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

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 piperacillin-tazobactam 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 minimum 1.5 fold increase in serum creatinine concentration. Results Nephrotoxicity developed in 15 (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.