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在猪角膜炎模型中增加对常用抗生素的耐受性。

Increased tolerance to commonly used antibiotics in a porcine keratitis model.

机构信息

Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S10 2TN, UK.

National Institute for Health and Care Research, University of Leeds, Leeds LS2 9JT, UK.

出版信息

Microbiology (Reading). 2024 May;170(5). doi: 10.1099/mic.0.001459.

Abstract

. Bacterial keratitis, particularly caused by , is challenging to treat because of multi-drug tolerance, often associated with the formation of biofilms. Antibiotics in development are typically evaluated against planktonic bacteria in a culture medium, which may not accurately represent the complexity of infections . Developing a reliable, economic keratitis model that replicates some complexity of tissue infections could facilitate a deeper understanding of antibiotic efficacy, thus aiding in the optimization of treatment strategies for bacterial keratitis.. Here we investigated the efficacy of three commonly used antibiotics (gentamicin, ciprofloxacin and meropenem) against cytotoxic strain PA14 and invasive strain PA01 using an porcine keratitis model.. Both strains of were susceptible to the MIC of the three tested antibiotics. However, significantly higher concentrations were necessary to inhibit bacterial growth in the minimum biofilm eradication concentration (MBEC) assay, with both strains tolerating concentrations greater than 512 mg l of meropenem. When MIC and higher concentrations than MBEC (1024 mg l) of antibiotics were applied, ciprofloxacin exhibited the highest potency against both strains, followed by meropenem, while gentamicin showed the least potency. Despite this, none of the antibiotic concentrations used effectively cleared the infection, even after 18 h of continuous exposure. Further exploration of antibiotic concentrations and aligning dosing with clinical studies to validate the model is needed. Nonetheless, our porcine keratitis model could be a valuable tool for assessing antibiotic efficacy.

摘要

细菌性角膜炎,特别是由 引起的,由于多药耐药性,通常与生物膜的形成有关,因此治疗极具挑战性。正在开发的抗生素通常在培养基中针对浮游细菌进行评估,而这可能无法准确反映感染的复杂性。开发一种可靠、经济的 角膜炎模型,复制组织感染的某些复杂性,可以促进对抗生素疗效的深入了解,从而有助于优化细菌性角膜炎的治疗策略。在这里,我们使用猪角膜炎模型研究了三种常用抗生素(庆大霉素、环丙沙星和美罗培南)对细胞毒性菌株 PA14 和侵袭性菌株 PA01 的疗效。两种 菌株均对三种测试抗生素的 MIC 敏感。然而,在最低生物膜清除浓度 (MBEC) 测定中,抑制细菌生长所需的浓度显着更高,两种菌株均耐受大于 512 mg l 的美罗培南浓度。当应用 MIC 和高于 MBEC(1024 mg l)的抗生素浓度时,环丙沙星对两种 菌株的效力最高,其次是美罗培南,而庆大霉素的效力最低。尽管如此,即使在 18 小时的连续暴露后,也没有任何抗生素浓度能有效清除感染。需要进一步探索抗生素浓度,并将剂量与临床研究相匹配,以验证该模型。尽管如此,我们的 猪角膜炎模型可能是评估抗生素疗效的有用工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cc2/11165664/4c164190907f/mic-170-01459-g001.jpg

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