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用于细菌抑制的环丙沙星和利福平双载抗生素生物聚合物壳聚糖海绵

Ciprofloxacin and Rifampin Dual Antibiotic-Loaded Biopolymer Chitosan Sponge for Bacterial Inhibition.

作者信息

Wells Carlos M, Beenken Karen E, Smeltzer Mark S, Courtney Harry S, Jennings Jessica A, Haggard Warren O

机构信息

Department of Biomedical Engineering, University of Memphis, 3796 Norriswood Avenue, Memphis, TN 38111.

The Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205.

出版信息

Mil Med. 2018 Mar 1;183(suppl_1):433-444. doi: 10.1093/milmed/usx150.

Abstract

Complex extremity wounds in Wounded Warriors can become contaminated with microbes, which may cause clinical outcomes resulting in amputation, morbidity, or even fatality. Local delivery of multiple or broad-spectrum antibiotics allows practicing clinicians treatment solutions that may inhibit biofilm formation. Propagation of vancomycin-resistant Staphylococcus aureus is also a growing concern. The development of vancomycin-resistant S. aureus has become a critical challenge in nosocomial infection prevention in the USA, but to date has seen little occurrence in osteomyelitis. As an alternative, locally delivered ciprofloxacin and rifampin were investigated in a preclinical model for the prevention of biofilm in complex extremity wounds with implanted fixation device. In vitro assays demonstrated ciprofloxacin and rifampin possess an additive effect against Gram-negative Pseudomonas aeruginosa and were actively eluted from a chitosan sponge based local delivery system. In an in vivo orthopedic hardware-associated polymicrobial model (S. aureus and Escherichia coli) the combination was able to achieve complete clearance of both bacterial strains. E. coli was detected in bone of untreated animals, but did not form biofilm on wires. Results reveal the clinical potential of antibiotic-loaded chitosan sponges to inhibit infection through tailored antibiotic selection at desired concentrations with efficacy towards biofilm inhibition.

摘要

受伤战士的复杂肢体伤口可能会被微生物污染,这可能导致截肢、发病甚至死亡等临床后果。局部递送多种或广谱抗生素可为临床医生提供可能抑制生物膜形成的治疗方案。耐万古霉素金黄色葡萄球菌的传播也日益受到关注。耐万古霉素金黄色葡萄球菌的出现已成为美国医院感染预防中的一项关键挑战,但迄今为止在骨髓炎中很少发生。作为一种替代方法,在一个临床前模型中研究了局部递送环丙沙星和利福平,以预防植入固定装置的复杂肢体伤口中的生物膜。体外试验表明,环丙沙星和利福平对革兰氏阴性铜绿假单胞菌具有相加作用,并能从基于壳聚糖海绵的局部递送系统中有效洗脱。在一个体内骨科硬件相关的多微生物模型(金黄色葡萄球菌和大肠杆菌)中,该组合能够实现两种细菌菌株的完全清除。在未治疗动物的骨骼中检测到大肠杆菌,但在金属丝上未形成生物膜。结果揭示了载有抗生素的壳聚糖海绵通过选择所需浓度的特定抗生素来抑制感染并有效抑制生物膜的临床潜力。

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