Gibson Gabrielle A, Bauer Seth R, Neuner Elizabeth A, Bass Stephanie N, Lam Simon W
Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio, USA
Department of Pharmacy, Cleveland Clinic, Cleveland, Ohio, USA.
Antimicrob Agents Chemother. 2015 Nov 2;60(1):431-6. doi: 10.1128/AAC.01414-15. Print 2016 Jan.
The increasing prevalence of multidrug-resistant (MDR) nosocomial infections accounts for increased morbidity and mortality of such infections. Infections with MDR Gram-negative isolates are frequently treated with colistin. Based on recent pharmacokinetic studies, current colistin dosing regimens may result in a prolonged time to therapeutic concentrations, leading to suboptimal and delayed effective treatment. In addition, studies have demonstrated an association between an increased colistin dose and improved clinical outcomes. However, the specific dose at which these outcomes are observed is unknown and warrants further investigation. This retrospective study utilized classification and regression tree (CART) analysis to determine the dose of colistin most predictive of global cure at day 7 of therapy. Patients were assigned to high- and low-dose cohorts based on the CART-established breakpoint. The secondary outcomes included microbiologic outcomes, clinical cure, global cure, lengths of intensive care unit (ICU) and hospital stays, and 7- and 28-day mortalities. Additionally, safety outcomes focused on the incidence of nephrotoxicity associated with high-dose colistin therapy. The CART-established breakpoint for high-dose colistin was determined to be >4.4 mg/kg of body weight/day, based on ideal body weight. This study evaluated 127 patients; 45 (35%) received high-dose colistin, and 82 (65%) received low-dose colistin. High-dose colistin was associated with day 7 global cure (40% versus 19.5%; P = 0.013) in bivariate and multivariate analyses (odds ratio [OR] = 3.40; 95% confidence interval [CI], 1.37 to 8.45; P = 0.008). High-dose colistin therapy was also associated with day 7 clinical cure, microbiologic success, and mortality but not with the development of acute kidney injury. We concluded that high-dose colistin (>4.4 mg/kg/day) is independently associated with day 7 global cure.
多重耐药（MDR）医院感染的患病率不断上升，导致此类感染的发病率和死亡率增加。耐多药革兰氏阴性菌感染通常用黏菌素治疗。根据最近的药代动力学研究，目前的黏菌素给药方案可能会导致达到治疗浓度的时间延长，从而导致治疗效果欠佳和延迟有效治疗。此外，研究表明黏菌素剂量增加与临床结果改善之间存在关联。然而，观察到这些结果的具体剂量尚不清楚，值得进一步研究。这项回顾性研究利用分类与回归树（CART）分析来确定在治疗第7天最能预测总体治愈的黏菌素剂量。根据CART确定的断点，将患者分为高剂量组和低剂量组。次要结果包括微生物学结果、临床治愈、总体治愈、重症监护病房（ICU）住院时间和医院住院时间，以及7天和28天死亡率。此外，安全性结果重点关注高剂量黏菌素治疗相关的肾毒性发生率。根据理想体重，CART确定的高剂量黏菌素断点为>4.4mg/kg体重/天。本研究评估了127例患者；45例（35%）接受高剂量黏菌素治疗，82例（65%）接受低剂量黏菌素治疗。在双变量和多变量分析中，高剂量黏菌素与第7天的总体治愈相关（40%对19.5%；P=0.013）（比值比[OR]=3.40；95%置信区间[CI]，1.37至8.45；P=0.008）。高剂量黏菌素治疗还与第7天的临床治愈、微生物学成功和死亡率相关，但与急性肾损伤的发生无关。我们得出结论，高剂量黏菌素（>4.4mg/kg/天）与第7天的总体治愈独立相关。
