痰热清注射液与头孢他啶联用对铜绿假单胞菌的体外耐药敏化作用研究
Study on drug-resistance sensitization effect of Tanreqing Injection combined with ceftazidime on pseudomonas aeruginosa
in vitro - 北京中医药 2023年42卷第8期 页码：824-830
- 作者机构：
1.中国中医科学院医学实验中心，北京 100700
2.中国中医科学院望京医院呼吸科，北京 100102
- 作者简介：
李露，女，31岁，博士研究生。研究方向：中医药抗菌机制研究。
王毅，E-mail：Prof.wangyi@foxmail.com
- 基金信息：中国中医科学院科技创新工程重大攻关项目(CI2021A00601);中国中医科学院优秀青年科技人才培养专项(ZZ16-YQ-037)
DOI：10.16025/j.1674-1307.2023.08.003
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李露，刘爽，崔开宇，等.痰热清注射液与头孢他啶联用对铜绿假单胞菌的体外耐药敏化作用研究［J］.北京中医药，2023，42（8）：824-830.
LI Lu,LIU Shuang,CUI Kai-yu,et al.Study on drug-resistance sensitization effect of Tanreqing Injection combined with ceftazidime on pseudomonas aeruginosa in vitro[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(08):824-830.
李露，刘爽，崔开宇，等.痰热清注射液与头孢他啶联用对铜绿假单胞菌的体外耐药敏化作用研究［J］.北京中医药，2023，42（8）：824-830. DOI： 10.16025/j.1674-1307.2023.08.003.
LI Lu,LIU Shuang,CUI Kai-yu,et al.Study on drug-resistance sensitization effect of Tanreqing Injection combined with ceftazidime on pseudomonas aeruginosa in vitro[J]. Beijing Journal of Traditional Chinese Medicine,2023,42(08):824-830. DOI： 10.16025/j.1674-1307.2023.08.003.
摘要
目的,2,探讨痰热清注射液（TRQ）联用头孢他啶（CAZ）对铜绿假单胞菌（,Pseudomonas aeruginosa，,PA）的体外耐药敏化作用。,方法,2,选取PA敏感菌株（ATCC 27853）和多重耐药菌株（1508032、1608016、1708116、D1、D2、D5）作为实验菌株，选择指南推荐治疗PA的9种抗生素进行研究。首先采用最小抑菌浓度（MIC）、分级抑菌浓度指数（FICI）筛选出与TRQ联用效果最佳的抗生素；然后通过生长曲线、杀菌曲线以及遗传稳定性实验，分析最佳组合对PA的耐药敏化作用。,结果,2,TRQ与CAZ联用是对PA耐药敏化的最佳组合，对敏感菌（ATCC 27853）和多重耐药菌株（1508032、1608016、1708116、D1、D2、D5）均具有协同和相加作用；生长曲线表明TRQ与CAZ联用对PA具有显著的生长抑制作用；杀菌曲线表明TRQ与CAZ联用可显著增强CAZ对PA的杀伤活性。耐药诱导实验表明TRQ与CAZ联用的耐药敏化方式可能有2种，一是可使敏感菌株ATCC 27853维持对CAZ的敏感性，抑制耐药的产生；二是可使临床耐药菌株MDR-PA 1508032恢复对CAZ的敏感性，并抑制耐药发展。遗传稳定性实验表明，TRQ与CAZ联用后的菌株进行空培养5代期间耐药敏化作用未发生显著变化，具有稳定遗传的特点。,结论,2,TRQ与CAZ联用可增强CAZ对PA的杀伤作用，恢复PA对CAZ的敏感性，并抑制耐药发展，且该敏化作用具有一定的遗传稳定性。
Abstract
Objective,2,To study the drug-resistance sensitization effect of Tanreqing injection （TRQ） combined with ceftazidime （CAZ） on, pseudomonas aeruginosa, （PA） ,in vitro.,Methods,2,Sensitive strain （ATCC 27853） and multi-drug resistant strains （1508032，1608016，1708116，D1，D2，D5） of PA were selected as experimental strains，and 9 antibiotics recommended by the guidelines for the treatment of PA were selected for study.First， minimum inhibitory concentration （MIC） and fractional inhibitory concentration Index （FICI） were used to select the best antibiotics for combination with TRQ. Then， through growth curve， time-kill curve and genetic stability tests， the sensitization of the best combination to PA resistance was analyzed.,Results,2,The combination of TRQ and CAZ was the optimum compatibility for drug-resistance sensitization， which had synergistic and additive effects against sensitive bacteria （ATCC 27853） and multi-resistant strains （1508032， 1608016， 1708116， D1， D2， D5）. The growth curve showed that TRQ combined with CAZ had significant inhibitory effect on the growth of PA. The time-kill curve showed that TRQ combined with CAZ significantly enhanced the killing activity of CAZ against PA. Drug-resistance induction experiments suggested that there were two possible ways of sensitization of TRQ combined with CAZ. Firstly， it could maintain the sensitivity of sensitive strain ATCC 27853 to CAZ and inhibit the development of drug resistance. Secondly， it could restore the sensitivity of clinical drug-resistant strain MDR-PA 1508032 to CAZ and inhibit the development of drug resistance. The genetic stability test indicated that there was no significant difference in drug-resistance sensitization after intervention of combination of TRQ and CAZ during the five generations of empty culture， and the drug-resistance sensitization of TRQ combined with CAZ to PA was stable.,Conclusion,2,The combination of TRQ and CAZ could enhance the killing effect of CAZ on PA， restore the sensitivity of PA to CAZ， and inhibit the drug-resistance development with certain genetic stability.
关键词
痰热清注射液头孢他啶耐药敏化铜绿假单胞菌
Keywords
Tanreqing injectionceftazidimeresistance sensitizationpseudomonas aeruginosa
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