Korean-National Institute for Bioprocessing Research and Training (K-NIBRT), Yonsei University, Incheon 21983, the Republic of Korea.
Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, the Republic of Korea.
J Infect Public Health. 2024 May;17(5):843-853. doi: 10.1016/j.jiph.2024.03.021. Epub 2024 Mar 19.
Colistin is a viable option for multidrug resistant gram-negative bacteria emerged from inappropriate antibiotic use. Nonetheless, suboptimal colistin concentrations and nephrotoxicity risks hinder its clinical use. Thus, the aim of this study is to investigate clinical outcomes in correlation with pharmacokinetic differences and infection types in critically ill patients on intravenous colistin methanesulfornate sodium (CMS).
A systematic literature search of Embase, Google Scholars, and PubMed was performed to identify clinical trials evaluating pharmacokinetic parameters along with clinical outcomes of CMS treatment from inception to July 2023. The pooled analyses of clinical impact of CMS on nephrotoxicity, mortality, clinical cure, and colistin concentration at steady state (C) were performed. This study was registered in the PROSPERO (CRD 42023456120).
Total of 695 critically ill patients from 17 studies were included. The mortality was substantially lower in clinically cured patients (OR 0.05; 95% CI 0.02 - 0.14), whereas the mortality rate was statistically insignificant between nephrotoxic and non-nephrotoxic patients. Inter-patient variability of pharmacokinetic parameters of CMS and colistin was observed in critically ill patients. The standard mean differences of C were statistically insignificant between clinically cure and clinically failure groups (standard mean difference (SMD) -0.25; 95% CI -0.69 - 0.19) and between nephrotoxic and non-nephrotoxic groups (SMD 0.67; 95% CI -0.27-1.61). The clinical cure rate is substantially lower in pneumonia patients (OR 0.09; 95% CI 0.01 - 0.56), and pharmacokinetic parameters pertaining to microbiological cure were different among strains.
The mortality rate was substantially lower in clinically cured patients with CMS. However, no significant differences in C of colistin were examined to determine the impact of pharmacokinetic differences on clinical outcomes including mortality rate and nephrotoxicity risk. Nevertheless, the clinical cure rate is substantially lower in patients with respiratory infection than patients with urinary tract infection.
多药耐药革兰氏阴性菌的出现与抗生素的不恰当使用有关，粘菌素是一种可行的选择。然而，粘菌素浓度不理想和肾毒性风险阻碍了其临床应用。因此，本研究旨在探讨与药代动力学差异和感染类型相关的临床结局，以评估重症患者静脉注射粘菌素甲磺酸钠（CMS）的情况。
对 Embase、Google Scholar 和 PubMed 进行了系统的文献检索，以确定从成立到 2023 年 7 月评估 CMS 治疗药代动力学参数与临床结局的临床试验。对 CMS 治疗的肾毒性、死亡率、临床治愈率和稳态时（C）的粘菌素浓度的临床影响进行了汇总分析。本研究已在 PROSPERO（CRD42023456120）注册。
共纳入 17 项研究的 695 例重症患者。在临床治愈的患者中，死亡率明显较低（OR0.05；95%CI0.02-0.14），而在肾毒性和非肾毒性患者中，死亡率无统计学意义。在重症患者中观察到 CMS 药代动力学参数的个体间变异性和粘菌素。在临床治愈和临床失败组之间，C 的标准均数差无统计学意义（标准均数差（SMD）-0.25；95%CI-0.69-0.19）和肾毒性和非肾毒性组之间（SMD0.67；95%CI-0.27-1.61）。在肺炎患者中，临床治愈率明显较低（OR0.09；95%CI0.01-0.56），且不同菌株的微生物学治愈率的药代动力学参数不同。
CMS 治疗的临床治愈患者死亡率明显较低。然而，并未检测到粘菌素 C 的差异对包括死亡率和肾毒性风险在内的临床结局有显著影响。然而，呼吸道感染患者的临床治愈率明显低于尿路感染患者。
