Rutter W Cliff, Burgess Donna R, Talbert Jeffery C, Burgess David S
University of Kentucky College of Pharmacy, Lexington, KY, USA.
University of Kentucky HealthCare, Lexington, KY, USA.
J Hosp Med. 2017 Feb;12(2):77-82. doi: 10.12788/jhm.2684.
Empiric antimicrobial therapy often consists of the combination of gram-positive coverage with vancomycin (VAN) and gram-negative coverage, specifically an antipseudomonal beta-lactam such as piperacillin-tazobactam (PTZ). Nephrotoxicity is commonly associated with VAN therapy; however, recent reports show higher nephrotoxicity rates among patients treated with the combination of VAN and PTZ.
This study evaluated the effect of the VAN/PTZ combination on acute kidney injury (AKI) compared to VAN and PTZ monotherapies.
DESIGN, SETTING, AND PATIENTS: This is a retrospective cohort analysis of adult patients without renal disease receiving VAN, PTZ, or the combination from September 1, 2010 through August 31, 2014 at an academic medical center.
The primary outcome was AKI incidence as defined by the Risk, Injury, Failure, Loss, End-stage (RIFLE) criteria.
Continuous and categorical variables were assessed with appropriate tests. Univariate and multivariate logistic regressions were performed to assess for associations between variables and AKI incidence. Subanalyses based on severity of illness were performed.
Overall, 11,650 patients were analyzed, with 1647 (14.1%) developing AKI. AKI was significantly more frequent in the VAN/PTZ group (21%) compared to either monotherapy group (VAN 8.3%, PTZ 7.8%, P ⟨ 0.001 for both). Combination therapy was independently associated with higher AKI odds compared to monotherapy with either agent (adjusted odds ratio [aOR], 2.03; 95% confidence interval [CI], 1.74-2.39; aOR, 2.31; 95% CI, 1.97-2.71, for VAN and PTZ, respectively). Receipt of concomitant nephrotoxic drugs was independently associated with increased AKI rates, as were increased duration of therapy, hospital length of stay, increasing severity of illness, and increasing baseline renal function.
In this study of more than 10,000 patients, VAN combined with PTZ was associated with twice the odds of AKI development compared to either agent as monotherapy. This demonstrates the need for judicious use of combination empiric therapy. Journal of Hospital Medicine 2017;12:77-82.
经验性抗菌治疗通常包括用万古霉素（VAN）覆盖革兰氏阳性菌和用抗假单胞菌β-内酰胺类药物（如哌拉西林-他唑巴坦（PTZ））覆盖革兰氏阴性菌。肾毒性通常与万古霉素治疗相关；然而，最近的报告显示，接受万古霉素和哌拉西林-他唑巴坦联合治疗的患者中肾毒性发生率更高。
本研究评估了万古霉素/哌拉西林-他唑巴坦联合治疗与万古霉素和哌拉西林-他唑巴坦单药治疗相比对急性肾损伤（AKI）的影响。
设计、地点和患者：这是一项对2010年9月1日至2014年8月31日在一家学术医疗中心接受万古霉素、哌拉西林-他唑巴坦或联合治疗的无肾脏疾病成年患者的回顾性队列分析。
主要结局是根据风险、损伤、衰竭、丧失、终末期（RIFLE）标准定义的急性肾损伤发生率。
使用适当的检验评估连续变量和分类变量。进行单变量和多变量逻辑回归以评估变量与急性肾损伤发生率之间的关联。基于疾病严重程度进行亚组分析。
总体而言，分析了11650例患者，其中1647例（14.1%）发生急性肾损伤。与任何一种单药治疗组相比，万古霉素/哌拉西林-他唑巴坦组的急性肾损伤发生率显著更高（21%）（万古霉素组为8.3%，哌拉西林-他唑巴坦组为7.8%，两者P均<0.001）。与任何一种药物的单药治疗相比，联合治疗与更高的急性肾损伤几率独立相关（调整后的优势比[aOR]，2.03；95%置信区间[CI]，1.74 - 2.39；万古霉素和哌拉西林-他唑巴坦的aOR分别为2.31；95% CI，1.97 - 2.71）。接受伴随的肾毒性药物与急性肾损伤发生率增加独立相关，治疗持续时间增加、住院时间延长、疾病严重程度增加以及基线肾功能增加也与急性肾损伤发生率增加相关。
在这项对10000多名患者的研究中，与任何一种药物单药治疗相比，万古霉素联合哌拉西林-他唑巴坦发生急性肾损伤的几率高出两倍。这表明需要谨慎使用联合经验性治疗。《医院医学杂志》2017年；12：77 - 82。
