Laboratory of Experimental Surgery and Surgical Research N.S. Christeas, Athens University Medical School, National and Kapodistrian University of Athens, Athens, Greece.
First Department of Obstetrics and Gynaecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
J Antimicrob Chemother. 2020 Jul 1;75(7):1689-1698. doi: 10.1093/jac/dkaa064.
Colistin represents a polypeptide used for the treatment of MDR microorganisms, although the optimal dosing strategy is under investigation. The present meta-analysis aims to determine whether the administration of a colistin loading dose in patients receiving high-dose maintenance regimens changes the rates of treatment success and the risk of nephrotoxicity.
Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from inception to 18 November 2019. Studies were considered eligible if they reported clinical outcomes among patients receiving high-dose colistin therapy with and without the administration of a loading dose. Meta-analysis was performed by fitting a random-effects model.
Eight (three prospective and five retrospective cohort) studies were included, comprising 1115 patients. The administration of a colistin loading dose was associated with significantly higher microbiological [risk ratio (RR) = 1.23, 95% CI = 1.10-1.39] but not clinical (RR = 1.04, 95% CI = 0.87-1.24) success. No significant associations were calculated for nephrotoxicity (RR = 1.31, 95% CI = 0.90-1.91) and mortality (RR = 1.03, 95% CI = 0.82-1.29) risk. The results remained stable after adjustments for small sample size, credibility ceilings, publication bias and risk of bias.
Observational evidence suggests that the administration of a colistin loading dose in patients receiving high maintenance dosage regimens is significantly associated with higher rates of microbiological response, but does not change clinical cure, mortality or nephrotoxicity risk. The dosing regimen that would provide the optimal balance between treatment efficacy and safety needs to be determined by future randomized controlled trials.
多黏菌素是一种用于治疗耐多药微生物的多肽药物，但其最佳给药方案仍在研究中。本荟萃分析旨在确定在接受高剂量维持治疗方案的患者中给予多黏菌素负荷剂量是否会改变治疗成功率和肾毒性风险。
系统检索了 Medline、Scopus、CENTRAL、Clinicaltrials.gov 和 Google Scholar 从建库到 2019 年 11 月 18 日的数据。如果研究报告了接受高剂量多黏菌素治疗的患者中有无负荷剂量给药的临床结局，则认为其符合纳入标准。采用随机效应模型进行荟萃分析。
共纳入 8 项（3 项前瞻性研究和 5 项回顾性队列研究）研究，共纳入 1115 例患者。给予多黏菌素负荷剂量与微生物学成功率显著提高相关[风险比（RR）=1.23，95%可信区间（CI）=1.10-1.39]，但与临床成功率无关（RR=1.04，95%CI=0.87-1.24）。未发现肾毒性（RR=1.31，95%CI=0.90-1.91）和死亡率（RR=1.03，95%CI=0.82-1.29）风险存在显著相关性。在对小样本量、可信度上限、发表偏倚和偏倚风险进行调整后，结果仍然稳定。
观察性证据表明，在接受高维持剂量方案治疗的患者中给予多黏菌素负荷剂量与更高的微生物学反应率显著相关，但不会改变临床治愈率、死亡率或肾毒性风险。需要进一步的随机对照试验来确定在治疗效果和安全性之间提供最佳平衡的给药方案。
