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头孢美唑、氟氧头孢和美罗培南对产超广谱β-内酰胺酶大肠埃希菌的浮游细胞有效,但对其生物膜无效。

Cefmetazole, flomoxef, and meropenem are effective against planktonic cells but not biofilms of extended-spectrum β-lactamase-producing Escherichia coli.

作者信息

Hatayama Nami, Sato Yoshinori, Tahira Rika, Hori Toki, Tansho-Nagakawa Shigeru, Ono Yasuo, Yoshino Yusuke

机构信息

Department of Microbiology and Immunology, Teikyo University School of Medicine, Itabashi-ku, Tokyo, 173-8605, Japan.

Faculty of Health and Medical Science, Teikyo Heisei University, Toshima-ku, 170-8445, Tokyo, Japan.

出版信息

BMC Microbiol. 2025 Jul 2;25(1):387. doi: 10.1186/s12866-025-04088-z.

Abstract

BACKGROUND

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli is a potential  public health threat through its spread into the environment. Cefmetazole (CMZ) and flomoxef (FMOX) are highly effective alternatives to meropenem (MEM) for the management of ESBL-producing E. coli infections. However, their antimicrobial effects on biofilms remain unclear. Therefore, this study aimed to elucidate the inhibitory and bactericidal effects of CMZ, FMOX, and MEM on the biofilms formed by ESBL-producing E. coli.

METHODS

Three ESBL-producing E. coli clinical isolates with biofilm-forming abilities (strains F6, F11, and U3) were used in the present study. Biofilm formation and viability assay kits were used to assess the inhibitory and bactericidal effects of these antibiotics on the biofilm-dispersed and biofilm cells of these strains. Scanning electron microscopy (SEM) was used to acquire images of the biofilms treated with these antibiotics.

RESULTS

CMZ and MEM exerted significant inhibitory effects on the growth of biofilm-dispersed cells of all three strains at 1 × minimum inhibitory concentration (MIC). FMOX also exerted significant inhibitory effects on the growth of biofilm-dispersed cells of F11 strain at 1 × MIC; however, it exerted inhibitory effects on the growth of biofilm-dispersed cells of strains F6 and U3 in a concentration-dependent manner. CMZ, FMOX, and MEM exerted different bactericidal effects on biofilm-dispersed cells. CMZ exerted significant inhibitory effects on biofilm formation in all strains at 1 × MIC, whereas MEM exerted significant inhibitory effects on biofilm formation in the F6 and F11 strains at 1 × MIC. FMOX induced biofilm formation in F6 and U3 strains at concentrations between 1 × and 4 × MICs. Notably, CMZ, FMOX, and MEM did not exert bactericidal effects on the biofilm cells of any strain. SEM analysis revealed the induction of bacterial filamentation in the presence of CMZ and FMOX and spheroplast formation in the presence of MEM at 1 × MIC.

CONCLUSIONS

CMZ, FMOX, and MEM exhibited varying antimicrobial effects against ESBL-producing E. coli biofilms. Notably, FMOX may increase biofilm formation by inducing strong morphological changes. CMZ and FMOX are effective alternatives to MEM for ESBL-producing E. coli infections; however, their use requires the consideration of biofilm formation.

摘要

背景

产超广谱β-内酰胺酶(ESBL)的大肠杆菌通过传播到环境中对公众健康构成潜在威胁。头孢美唑(CMZ)和氟氧头孢(FMOX)是美罗培南(MEM)治疗产ESBL大肠杆菌感染的高效替代药物。然而,它们对生物膜的抗菌作用尚不清楚。因此,本研究旨在阐明CMZ、FMOX和MEM对产ESBL大肠杆菌形成的生物膜的抑制和杀菌作用。

方法

本研究使用了三株具有生物膜形成能力的产ESBL大肠杆菌临床分离株(菌株F6、F11和U3)。使用生物膜形成和活力测定试剂盒评估这些抗生素对这些菌株的生物膜分散细胞和生物膜细胞的抑制和杀菌作用。使用扫描电子显微镜(SEM)获取用这些抗生素处理的生物膜的图像。

结果

CMZ和MEM在1×最小抑菌浓度(MIC)时对所有三株菌株的生物膜分散细胞的生长均有显著抑制作用。FMOX在1×MIC时对F11菌株的生物膜分散细胞的生长也有显著抑制作用;然而,它对F6和U3菌株的生物膜分散细胞的生长呈浓度依赖性抑制作用。CMZ、FMOX和MEM对生物膜分散细胞有不同的杀菌作用。CMZ在1×MIC时对所有菌株的生物膜形成均有显著抑制作用,而MEM在1×MIC时对F6和F11菌株的生物膜形成有显著抑制作用。FMOX在1×至4×MIC浓度范围内诱导F6和U3菌株形成生物膜。值得注意的是,CMZ、FMOX和MEM对任何菌株的生物膜细胞均无杀菌作用。SEM分析显示,在1×MIC时,CMZ和FMOX存在时诱导细菌丝状化,MEM存在时形成原生质球。

结论

CMZ、FMOX和MEM对产ESBL大肠杆菌生物膜表现出不同的抗菌作用。值得注意的是,FMOX可能通过诱导强烈的形态变化增加生物膜形成。CMZ和FMOX是治疗产ESBL大肠杆菌感染的MEM的有效替代药物;然而,它们的使用需要考虑生物膜形成。

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