Landersdorfer Cornelia B, Nation Roger L
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
Semin Respir Crit Care Med. 2015 Feb;36(1):126-35. doi: 10.1055/s-0034-1398390. Epub 2015 Feb 2.
Colistin, an "old" polymyxin antibiotic, is increasingly being used as last-line treatment against infections caused by multidrug-resistant gram-negative bacteria. It is administered in patients, parenterally or by inhalation, as its inactive prodrug colistin methanesulfonate (CMS). Scientifically based recommendations on how to optimally dose colistin in critically ill patients have become available over the last decade and are extremely important as colistin has a narrow therapeutic window. A dosing algorithm has been developed to achieve desired plasma colistin concentrations in critically ill patients. This includes the necessary dose adjustments for patients with impaired kidney function and those on renal replacement therapy. Due to the slow conversion of CMS to colistin, a loading dose is needed to generate effective concentrations within a reasonable time period. Therapeutic drug monitoring is warranted, where available; because of the observed high interpatient variability in plasma colistin concentrations. Combination therapy should be considered when the infecting pathogen has a colistin minimum inhibitory concentration above 1 mg/L, as increasing the dose may not be feasible due to the risk for nephrotoxicity. Inhalation of CMS achieves considerably higher colistin concentrations in lung fluids than is possible with intravenous administration, with negligible plasma exposure. Similarly, for central nervous system infections, dosing CMS directly into the cerebrospinal fluid generates significantly higher colistin concentrations at the infection site compared with what can be achieved with systemic administration. While questions remain to be addressed via ongoing research, this article reviews the significant advances that have been made toward optimizing the clinical use of colistin.
黏菌素，一种“老”的多黏菌素类抗生素，正越来越多地被用作治疗多重耐药革兰氏阴性菌感染的最后一线药物。它以其无活性前体药物黏菌素甲磺酸盐（CMS）的形式，通过静脉注射或吸入的方式用于患者。在过去十年中，关于如何在重症患者中最佳地使用黏菌素进行给药的科学建议已经出台，由于黏菌素的治疗窗较窄，这些建议极为重要。已经开发出一种给药算法，以在重症患者中达到所需的血浆黏菌素浓度。这包括对肾功能受损患者和接受肾脏替代治疗患者的必要剂量调整。由于CMS向黏菌素的转化缓慢，需要给予负荷剂量以在合理时间内产生有效浓度。在可行的情况下，应进行治疗药物监测；因为观察到血浆黏菌素浓度在患者之间存在很大差异。当感染病原体的黏菌素最低抑菌浓度高于1mg/L时，应考虑联合治疗，因为由于存在肾毒性风险，增加剂量可能不可行。吸入CMS在肺液中达到的黏菌素浓度比静脉给药所能达到的浓度高得多，而血浆暴露可忽略不计。同样，对于中枢神经系统感染，与全身给药相比，将CMS直接注入脑脊液在感染部位产生的黏菌素浓度明显更高。虽然仍有一些问题有待通过正在进行的研究来解决，但本文回顾了在优化黏菌素临床应用方面取得的重大进展。
