Abstract:
The emergence of antimicrobial resistance represents a serious threat to public health and for infections due to multidrug-resistant (MDR) microorganisms, representing one of the most important causes of death worldwide. The renewal of old antimicrobials, such as colistin, has been proposed as a valuable therapeutic alternative to the emergence of the MDR microorganisms. Although colistin is well known to present several adverse toxic effects, its usage in clinical practice has been reconsidered due to its broad spectrum of activity against Gram-negative (GN) bacteria and its important role of \"last resort\" agent against MDR-GN. Despite the revolutionary perspective of treatment with this old antimicrobial molecule, many questions remain open regarding the emergence of novel phenotypic traits of resistance and the optimal usage of the colistin in clinical practice. In last years, several forward steps have been made in the understanding of the resistance determinants, clinical usage, and pharmacological dosage of this molecule; however, different points regarding the role of colistin in clinical practice and the optimal pharmacokinetic/pharmacodynamic targets are not yet well defined. In this review, we summarize the mode of action, the emerging resistance determinants, and its optimal administration in the treatment of infections that are difficult to treat due to MDR Gram-negative bacteria.
摘要:
抗菌素耐药性的出现对公共卫生和多药耐药(MDR)微生物引起的感染构成了严重威胁。代表了全世界最重要的死亡原因之一。旧抗菌药物的更新,比如粘菌素,已被提出作为MDR微生物出现的有价值的治疗替代方案。尽管众所周知粘菌素具有多种不良毒性作用,由于其对革兰氏阴性(GN)细菌的广谱活性以及其对MDR-GN的“最后手段”剂的重要作用,因此重新考虑了其在临床实践中的使用。尽管用这种古老的抗菌分子治疗具有革命性的观点,关于新的耐药表型特征的出现和粘菌素在临床实践中的最佳使用,许多问题仍然存在。在过去的几年里,在理解阻力决定因素方面已经采取了一些向前的步骤,临床使用,和该分子的药理剂量;然而,关于粘菌素在临床实践中的作用和最佳药代动力学/药效学目标的不同点尚未明确。在这次审查中,我们总结了行动模式,新兴的阻力决定因素,及其在治疗由于MDR革兰氏阴性菌而难以治疗的感染中的最佳给药。