住院儿童单独使用万古霉素或联合哌拉西林/他唑巴坦治疗后的肾毒性比较

Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized children with or without concomitant piperacillin-tazobactam

目的探讨哌拉西林/他唑巴坦（piperacillin-tazobactam,PLTZ）联合应用万古霉素（vancomycin,VAN）在儿童中是否会导致肾毒性的发生率增加,及其他可能增加肾毒性的混杂危险因素。方法收集2004年1月1日至2014年12月31日之间在复旦大学附属儿科医院住院治疗的250例患儿,采用单中心、回顾性队列研究。治疗前肾功能正常并接受至少48 h的VAN治疗的患儿被纳入分析。其中125例患儿接受至少48 h的PLTZ联合VAN静脉滴注（联合组）,余125例接受VAN治疗（VAN组）。对肌酐和尿素氮等检验数据和主要结果进行单因素分析,评估联合用药的风险因素对治疗后7天内肾毒性发病率的影响。其中,肾毒性的主要终点定义为血清肌酐浓度至少增长1.5倍。结果共有250例患儿纳入研究,其中有125例同时接受至少48 h静脉滴注PLTZ与VAN（联合用药组）治疗,另外共有125例接受VAN和头孢吡肟而不接受PLTZ治疗（单纯VAN组）。联合用药组肾毒性发生率为48.8%（61/125）,单纯VAN组为12.0%（15/125）。与单纯VAN治疗相比,PLTZ与VAN联合治疗显示肾毒性的发生率增加6.99倍（OR=6.99,95%CI=3.67-13.30,P=0.001）。结论VAN联合PLTZ治疗可以显著增加患儿的肾毒性发生率。与成人的研究结果相比,儿童中联用VAN与PLTZ可能存在更高的风险。

Objective To determine whether the addition of piperacillin-tazobactam lead to an increased incidence of nephrotoxicity in children receiving vancomycin and to explore potential confounding factors that may increase the risk of vancomycin-induced nephrotoxicity. Methods A single-center,retrospective cohort study was carried out in Children′s Hospital of Fudan University.Two hundred and fifty children hospitalized with normal baseline renal function between Jan.1,2004 and Dec.31,2014,who received a minimum of 48 hours of vancomycin for any indication were included in the analysis.Of these patients,125 received aminimum of 48 hours of intravenous piperacillintazobactam concurrently with vancomycin（combination group）;125 received vancomycin without piperacillin-tazobactam（vancomycin group）.Single factor analysis was performed to assess the effect of the risk factors on the incidence of nephrotoxicity within the first 7 days of vancomycin treatment,based on creatinine and urea nitrogen level.The primary end point of nephrotoxicity was defined as a minimum1.5 fold increase in serum creatinine concentration. Results Nephrotoxicity developed in15（12.0%）of 125 patients in the vancomycin group and in 61（48.8%）of 125 patients in the combination group（P=0.001）.Patients with piperacillin-tazobactam added to vancomycin exhibited an increased incidence of nephrotoxicity,with an odds ratio of 6.99（OR=6.99,95%CI=3.67-13.30）.Conclusions We observed an increased incidence of nephrotoxicity in vancomycin-treated patients who received concomitant piperacillin-tazobactam.Compared with adult,there may be a higher risk in children treated with vancomycin and piperacillin-tazobactam.