Department of Nephrology, Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University), Nanjing, China.
Department of Nephrology, Jiangsu Province Hospital (The First Affiliated Hospital of Nanjing Medical University), Nanjing, China.
Clin Ther. 2021 Oct;43(10):e319-e351. doi: 10.1016/j.clinthera.2021.08.008. Epub 2021 Sep 25.
The combination of vancomycin and piperacillin/tazobactam (VAN + PTZ) provides a broad spectrum of activity against multiple pathogens. However, a major issue in previous research concerned significant nephrotoxicity associated with this drug combination, and most studies have been conducted in American and European countries, with no similar data available from China. Therefore, this study evaluated the nephrotoxic effects of VAN + PTZ in a large-scale Chinese cohort to determine the prevalence of acute kidney injury (AKI) in this population by comparing PTZ and vancomycin monotherapies and the combined use of vancomycin and β-lactam antibiotics.
This retrospective cohort study identified adult patients who received vancomycin either as monotherapy or in combination with PTZ or carbapenem (VAN + CAR) for at least 48 hours at Jiangsu Province Hospital from January 1, 2017, to December 31, 2018. Patients were also evaluated for the development of AKI, defined according to the Kidney Disease Improving Global Outcome criteria. Duration of vancomycin exposure, steady-state trough vancomycin concentrations, and other risk factors for AKI were assessed. A Bayesian network meta-analysis was conducted to validate our results and comparatively evaluate the nephrotoxicity of β-lactam antibiotics in combination with vancomycin.
In all, 752 patients were included in the present study. The prevalence of AKI was higher in the VAN + PTZ group than in the VAN and VAN + CAR groups (15.2% vs 4.0% and 6.0%, respectively). After adjustment for confounding factors, VAN + PTZ was still related to AKI (odds ratio [OR] = 4.37; 95% CI, 1.65-11.59; P = 0.003). The network meta-analysis indicated that VAN + PTZ was associated with a significantly higher risk for AKI than was VAN (OR = 3.23; 95% CI, 2.50-4.35), PTZ (OR = 2.86; 95% CI, 1.92-4.12), VAN + cefepime (FEP) (OR = 2.37; 95% CI, 1.80-3.19), or VAN + CAR (OR = 2.28; 95% CI, 1.64-3.21). However, there was no significant difference with respect to AKI prevalence among the VAN, PTZ, VAN + FEP, and VAN + CAR groups.
The prevalence of AKI was higher with VAN + PTZ therapy than with VAN or PTZ monotherapy or with the concurrent use of VAN and FEP or CAR in our study. Clinicians should adequately assess renal function and consider this differential risk for nephrotoxicity when choosing empiric antibiotics in hospitalized patients to minimize the rates of AKI.
万古霉素和哌拉西林/他唑巴坦(VAN+PTZ)联合使用具有针对多种病原体的广谱活性。然而,以往研究中的一个主要问题是该药物联合使用会导致明显的肾毒性,并且大多数研究都在美国和欧洲进行,中国没有类似的数据。因此,本研究评估了 VAN+PTZ 在大规模中国队列中的肾毒性作用,通过比较 PTZ 和万古霉素单药治疗以及万古霉素和β-内酰胺类抗生素联合使用,来确定该人群中急性肾损伤(AKI)的患病率。
本回顾性队列研究纳入了 2017 年 1 月 1 日至 2018 年 12 月 31 日期间在江苏省人民医院至少接受万古霉素单药或与 PTZ 或碳青霉烯类(VAN+CAR)联合治疗 48 小时以上的成年患者。根据肾脏疾病改善全球结局(KDIGO)标准评估 AKI 的发生情况。评估了万古霉素暴露时间、稳态谷浓度和其他 AKI 风险因素。进行了贝叶斯网络荟萃分析以验证我们的结果,并比较评估了与万古霉素联合使用的β-内酰胺类抗生素的肾毒性。
本研究共纳入 752 例患者。VAN+PTZ 组 AKI 患病率高于 VAN 组和 VAN+CAR 组(15.2%比 4.0%和 6.0%)。调整混杂因素后,VAN+PTZ 仍与 AKI 相关(比值比[OR]为 4.37;95%置信区间,1.65-11.59;P=0.003)。网络荟萃分析表明,VAN+PTZ 与 AKI 的风险显著高于 VAN(OR=3.23;95%置信区间,2.50-4.35)、PTZ(OR=2.86;95%置信区间,1.92-4.12)、VAN+头孢吡肟(FEP)(OR=2.37;95%置信区间,1.80-3.19)或 VAN+CAR(OR=2.28;95%置信区间,1.64-3.21)。然而,VAN、PTZ、VAN+FEP 和 VAN+CAR 组之间 AKI 患病率无显著差异。
与 VAN 单药治疗或 PTZ 单药治疗或与 VAN 和 FEP 或 CAR 同时使用相比,VAN+PTZ 治疗的 AKI 患病率更高。临床医生在选择经验性抗生素治疗住院患者时应充分评估肾功能,并考虑这种肾毒性的差异风险,以尽量降低 AKI 的发生率。