Luther Megan K, Timbrook Tristan T, Caffrey Aisling R, Dosa David, Lodise Thomas P, LaPlante Kerry L
Rhode Island Infectious Diseases (RIID) Research Program, Veterans Affairs Medical Center, Providence, RI.
University of Rhode Island, College of Pharmacy, Kingston, RI.
Crit Care Med. 2018 Jan;46(1):12-20. doi: 10.1097/CCM.0000000000002769.
The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy.
Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched.
Articles not in English, pediatric studies, and case reports were excluded.
Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3.
Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, -1.30; 95% CI, -3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57-4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83-3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97-3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48-20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83-2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86-2.11).
The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed.
本系统评价和荟萃分析的目的是评估万古霉素联合哌拉西林 - 他唑巴坦治疗对普通成年患者和重症成年患者急性肾损伤的影响。将急性肾损伤的发生率、发生急性肾损伤的时间以及急性肾损伤的比值比与万古霉素单药治疗、万古霉素联合头孢吡肟或碳青霉烯类药物治疗，或哌拉西林 - 他唑巴坦单药治疗进行比较。
通过检索PubMed、Embase、Web of Science和Cochrane数据库，从建库至2017年4月来识别研究。对所选会议论文集的摘要进行手动检索。
排除非英文文章、儿科研究和病例报告。
两位作者独立提取关于研究方法、急性肾损伤发生率和发生急性肾损伤时间的数据。使用RevMan 5.3中的随机效应模型计算效应估计值和95%置信区间。
文献检索确定了15篇已发表研究和17篇会议摘要，涉及至少24,799例患者。急性肾损伤的总体发生率为16.7%，万古霉素联合哌拉西林 - 他唑巴坦治疗组为22.2%，对照治疗组为12.9%。这得出总体伤害所需人数为11。万古霉素联合哌拉西林 - 他唑巴坦治疗发生急性肾损伤的时间比万古霉素联合头孢吡肟或碳青霉烯类药物治疗更快，但差异无统计学意义（平均差值，-1.30；95%置信区间，-3.00至0.41天）。与万古霉素单药治疗相比（比值比，3.40；95%置信区间，2.57 - 4.50）、与万古霉素联合头孢吡肟或碳青霉烯类药物治疗相比（比值比，2.68；95%置信区间，1.83 - 3.91）以及与哌拉西林 - 他唑巴坦单药治疗相比（比值比，2.70；95%置信区间，1.97 - 3.69），万古霉素联合哌拉西林 - 他唑巴坦治疗发生急性肾损伤的比值比均升高。在对968例重症患者的一项小型亚组分析中，与万古霉素单药治疗相比，急性肾损伤的比值比升高（比值比，9.62；95%置信区间，4.48 - 20.68），但与万古霉素联合头孢吡肟或碳青霉烯类药物治疗（比值比，1.43；95%置信区间，0.83 - 2.47）或哌拉西林 - 他唑巴坦单药治疗（比值比，1.35；95%置信区间，0.86 - 2.11）相比，差异无统计学意义。
与万古霉素单药治疗、万古霉素联合头孢吡肟或碳青霉烯类药物治疗以及哌拉西林 - 他唑巴坦单药治疗相比，万古霉素联合哌拉西林 - 他唑巴坦治疗增加了急性肾损伤的比值比。重症患者的有限数据表明，与万古霉素单药治疗相比，急性肾损伤的比值比升高，而与其他对照治疗相比则降低。需要对重症患者群体进行进一步研究。
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