粘菌素耐药性：从实验室研究到现代临床管理
Colistin Resistance: From Laboratory Research to Modern Clinical Management.
摘要(中文译文)
黏菌素是一种20世纪中期引入的多黏菌素类抗生素，作为治疗多重耐药（MDR）革兰阴性菌所致感染的最后防线药物，已重新获得临床重视。碳青霉烯耐药病原体的全球传播加剧了黏菌素的使用，导致耐药性令人担忧地上升。本综述旨在全面、及时地综合黏菌素的药理学特征、耐药机制、流行病学以及当前和新兴的治疗策略。本文进行了叙述性文献综述，涵盖黏菌素的化学结构、作用机制、药效学、临床应用、给药方案及耐药性相关研究。审查了染色体介导和质粒介导的耐药机制、检测方法、流行病学趋势及临床结局的数据。此外，还分析了基于黏菌素的治疗策略及新型非抗生素方法的证据。黏菌素对许多MDR革兰阴性病原体仍保持活性，包括、、和；然而，全球范围内耐药性的报道日益增多。染色体介导的脂质A修饰和质粒介导的mcr基因均导致耐药，异质性耐药给诊断和治疗带来挑战。碳青霉烯耐药已成为黏菌素使用及随后耐药选择的主要驱动因素。联合治疗、吸入制剂和指南指导下的使用可能改善结局，而抗菌肽、噬菌体、纳米颗粒、光动力疗法和基于CRISPR的技术等新兴替代方案显示出前景。黏菌素耐药率的不断攀升威胁着这一关键最后防线抗生素的有效性。优化使用、加强耐药监测、准确的检测方法以及开发创新治疗策略，对于保持黏菌素的临床效用和应对日益加重的MDR革兰阴性感染负担至关重要。
Abstract
Colistin, a polymyxin antibiotic introduced in the mid-20th century, has regained clinical importance as a last-resort agent for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. The global dissemination of carbapenem-resistant pathogens has intensified colistin use, leading to a concerning rise in resistance. This review aims to provide a comprehensive and up-to-date synthesis of colistin's pharmacological characteristics, resistance mechanisms, epidemiology, and current and emerging therapeutic strategies. A narrative review of the literature was conducted, encompassing studies on the chemistry, mechanism of action, pharmacodynamics, clinical use, dosing, and resistance to colistin. Data on chromosomal and plasmid-mediated resistance mechanisms, detection methodologies, epidemiological trends, and clinical outcomes were examined. In addition, evidence on colistin-based treatment strategies and novel non-antibiotic approaches was analyzed. Colistin remains active against many MDR Gram-negative pathogens, including , , and ; however, resistance is increasingly reported worldwide. Both chromosomally mediated modifications of lipid A and plasmid-mediated mcr genes contribute to resistance, with heteroresistance posing diagnostic and therapeutic challenges. Carbapenem resistance has emerged as a major driver of colistin use and subsequent resistance selection. Combination therapies, inhaled formulations, and guideline-directed use may improve outcomes, while emerging alternatives such as antimicrobial peptides, bacteriophages, nanoparticles, photodynamic therapy, and CRISPR-based technologies show promise. The escalating prevalence of colistin resistance threatens the effectiveness of this critical last-line antibiotic. Optimized use, robust resistance surveillance, accurate detection methods, and the development of innovative therapeutic strategies are essential to preserve colistin's clinical utility and address the growing burden of MDR Gram-negative infections.
如何引用
AMA
Hakan Erdem, Gulden Yilmaz-Tehli. Colistin Resistance: From Laboratory Research to Modern Clinical Management.. Antibiotics (Basel, Switzerland). 2026; doi:10.3390/antibiotics15030259.
APA
Hakan Erdem, Gulden Yilmaz-Tehli (2026). Colistin Resistance: From Laboratory Research to Modern Clinical Management.. Antibiotics (Basel, Switzerland). https://doi.org/10.3390/antibiotics15030259
GB/T 7714
Hakan Erdem, Gulden Yilmaz-Tehli. Colistin Resistance: From Laboratory Research to Modern Clinical Management.[J]. Antibiotics (Basel, Switzerland), 2026 doi:10.3390/antibiotics15030259.
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