Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children
Association of Acute Kidney Injury With Concomitant Vancomycin and Piperacillin/Tazobactam Treatment Among Hospitalized Children
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DOI：
10.1001/jamapediatrics.2017.3219
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发表时间：
2017-12-01
期刊：
影响因子：
26.1
通讯作者：
Zaoutis, Theoklis E.
中科院分区：
文献类型：
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作者：
Downes, Kevin J.;Cowden, Carter;Zaoutis, Theoklis E.
重要性 对于疑似严重感染的儿童，β-内酰胺抗生素通常与静脉注射 (IV) 盐酸万古霉素联合给药。对于成人来说，与万古霉素加 1 种其他 β-内酰胺抗生素相比，静脉注射万古霉素加哌拉西林钠/他唑巴坦钠的组合会增加急性肾损伤 (AKI) 的风险。然而，很少有研究评估这种组合对儿童的安全性。 目的 评估儿童在住院第一周内接受万古霉素和 1 种抗假单胞菌 β-内酰胺抗生素联合治疗期间发生 AKI 的风险。 设计、环境和参与者 这项回顾性队列研究的重点是住院 3 天或以上且接受静脉注射万古霉素加 1 种其他抗假单胞菌药物的儿童。 从2007年1月1日到2012年12月31日，在6家大型儿童医院中的1家进行了β-内酰胺联合治疗。该研究使用了儿科健康信息系统Plus数据库，其中包含来自美国6家儿科医院的管理和实验室数据。患有潜在肾脏疾病或住院第 0 至 2 天血清肌酐水平异常的患者被排除在外。包括通过医院急诊科入院的6个月至18岁的患者。数据收集时间为 2015 年 7 月至 2016 年 3 月。数据分析时间为 2016 年 4 月至 2017 年 7 月。（由于数据收集和分析过程是迭代的，因此无法提供确切日期。） 主要结果和措施 主要结果是住院第 3 至 7 天以及接受联合治疗后 2 天内发生 AKI。使用 KDIGO 标准定义急性肾损伤，并基于住院第 0 至 2 天到住院第 3 至 7 天的血清肌酐水平变化。使用离散时间失败模型进行多重逻辑回归，以测试 AKI 与静脉注射万古霉素加哌拉西林/他唑巴坦或万古霉素加 1 种其他抗假单胞菌 β-内酰胺抗生素之间的关联。 确定了 1915 名接受联合治疗的住院儿童。在 1915 名患者中，共有 866 名患者（45.2%）为女性，1049 名患者（54.8%）为男性，1049 名患者（54.8%）在种族/族裔上被确定为白人，中位年龄（四分位距）为 5.6（2.1-12.7）岁。在接受静脉注射万古霉素加 1 种其他抗假单胞菌 β-内酰胺抗生素的队列中，157 名患者 (8.2%) 患有抗生素相关 AKI。这一数字包括 1009 名接受静脉注射万古霉素加哌拉西林/他唑巴坦联合治疗的患者中的 117 名 (11.7%)。调整年龄、重症监护病房护理水平、肾毒素接受情况和医院后，与万古霉素加 1 种其他抗假单胞菌 β-内酰胺抗生素组合相比，静脉注射万古霉素加哌拉西林/他唑巴坦联合治疗与每个住院日发生 AKI 的几率较高相关（调整后的比值比为 3.40；95% CI， 2.26-5.14).结论和相关性静脉注射万古霉素和哌拉西林/他唑巴坦的共同给药可能会增加住院儿童发生 AKI 的风险。儿科医生在做出经验性抗生素选择时必须认识到这种联合疗法潜在的额外风险。
IMPORTANCE beta-Lactam antibiotics are often coadministered with intravenous (IV) vancomycin hydrochloride for children with suspected serious infections. For adults, the combination of IV vancomycin plus piperacillin sodium/tazobactam sodium is associated with a higher risk of acute kidney injury (AKI) compared with vancomycin plus 1 other beta-lactam antibiotic. However, few studies have evaluated the safety of this combination for children.OBJECTIVE To assess the risk of AKI in children during concomitant therapy with vancomycin and 1 antipseudomonal beta-lactam antibiotic throughout the first week of hospitalization.DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study focused on children hospitalized for 3 or more days who received IV vancomycin plus 1 other antipseudomonal beta-lactam combination therapy at 1 of 6 large children's hospitals from January 1, 2007, through December 31, 2012. The study used the Pediatric Health Information System Plus database, which contains administrative and laboratory data from 6 pediatric hospitals in the United States. Patients with underlying kidney disease or abnormal serum creatinine levels on hospital days 0 to 2 were among those excluded. Patients 6 months to 18 years of age who were admitted through the emergency department of the hospital were included. Data were collected from July 2015 to March 2016. Data analysis took place from April 2016 through July 2017. (Exact dates are not available because the data collection and analysis processes were iterative.)MAIN OUTCOMES AND MEASURES The primary outcome was AKI on hospital days 3 to 7 and within 2 days of receiving combination therapy. Acute kidney injury was defined using KDIGO criteria and was based on changes in serum creatinine level from hospital days 0 to 2 through hospital days 3 to 7. Multiple logistic regression was performed using a discrete-time failure model to test the association between AKI and receipt of IV vancomycin plus piperacillin/tazobactam or vancomycin plus 1 other antipseudomonal beta-lactam antibiotic.RESULTS A total of 1915 hospitalized children who received combination therapy were identified. Of the 1915 patients, a total of 866 (45.2%) were female and 1049 (54.8%) were male, 1049 (54.8%) were identified as white in race/ethnicity, and the median (interquartile range) age was 5.6 (2.1-12.7) years. Among the cohort who received IV vancomycin plus 1 other antipseudomonal beta-lactam antibiotic, 157 patients (8.2%) had antibiotic-associated AKI. This number included 117 of 1009 patients (11.7%) who received IV vancomycin plus piperacillin/tazobactam combination therapy. After adjustment for age, intensive care unit level of care, receipt of nephrotoxins, and hospital, IV vancomycin plus piperacillin/tazobactam combination therapy was associated with higher odds of AKI each hospital day compared with vancomycin plus 1 other antipseudomonal beta-lactam antibiotic combination (adjusted odds ratio, 3.40; 95% CI, 2.26-5.14).CONCLUSIONS AND RELEVANCE Coadministration of IV vancomycin and piperacillin/tazobactam may increase the risk of AKI in hospitalized children. Pediatricians must be cognizant of the potential added risk of this combination therapy when making empirical antibiotic choices.