Wang Lingbo, Zhang Ying, Liu Shixing, Huang Na, Zeng Weiliang, Xu Wenya, Zhou Tieli, Shen Mo
Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China.
School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, People's Republic of China.
Infect Drug Resist. 2021 Nov 5;14:4619-4627. doi: 10.2147/IDR.S331345. eCollection 2021.
The emergence and spread of linezolid-resistant () have emerged as a serious threat to human health globally. Therefore, this study aims to compare the anti-microbic as well as the anti-biofilm activity of linezolid, tedizolid, and radezolid against linezolid-resistant .
A total of 2128 isolates were assessed from the First Affiliated Hospital of Wenzhou Medical University from 2011 to 2019. Antibiotic sensitivity was evaluated using the micro broth dilution method. Oxazolidinone-resistant chromosomal and plasmid-borne genes such as , and were detected by PCR and then sequenced to detect the presence of mutations in the domain V of the 23S rRNA and the ribosomal proteins L3, L4, and L22. Conjugation experiments were conducted using the broth method. The inhibition and eradication of biofilm were evaluated through crystal violet staining, whereas the efflux pump activities were detected by agar dilution.
Out of 2128 isolated , 71 (3.34%) were linezolid-resistant isolates in which the MICs of tedizolid and radezolid ranged from 1 to 4 μg/mL and 0.5-1 μg/mL, respectively. The MIC/MIC of tedizolid and radezolid were 4 and 8-fold lower than the linezolid, respectively. Out of 71 resistant isolates, 57 (80.28%) carried , 1 (1.41%) carried , 4 (5.63%) carried and , and 6 (8.45%) carried and , with no mutations of 23S rRNA gene and ribosomal proteins L3, L4, and L22. Besides, the transfer rate of the , and was 17.91%, 0% and 0%, respectively. Radezolid showed more effectiveness in eradicating biofilm (8 × MIC). However, tedizolid was more effective than radezolid and linezolid in inhibiting the biofilm formation (1/4 MIC, 1/8MIC, and 1/16MIC). Additionally, in combination with CCCP, the MICs of radezolid in all linezolid-resistant isolates decreased ≥4-fold.
Radezolid showed greater antimicrobial activity than tedizolid and linezolid against linezolid-resistant . However, both tedizolid and radezolid showed differential activity on biofilm inhibition, eradication, and efflux pump compared to linezolid. Thus, our study might bring important clinical value in the application of these drugs for resistant pathogenic strains.
耐利奈唑胺粪肠球菌的出现和传播已成为全球人类健康的严重威胁。因此，本研究旨在比较利奈唑胺、替地唑胺和雷地唑胺对耐利奈唑胺粪肠球菌的抗菌及抗生物膜活性。
对2011年至2019年温州医科大学附属第一医院分离出的2128株粪肠球菌进行评估。采用微量肉汤稀释法评估抗生素敏感性。通过PCR检测耐恶唑烷酮的染色体和质粒携带基因，如 、 和 ，然后进行测序以检测23S rRNA结构域V以及核糖体蛋白L3、L4和L22中突变的存在。使用肉汤法进行接合试验。通过结晶紫染色评估生物膜的抑制和根除情况，而通过琼脂稀释法检测外排泵活性。
在2128株分离的粪肠球菌中，71株（3.34%）为耐利奈唑胺菌株，其中替地唑胺和雷地唑胺的MIC分别为1至4μg/mL和0.5 - 1μg/mL。替地唑胺和雷地唑胺的MIC/MIC分别比利奈唑胺低4倍和8倍。在71株耐药菌株中，57株（80.28%）携带 ，1株（1.41%）携带 ，4株（5.63%）携带 和 ，6株（8.45%）携带 和 ，23S rRNA基因以及核糖体蛋白L3、L4和L22无突变。此外， 、 和 的转移率分别为17.91%、0%和0%。雷地唑胺在根除生物膜（8×MIC）方面表现出更高的有效性。然而，替地唑胺在抑制生物膜形成（1/4 MIC、1/8 MIC和1/16 MIC）方面比利奈唑胺和雷地唑胺更有效。此外，与CCCP联合使用时，所有耐利奈唑胺菌株中雷地唑胺的MIC降低≥4倍。
雷地唑胺对耐利奈唑胺粪肠球菌的抗菌活性比利奈唑胺和替地唑胺更强。然而，与利奈唑胺相比，替地唑胺和雷地唑胺在生物膜抑制、根除和外排泵方面表现出不同的活性。因此，我们的研究可能为这些药物在耐药病原菌中的应用带来重要的临床价值。
