Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Center of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Int J Infect Dis. 2021 May;106:91-97. doi: 10.1016/j.ijid.2021.03.059. Epub 2021 Mar 23.
A colistin loading dose is required to achieve adequate drug exposure for the treatment of multidrug-resistant Gram-negative bacteria. However, data on acute kidney injury (AKI) rates associated with this approach in children have been unavailable. The aim of this study was to examine AKI rates in children who were prescribed a colistin loading dose.
A retrospective study was conducted in patients aged 1 month to 18 years who had received intravenous colistin for ≥48 h. Loading dose (LD) was defined as colistin methanesulfonate at 4-5 mg of colistin base activity/kg/dose. AKI was defined according to KDIGO serum creatinine (SCr) criteria - SCr ≥ 1.5 times the baseline, measured 3-7 days after colistin initiation. Augmented renal clearance (ARC) was defined as an estimated glomerular filtration rate (eGFR) >150 mL/min/1.73 m. The rates of AKI were compared between children receiving or not receiving an LD, and between different eGFR groups.
In total, 181 children were enrolled. The mean age was 4.3 years (95% confidence interval [CI], 3.6-4.9 years). Ninety-five of the subjects (52.5%) were male. There were 157 children with a baseline eGFR of ≥ 80 mL/min/1.73 m. The overall AKI rate within the first week in this group was 20.4% (95% CI, 14.4-27.6%): LD, 16.1% vs no LD, 23.2% (p = 0.29). Subgroup analysis, excluding patients with ARC, showed a lower AKI rate of 12.8% (95% CI, 6.8-21.3%): LD, 9.7% vs no LD, 14.3% (p = 0.53).
AKI rate was not different among children who received an intravenous colistin loading dose. This approach should be implemented to ensure the necessary drug exposure required for good treatment outcomes.
多药耐药革兰氏阴性菌的治疗需要使用粘菌素负荷剂量以达到足够的药物暴露。然而,目前尚无关于儿童应用这种方法后发生急性肾损伤(AKI)的相关数据。本研究旨在探讨接受粘菌素负荷剂量治疗的儿童的 AKI 发生率。
本研究为回顾性研究,纳入了年龄在 1 个月至 18 岁之间、接受静脉用粘菌素治疗时间超过 48 小时的患者。负荷剂量(LD)定义为每公斤体重 4-5 毫克粘菌素甲磺酸盐。AKI 根据 KDIGO 血清肌酐(SCr)标准定义为:粘菌素起始后 3-7 天,SCr 比基线升高 1.5 倍以上。增强的肾清除率(ARC)定义为估计肾小球滤过率(eGFR)>150ml/min/1.73m。比较了接受和未接受 LD 的儿童之间以及不同 eGFR 组之间 AKI 的发生率。
共纳入 181 名儿童,平均年龄为 4.3 岁(95%置信区间[CI]:3.6-4.9 岁),95 名(52.5%)为男性。157 名患儿的基线 eGFR 为≥80ml/min/1.73m。在该组中,第 1 周内 AKI 的总体发生率为 20.4%(95%CI:14.4-27.6%):LD 组为 16.1%,无 LD 组为 23.2%(p=0.29)。排除 ARC 患者的亚组分析显示,AKI 发生率较低为 12.8%(95%CI:6.8-21.3%):LD 组为 9.7%,无 LD 组为 14.3%(p=0.53)。
接受静脉用粘菌素负荷剂量的儿童 AKI 发生率无差异。为了确保良好的治疗效果,应采用这种方法以确保所需的药物暴露。