Colistin-niclosamide effervescent dry suspension combats colistin-resistant Salmonella in vitro and in vivo

IF 3.8 1区 农林科学 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Poultry Science Pub Date : 2024-11-01 DOI:10.1016/j.psj.2024.104492
Junkai Zhang , Qingqing Miao , Xiaoyuan Ma , Dandan He , Yushan Pan , Li Yuan , Yajun Zhai , Gongzheng Hu
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Abstract

The increasing incidence of bacterial infections caused by multidrug-resistant (MDR) Gram-negative bacteria has deepened the need for new effective treatments. It has been reported that niclosamide (NIC) can restore the sensitivity of Gram-negative bacteria to colistin (COL). However, NIC is practically insoluble in water and sparingly soluble in organic solvents, leading to limited therapeutic applications. This study aims to prepare a COL-NIC effervescent dry suspension (CNEDS) and evaluate its antibacterial effect against COL-resistant Salmonella both in vitro and in broiler chickens. With the sedimentation volume ratio as an index, suitable suspending agent, wetting agent, filler and effervescent agent were screened through a single-factor method. The preparation conditions were optimized using the Box-Behnken response surface method to obtain the formulation for CNEDS. The quality evaluation results showed that the successfully prepared CNEDS had a sedimentation volume ratio of 0.99, a drying weight loss of 1.3%, and a re-dispersion capability of 1-2 times, all of which met pharmacopoeial requirements. In terms of pharmacological evaluation, we first demonstrated that CNEDS substantially restored COL sensitivity against COL-resistant bacteria. Subsequently, time-killing analysis, scanning electron microscopy (SEM) and live/dead assays confirmed the antibacterial activity of CNEDS against COL-resistant bacteria. Finally, a Salmonella infection model in broiler chickens was established to further assess the therapeutic effect of CNEDS in vivo. CNEDS improved the survival rate of broiler chickens, reduced the bacterial burden on organs. These findings suggest that CNEDS effectively overcome COL resistance, indicating its potential for the treatment of COL-resistant bacterial infections in broiler chickens.
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可乐定-尼可刹米泡腾干混悬剂可在体外和体内对抗耐可乐定的沙门氏菌。
耐多药(MDR)革兰氏阴性菌引起的细菌感染发病率不断上升,这加深了人们对新的有效治疗方法的需求。据报道,尼可刹米(NIC)可恢复革兰氏阴性菌对可乐定(COL)的敏感性。然而,NIC 几乎不溶于水,在有机溶剂中的溶解度也很低,导致其治疗应用受到限制。本研究旨在制备一种 COL-NIC 泡腾干悬浮剂(CNEDS),并评估其在体外和肉鸡体内对耐 COL 沙门氏菌的抗菌效果。以沉降体积比为指标,通过单因素法筛选出合适的悬浮剂、润湿剂、填料和泡腾剂。采用 Box-Behnken 响应面法对制备条件进行了优化,得到了 CNEDS 的配方。质量评价结果表明,成功制备的 CNEDS 的沉降体积比为 0.99,干燥失重为 1.3%,再分散能力为 1-2 倍,均符合药典要求。在药理评价方面,我们首先证明了 CNEDS 可大幅恢复 COL 对耐 COL 细菌的敏感性。随后,时间杀灭分析、扫描电子显微镜(SEM)和活/死试验证实了 CNEDS 对 COL 耐药菌的抗菌活性。最后,建立了肉鸡沙门氏菌感染模型,以进一步评估 CNEDS 在体内的治疗效果。CNEDS 提高了肉鸡的存活率,减少了细菌对器官的负担。这些研究结果表明,CNEDS 能有效克服 COL 耐药性,表明其具有治疗肉鸡 COL 耐药性细菌感染的潜力。
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上海源叶 sodium alginate
上海源叶 sodium dodecyl sulfate
上海源叶 citric acid
来源期刊
Poultry Science
Poultry Science 农林科学-奶制品与动物科学
CiteScore
7.60
自引率
15.90%
发文量
0
审稿时长
94 days
期刊介绍: First self-published in 1921, Poultry Science is an internationally renowned monthly journal, known as the authoritative source for a broad range of poultry information and high-caliber research. The journal plays a pivotal role in the dissemination of preeminent poultry-related knowledge across all disciplines. As of January 2020, Poultry Science will become an Open Access journal with no subscription charges, meaning authors who publish here can make their research immediately, permanently, and freely accessible worldwide while retaining copyright to their work. Papers submitted for publication after October 1, 2019 will be published as Open Access papers. An international journal, Poultry Science publishes original papers, research notes, symposium papers, and reviews of basic science as applied to poultry. This authoritative source of poultry information is consistently ranked by ISI Impact Factor as one of the top 10 agriculture, dairy and animal science journals to deliver high-caliber research. Currently it is the highest-ranked (by Impact Factor and Eigenfactor) journal dedicated to publishing poultry research. Subject areas include breeding, genetics, education, production, management, environment, health, behavior, welfare, immunology, molecular biology, metabolism, nutrition, physiology, reproduction, processing, and products.
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