Ehrentraut Stefan Felix, Muenster Stefan, Kreyer Stefan, Theuerkauf Nils Ulrich, Bode Christian, Steinhagen Folkert, Ehrentraut Heidi, Schewe Jens-Christian, Weber Matthias, Putensen Christian, Muders Thomas
Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany.
MVZ LaborDiagnostik, Am Rüppurrer Schloss 1, 76199 Karlsruhe, Germany.
Microorganisms. 2020 Mar 15;8(3):415. doi: 10.3390/microorganisms8030415.
(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines' recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients.
（1）背景：随着多重/泛耐药（MDR/PDR）病原体的出现，较少使用的抗生素黏菌素再度受到关注。黏菌素曾因治疗窗窄和高毒性风险而失宠。如今，它再次被用作治疗MDR/PDR病原体的最后手段。尽管已有关于黏菌素给药的详细建议的新指南，但在肾衰竭的重症患者中确定合适剂量仍很困难。在此，我们通过对黏菌素进行高分辨率治疗药物监测来评估现行指南建议的有效性。（2）方法：我们采用HPLC-MS/MS方法分析了从8例感染PDR的ICU患者采集的779份样本中黏菌素及其前体药物黏菌素甲磺酸钠（CMS）的血浆水平。评估了肾功能对黏菌素目标水平的影响。（3）结果：CMS水平与黏菌素水平不相关。无论肾功能和肾脏替代治疗方式如何，均出现了用药过量/不足的情况。黏菌素的消除半衰期似乎比先前报道的更长。（4）结论：遵循最新指南的剂量建议不一定能使黏菌素达到足够的血浆水平。在没有治疗药物监测的情况下使用黏菌素可能不安全，且在重症患者中遵循指南并不保证能达到有效的目标水平。
