酶）及金属酶等，其中KPC酶和金属酶甚至导致泛耐药KPN的出现。
1.2 氨基糖苷修饰酶 产生氨基糖苷修饰酶是KPN对氨基糖苷类抗生素耐药的主要机制。该酶修饰抗菌药物分子中具有抗菌活性的基团，使其与作用靶位核糖体的亲和力大大降低从而导致耐药的产生。氨基糖苷修饰酶包括N-乙酰转移酶、腺苷转移酶、磷酸转移酶等。
2. 抗菌药物渗透障碍
2.1 外膜孔蛋白的改变 革兰氏阴性菌细胞外膜上有许多由孔蛋白组成的抗菌药物渗透孔道。若孔蛋白改变或缺失，则
通讯作者：蔡挺，浙江省宁波市西北街41号宁波市第二医院急诊科，邮编：315010，电话（传真）：0574-83870901，E-mail：[email protected]
•
1624 •中华中医药杂志(原中国医药学报) 2012年6月第27卷第6期 CJTCMP , June 2012,Vol . 27, No. 6
・综述・
中药抗肺炎克雷伯菌及逆转耐药性的研究进展
钟海琴1，蔡挺2，张顺3
（1宁波大学医学院，宁波 315211；2宁波市第二医院急诊科，宁波 315010；3宁波市第二医院
临床研究室，宁波 315010）
摘要：肺炎克雷伯菌已成为院内感染的重要病原菌，且多重耐药菌株不断出现，已经成为临床治疗感染的一大难题。中药凭借自身优点受到广泛关注，其多重抗菌活性为解决病原菌的多重耐药提供了新的思路。文章介绍了肺炎克雷伯菌多重耐药机制、传播机制和具有抗菌作用的中药，从消除耐药质粒、抑制灭活酶和主动外排方面阐述了抗菌中药逆转菌株耐药性的作用，并探讨抗菌中药研究中存在的一些问题，以期为临床用药和抗菌药物的研发提供参考。
关键词：肺炎克雷伯菌；多重耐药；中药
Development of traditional Chinese medicine in inhibiting klebsiella pneumoniae and
reversing its drug resistance
ZHONG Hai-qin1, CAI Ting2, ZHANG Shun3
( 1School of Medicine, Ningbo University, Ningbo 315211, China; 2Department of Emergency, Ningbo No.2 Hospital, Ningbo
315010, China; 3Clinical Laboratory, Ningbo No.2 Hospital, Ningbo 315010, China )
Abstract: Klebsiella pneumoniae has become the important pathogens of nosocomial infection. Broad-spectrum
antibacterial consumption is increasing clinically in many countries around the world, and it is increasingly recognized as the major reason for the emergence of resistance. The recent alarming rise of infections caused by antibiotic-resist pathogens, including multidrug resistant klebsiella pneumoniae, has been observed, particularly in intensive care units. Traditional Chinese medicine (TCM) becomes a subject of concern with low resistance and low toxic side effects of the signifi cant advantages. They proved to be active against the Gram-positive and Gram-negative organisms. There is also evidence show that the resistance of K. pneumoniae isolates could be moderately reversed by using TCM to inhibit resistant plasmid, inactived enzyme and active ef fl ux pump. Besides, the combinations of antibiotics and Chinese medicines exhibit active effects. Focusing on the molecular mechanism of bacterial resistance, this paper reviewed the progress in the studies of inhibitor of traditional Chinese medicine to K. pneumoniae in recent years, in order to provide a new approach to clinical medication and new drug research.
Key words: Klebsiella pneumoniae; Multidrug resistance; Traditional Chinese medicine
近年来肺炎克雷伯菌（klebsiella pneumoniae，KPN ）已成为院内感染的重要病原菌。KPN对β-内酰胺类和氨基糖苷类等抗生素出现了严重的多重耐药，临床治疗困难，常引起致死性感染。中药的成分复杂，杀菌机制多，不易产生耐药性，在感染治疗中有明显效果。寻找具有抗菌活性的中草药成分，利用其多重抗菌活性解决令人棘手的耐药菌感染以及限制多重耐药性的产生和扩散无疑是一条可以尝试的途径。
肺炎克雷伯菌的多重耐药机制1. 产生灭活酶
1.1β-内酰胺酶 目前KPN常产生β-内酰胺酶水解青霉素或头孢菌素等抗生素中的β-内酰胺环从而使抗生素失去抗菌活性。β-内酰胺酶包括超广谱β-内酰胺酶（extended
spectrum β-lactamases，ESBLs ）、头孢菌素酶（ambler class Cβ-lactamase，AmpC酶）、肺炎克雷伯菌碳青霉烯酶（klebsiella pneumoniae carbapenemase，KPC酶）及金属酶等，其中KPC酶和金属酶甚至导致泛耐药KPN的出现。
1.2 氨基糖苷修饰酶 产生氨基糖苷修饰酶是KPN对氨基糖苷类抗生素耐药的主要机制。该酶修饰抗菌药物分子中具有抗菌活性的基团，使其与作用靶位核糖体的亲和力大大降低从而导致耐药的产生。氨基糖苷修饰酶包括N-乙酰转移酶、腺苷转移酶、磷酸转移酶等。
2. 抗菌药物渗透障碍
2.1 外膜孔蛋白的改变 革兰氏阴性菌细胞外膜上有许多由孔蛋白组成的抗菌药物渗透孔道。若孔蛋白改变或缺失，则
通讯作者：蔡挺，浙江省宁波市西北街41号宁波市第二医院急诊科，邮编：315010，电话（传真）：0574-83870901，E-mail：[email protected]