2026 年第 2 期 第 21 卷

大蒜素逆转NDM-1型耐碳青霉烯类肺炎克雷伯菌对美罗培南耐药的作用研究

Study on the effect of allicin in reversing the resistance of NDM-1-type carbapenem-resistant Klebsiella pneumoniae to meropenem

作者：阮海涛高芳琳詹文芳

英文作者：Ruan Haitao Gao Fanglin Zhan Wenfang

单位：福建中医药大学附属人民医院检验科，福州350004

英文单位：Department of Clinical Laboratory People′s Hospital Affiliated to Fujian University of Traditional Chinese Medicine Fuzhou 350004 China

关键词：大蒜素；逆转耐药；NDM-1型；耐碳青霉烯类肺炎克雷伯菌；美罗培南

英文关键词：Allicin;Reversingtheresistance;NDM-1type;Carbapenem-resistantKlebsiellapneumoniae;Meropenem

• 摘要：

• 目的 探究大蒜素逆转NDM-1型耐碳青霉烯类肺炎克雷伯菌(CRKP)对美罗培南耐药的作用。方法 选取5株CRKP菌株，为福建中医药大学附属人民医院临床标本分离株，包括4株携带blaNDM-1的CRKP1～CRKP4、1株不携带blaNDM-1的CRKP5（阴性对照）。①采用微量棋盘稀释法，从5种中药单体（紫草素、杨梅素、黄芩苷、木犀草素、大蒜素）中筛选出逆转NDM-1型CRKP对美罗培南耐药的中药单体，并通过浓度-累积抑菌率进一步证实。②采用标准微量肉汤稀释法，验证大蒜素对4株不同多位点序列分型（MLST分型）的NDM-1型CRKP的逆转作用。③利用基因组二代测序技术检测临床分离菌株的MLST分型与耐药基因携带情况。结果在本实验筛选的5种中药单体中，大蒜素与美罗培南联合使用时对CRKP1的部分抑菌浓度指数（FIC）≤0.5，表明大蒜素与美罗培南联合使用对CRKP1具有协同作用。大蒜素对4株不同MLST分型的NDM-1型CRKP均具有逆转作用。大蒜素与美罗培南联合作用后，4株NDM-1型CRKP的FIC≤0.5，表明大蒜素联合美罗培南对4株NDM-1型CRKP均具有协同作用。对NDM-1型CRKP进行耐药基因分析，结果显示，CRKP1～4菌株均携带blaNDM-1基因，但其MLST分型各不相同，CRKP1～4分别为ST23、ST219、ST63-1LV和ST15，表明这些菌株的亲缘性较低。结论 大蒜素可逆转NDM-1型CRKP对美罗培南耐药，为临床治疗NDM-1型CRKP感染提供了新思路。

• Objective To investigate the effect of allicin on reversing the resistance of NDM-1-type carbapenem-resistant Klebsiella pneumoniae (CRKP) to meropenem.  Methods Five CRKP strains isolated from clinical specimens of People′s Hospital Affiliated to Fujian University of Traditional Chinese Medicine were selected, including 4 blaNDM-1-carrying CRKP strains (CRKP1-CRKP4) and 1 blaNDM-1-non-carrying CRKP strain (CRKP5, negative control). The checkerboard microdilution method was used to screen traditional Chinese medicine monomers (shikonin, myricetin, baicalin, luteolin, allicin) that could reverse the resistance of NDM-1-type CRKP to meropenem, which was further confirmed by concentration cumulative bacteriostatic rate. The standard broth microdilution method was used to verify the reversing effect of allicin on 4 NDM-1-type CRKP strains with different multilocus sequence typing (MLST). Next-generation sequencing technology was employed to detect the MLST typing and antibiotic resistance gene carriage of clinically isolated strains. Results Among the 5 traditional Chinese medicine monomers screened in this experiment, when allicin was combined with meropenem, the fractional inhibitory concentration index (FIC) against CRKP1 was ≤0.5, indicating a synergistic effect between allicin and meropenem on CRKP1. Allicin exhibited a reversing effect on 4 NDM-1-type CRKP strains with different MLST types. After the combination of allicin and meropenem, the FIC of the 4 NDM-1-type CRKP strains was ≤0.5, suggesting that the combination of allicin and meropenem had a synergistic effect on all 4 NDM-1-type CRKP strains. Antibiotic resistance gene analysis of NDM-1-type CRKP showed that strains CRKP1-4 all carried the blaNDM-1 gene, but their MLST types were different: CRKP1-4 were ST23, ST219, ST63-1LV, and ST15, respectively, indicating low relatedness among these strains. Conclusion Allicin can reverse the resistance of NDM-1-type CRKP to meropenem, providing a new idea for the clinical treatment of NDM-1-type CRKP infections.