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双氯芬酸对左氧氟沙星耐药菌株的抗菌及抗生物膜活性;着重于双氯芬酸的重新利用

Antibacterial and antibiofilm activities of diclofenac against levofloxacin-resistant isolates; emphasizing repurposing of diclofenac.

作者信息

El-Soudany Ingy, Abdelwahab Ibrahim A, Yakout Marwa Atef

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.

出版信息

Iran J Microbiol. 2024 Apr;16(2):166-175. doi: 10.18502/ijm.v16i2.15349.

Abstract

BACKGROUND AND OBJECTIVES

is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the antibacterial and antibiofilm effects of diclofenac and levofloxacin/diclofenac combination against levofloxacin resistant isolates.

MATERIALS AND METHODS

Minimum inhibitory concentration was determined using broth microdilution method for levofloxacin, diclofenac, and levofloxacin/diclofenac combination. Biofilm forming capacity and biofilm inhibition assay were determined. Relative gene expression was measured for efflux pump genes; , and genes and biofilm related genes , and without and with diclofenac and the combination.

RESULTS

Diclofenac demonstrated MIC of 1 mg/ml. The combination-with ½ MIC diclofenac-showed synergism where levofloxacin MIC undergone 16-32 fold decrease. All the isolates that overexpressed and showed a significant decrease in gene expression in presence of diclofenac or the combination. The mean percentage inhibition of biofilm formation with diclofenac and the combination was 40.59% and 46.49%, respectively. This agreed with biofilm related genes expression investigations.

CONCLUSION

Diclofenac showed an antibacterial effect against The combination showed synergism, significant reduction in biofilm formation and in the relative level of gene expression. Furthermore, it can potentiate the levofloxacin activity or revert its resistance.

摘要

背景与目的

是一种引起医院感染的机会致病菌。双氯芬酸是一种抗炎药物,被认为是非抗生素药物。本研究评估了双氯芬酸以及左氧氟沙星/双氯芬酸组合对左氧氟沙星耐药菌株的抗菌和抗生物膜作用。

材料与方法

采用肉汤微量稀释法测定左氧氟沙星、双氯芬酸以及左氧氟沙星/双氯芬酸组合的最低抑菌浓度。测定生物膜形成能力和生物膜抑制试验。测定外排泵基因、以及基因和生物膜相关基因、在有无双氯芬酸及组合情况下的相对基因表达。

结果

双氯芬酸的最低抑菌浓度为1mg/ml。与½最低抑菌浓度双氯芬酸的组合显示出协同作用,左氧氟沙星的最低抑菌浓度降低了16 - 32倍。所有过表达和的分离株在存在双氯芬酸或组合时基因表达均显著降低。双氯芬酸和组合对生物膜形成的平均抑制百分比分别为40.59%和46.49%。这与生物膜相关基因表达研究结果一致。

结论

双氯芬酸对显示出抗菌作用。该组合显示出协同作用,生物膜形成及基因表达相对水平显著降低。此外,它可以增强左氧氟沙星的活性或逆转其耐药性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed9f/11162161/e4692b1f7899/IJM-16-166-g001.jpg

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