The aim of this study was to assess the clinical and microbiological efficacy and toxicity of different high-dose regimens of colistin in the ICU patients with colistin-sensitive MDR Gram-negative infections. In this prospective, open label, randomized clinical trial, patients with clinical features of infection and positive culture for MDR colistin-sensitive Gram-negative bacteria were randomly allocated to receive colistin, 3 or 9 million units every 8 and 24 hours, (groups A and B), respectively. For each dose regimen, clinical and microbiological response, the rates of nephrotoxicity, and its risk factors were analyzed. Forty-three patients were enrolled, and 35 completed the study protocol, of whom 30 (88.2%) had ventilator-associated pneumonia (VAP) and 5 (14%) had bacteremia. Although there were no statistically significant differences in the clinical or microbiological response between the study groups, the microbiological response favored the divided dose group numerically (). Clinical response was achieved in 27 of 35 (77.1%) patients (). Twelve (34.28%) patients developed AKI during colistin treatment, 4 and 8 in groups A and B, respectively ( value =0.193). Significant risk factors for nephrotoxicity related to colistin were age, hyperbilirubinemia, and coadministration of other nephrotoxic agents. In multivariate regression analysis, the only independent risk factor for CMS-associated AKI was hyperbilirubinemia ( value =0.008). Although the clinical and microbiological responses to colistin administration were not statistically different in two groups, the microbiological response favored the divided dose regimen group numerically. We did not observe any significant safety concerns with high-dose colistin administration in this population.

中文翻译：

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对ICU中多药耐药革兰氏阴性感染进行高剂量colistin管理的比较研究

这项研究的目的是评估大肠菌素敏感的MDR革兰氏阴性感染的ICU患者中不同剂量的大肠菌素的临床和微生物学疗效以及毒性。在这项前瞻性，开放标签，随机临床试验中，将具有感染临床特征且MDR大肠粘菌素敏感的革兰氏阴性菌培养阳性的患者随机分配为每8和24小时3或900万单位接受大粘菌素（A组和B）。对于每种剂量方案，临床和微生物反应，肾毒性发生率及其危险因素均进行了分析。招募了43位患者，其中35位完成了研究方案，其中30位（88.2％）患有呼吸机相关性肺炎（VAP），而5位（14％）患有菌血症。）。35例患者中有27例（77.1％）达到了临床反应（）。在粘菌素治疗期间有十二名（34.28％）患者发生AKI，A组和B组分别为4名和8名（值= 0.193）。与大肠菌素相关的肾毒性的重要危险因素是年龄，高胆红素血症和其他肾毒性药物的共同给药。在多元回归分析中，与CMS相关的AKI的唯一独立危险因素是高胆红素血症（值= 0.008）。尽管两组对粘菌素的临床反应和微生物反应在统计学上均无统计学差异，但从数字上看，微生物反应有利于分剂量方案组。在该人群中，大剂量粘菌素的给药没有发现任何重大的安全隐患。