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载环丙沙星脂质体对环丙沙星耐药及形成生物膜菌株的抗菌活性

The Antimicrobial Activity of Ciprofloxacin-Loaded Niosomes against Ciprofloxacin-Resistant and Biofilm-Forming .

作者信息

Kashef Mona T, Saleh Nehal M, Assar Nouran H, Ramadan Mohammed A

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Department of Microbiology, National Organization for Drug Control and Research, Giza, Egypt.

出版信息

Infect Drug Resist. 2020 Jun 8;13:1619-1629. doi: 10.2147/IDR.S249628. eCollection 2020.

Abstract

PURPOSE

The threat of antimicrobial resistance is increasing worldwide. Niosomes are a new drug delivery system that enhances the antimicrobial potential of antibiotics. We hereby aim to evaluate the antimicrobial and antibiofilm activity of ciprofloxacin-loaded niosomes.

METHODS

The antimicrobial susceptibility of clinical isolates (n=59) was determined by Kirby-Bauer disk diffusion method. Their biofilm formation activity was tested by Christensen's method. Two ciprofloxacin-loaded niosomal formulations were prepared by thin-film hydration method, and their minimum inhibitory concentrations (MIC) were determined by agar dilution method, against ciprofloxacin-resistant and biofilm-forming isolates (n=24). Their ability to inhibit biofilm formation and eradicate already formed biofilms was evaluated and further confirmed by scanning electron microscope images. Non-synonymous mutations, in a quinolone resistance-determining regions of isolates, were detected by polymerase chain reaction.

RESULTS

Most of the isolates were methicillin- (47/59) and ciprofloxacin-resistant (45/59). All except two isolates were capable of biofilm production. Niosomal preparation I reduced ciprofloxacin MIC by twofold in four isolates, whereas preparation II reduced ciprofloxacin MIC of most isolates by 8- to 32-fold, with three isolates that became ciprofloxacin-susceptible. Non-synonymous mutations were detected in isolates that maintained phenotypic ciprofloxacin resistance against ciprofloxacin-loaded niosomal preparation II. Ciprofloxacin-loaded niosomes reduced the minimum biofilm inhibitory concentration and the minimum biofilm eradication concentration in 58% and 62% of the tested isolates, respectively.

CONCLUSION

Ciprofloxacin-loaded niosomes can restore ciprofloxacin activity against resistant isolates. To our knowledge, this is the first report on the inhibition of biofilm formation and eradication of formed biofilms by ciprofloxacin-loaded niosomes.

摘要

目的

全球范围内,抗菌药物耐药性的威胁日益增加。脂质体是一种新型药物递送系统,可增强抗生素的抗菌潜力。我们旨在评估载有环丙沙星的脂质体的抗菌和抗生物膜活性。

方法

采用 Kirby-Bauer 纸片扩散法测定临床分离株(n = 59)的药敏性。用 Christensen 法检测其生物膜形成活性。通过薄膜水化法制备两种载有环丙沙星的脂质体制剂,采用琼脂稀释法测定其对耐环丙沙星和形成生物膜的分离株(n = 24)的最低抑菌浓度(MIC)。通过扫描电子显微镜图像评估并进一步证实它们抑制生物膜形成和根除已形成生物膜的能力。通过聚合酶链反应检测分离株喹诺酮耐药决定区的非同义突变。

结果

大多数分离株对甲氧西林(47/59)和环丙沙星耐药(45/59)。除两株分离株外,所有分离株均能产生生物膜。脂质体制剂 I 使 4 株分离株的环丙沙星 MIC 降低了两倍,而制剂 II 使大多数分离株的环丙沙星 MIC 降低了 8 至 32 倍,有 3 株分离株对环丙沙星变得敏感。在对载有环丙沙星的脂质体制剂 II 保持环丙沙星表型耐药性的分离株中检测到非同义突变。载有环丙沙星的脂质体分别降低了 58%和 62%受试分离株的最低生物膜抑制浓度和最低生物膜根除浓度。

结论

载有环丙沙星的脂质体可恢复环丙沙星对耐药分离株的活性。据我们所知,这是关于载有环丙沙星的脂质体抑制生物膜形成和根除已形成生物膜的首次报道。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/187a/7294563/c4625af17846/IDR-13-1619-g0001.jpg

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