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类脂肽抗生素联合方案提高体外幽门螺杆菌生物膜根除率:与传统三联疗法的比较。

Rhamnolipid-involved antibiotics combinations improve the eradication of Helicobacter pylori biofilm in vitro: A comparison with conventional triple therapy.

机构信息

Lab of Pharmaceutic, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR China.

Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China; Department of Geriatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, PR China.

出版信息

Microb Pathog. 2019 Jun;131:112-119. doi: 10.1016/j.micpath.2019.04.001. Epub 2019 Apr 2.

Abstract

Antibiotics resistance of H. pylori has been increasing constantly accompanied with decreasing clearance rate clinically, which is demonstrated to be closely related to biofilms with higher resistance than planktonic bacteria for the dense extracellular polymeric substances. Rhamnolipid (RHL) is proved to not only damage the structure of biofilm, but also potentially inhibit bacterial adhesion. To investigate if RHL could promote eradicating rate of the conventional triple therapy to H. pylori biofilm and hence attenuate the resistance and relapse of H. pylori, first-line antibiotics clarithromycin (CLR), amoxicillin (AMX) or/and proton pump inhibitor (PPI) involved single, dual or triple therapies were compared with RHL-containing drug combinations on eradicating H. pylori biofilm. The residual biofilm biomass, the survival of bacteria inside the remaining biofilm and the planktonic bacteria dispersed from the biofilm after treatment were tested. Combination with RHL significantly improved the ability of antibiotics to eradicate H. pylori biofilm, especially RHL combined with AMX and PPI could eradicate more than 95% of biofilm showing much more effective ability than the conventional triple therapy CLR + AMX + PPI. Additionally, the combination of RHL and antibiotics could effectively inhibit the biofilm formation at lower concentration. Thus, RHL might be used as a potential antibiotic adjuvant on anti-H. pylori therapy to enhance eradicating ability of antibiotics to biofilms.

摘要

幽门螺杆菌的抗生素耐药性一直在不断增加,同时临床清除率也在下降,这被证明与生物膜密切相关,生物膜的耐药性比浮游细菌更高,因为其具有更密集的细胞外聚合物。鼠李糖脂(Rhamnolipid,RHL)已被证明不仅可以破坏生物膜的结构,而且还可能抑制细菌的黏附。为了研究 RHL 是否可以提高常规三联疗法对幽门螺杆菌生物膜的根除率,从而减轻幽门螺杆菌的耐药性和复发,本研究首先比较了包含 RHL 的药物组合与单一、双重或三重治疗方案(涉及一线抗生素克拉霉素(CLR)、阿莫西林(AMX)或/和质子泵抑制剂(PPI))在根除幽门螺杆菌生物膜方面的疗效。检测了残留生物膜的生物量、残留生物膜内细菌的存活情况以及从生物膜中分散出来的浮游细菌。与 RHL 联合使用可显著提高抗生素根除幽门螺杆菌生物膜的能力,尤其是 RHL 与 AMX 和 PPI 联合使用,可根除超过 95%的生物膜,其效果明显优于常规三联疗法 CLR+AMX+PPI。此外,RHL 与抗生素联合使用可以在较低浓度下有效地抑制生物膜的形成。因此,RHL 可能作为一种潜在的抗生素佐剂,用于抗幽门螺杆菌治疗,以增强抗生素对生物膜的根除能力。

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