依拉环素与替加环素对中国临床分离株的抗菌活性及耐药机制比较
Comparison of antimicrobial activities and resistance mechanisms of eravacycline and tigecycline against clinical isolates in China.
作者信息
Chen Xiandi, Li Yitan, Lin Yingzhuo, Guo Yingyi, He Guohua, Wang Xiaohu, Wang Mingzhen, Xu Jianbo, Song Mingdong, Tan Xixi, Zhuo Chao, Lin Zhiwei
机构信息
Key Laboratory of Respiratory Disease, People's Hospital of Yangjiang, Yangjiang, China.
Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
出版信息
Front Microbiol. 2024 Sep 24;15:1417237. doi: 10.3389/fmicb.2024.1417237. eCollection 2024.
Tigecycline (TGC) is currently used to treat carbapenem-resistant (CRAB) infections, while eravacycline (ERV), a new-generation tetracycline, holds promise as a novel therapeutic option for these infections. However, differences in resistance mechanism between ERV and TGC against remain unclear. This study sought to compare the characteristics and mechanisms of ERV and TGC resistance among clinical isolates. A total of 492 isolates, including 253 CRAB and 239 carbapenem-sensitive (CSAB) isolates, were collected from hospitalized patients in China. The MICs of ERV and TGC against were determined by broth microdilution. Genetic mutations and expressions of , and in resistant strains were examined by PCR and qPCR, respectively. The recombination experiments were used to verify the resistance mechanism of ERV and TGC in . The MIC of ERV in CRAB and CSAB isolates were lower than those of TGC. A total of 24 strains resistant to ERV and/or TGC were categorized into three groups: only ERV-resistant ( = 2), both ERV- and TGC-resistant ( = 7), and only TGC-resistant ( = 15). ST208 (75%, = 18) was a major clone that has disseminated in all three groups. The IS insertion in was identified in 66.7% (6/9) of strains in the only ERV-resistant and both ERV- and TGC-resistant groups, while the IS insertion in was found in 53.3% (8/15) of strains in the only TGC-resistant group. The and expressions were significantly increased in the only ERV-resistant and both ERV- and TGC-resistant groups, while the and expressions were significantly increased and was significantly decreased in the only TGC-resistant group. Expression of with the IS insertion in ERV- and TGC-sensitive strains significantly increased the ERV and TGC MICs and upregulated and expressions. Complementation of the wildtype in TGC-resistant strains with the IS insertion in restored TGC sensitivity and significantly downregulated expression. In conclusion, our data illustrates that ERV is more effective against clinical isolates than TGC. ERV resistance is correlated with the IS insertion in , while TGC resistance is associated with the IS insertion in or in
替加环素（TGC）目前用于治疗耐碳青霉烯类鲍曼不动杆菌（CRAB）感染，而新一代四环素类药物依拉环素（ERV）有望成为这类感染的新型治疗选择。然而，ERV和TGC对鲍曼不动杆菌的耐药机制差异尚不清楚。本研究旨在比较临床分离株中ERV和TGC耐药的特征及机制。从中国住院患者中收集了共492株分离株，包括253株CRAB和239株碳青霉烯类敏感鲍曼不动杆菌（CSAB）分离株。采用肉汤微量稀释法测定ERV和TGC对鲍曼不动杆菌的最低抑菌浓度（MIC）。分别通过聚合酶链反应（PCR）和实时定量聚合酶链反应（qPCR）检测耐药菌株中blaOXA-23、blaOXA-51-like和omp33的基因突变及表达情况。利用blaOXA-23重组实验验证ERV和TGC对鲍曼不动杆菌的耐药机制。ERV在CRAB和CSAB分离株中的MIC低于TGC。共24株对ERV和/或TGC耐药的菌株分为三组：仅对ERV耐药（n = 2）、对ERV和TGC均耐药（n = 7）、仅对TGC耐药（n = 15）。ST208（75%，n = 18）是在所有三组中均有传播的主要克隆型。在仅对ERV耐药组和对ERV与TGC均耐药组中，66.7%（6/9）的菌株检测到blaOXA-23基因座插入IS Aba1，而在仅对TGC耐药组中，53.3%（8/15）的菌株检测到blaOXA-51-like基因座插入IS Aba1。在仅对ERV耐药组和对ERV与TGC均耐药组中，blaOXA-23和omp33的表达显著增加，而在仅对TGC耐药组中，blaOXA-51-like和omp33的表达显著增加且blaOXA-23显著降低。在ERV和TGC敏感菌株中，携带IS插入的blaOXA-23表达显著增加了ERV和TGC的MIC，并上调了blaOXA-23和omp33的表达。对携带blaOXA-51-like基因座插入IS Aba1的TGC耐药菌株补充野生型blaOXA-51-like可恢复TGC敏感性，并显著下调blaOXA-51-like表达。总之，我们的数据表明，ERV对鲍曼不动杆菌临床分离株的疗效优于TGC。ERV耐药与blaOXA-23基因座插入IS Aba1相关，而TGC耐药与blaOXA- 51-like基因座插入IS Aba1或blaOXA-23有关。
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