Yasrebi-de Kom Izak A R, Jager Kitty J, Stel Vianda S, Chesnaye Nicholas C, Abu-Hanna Ameen, de Keizer Nicolette F, de Lange Dylan W, Dongelmans Dave A, Klopotowska Joanna E, Cinà Giovanni
Department of Medical Informatics, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Amsterdam Public Health, Amsterdam, the Netherlands.
Pharmacoepidemiol Drug Saf. 2025 Sep;34(9):e70205. doi: 10.1002/pds.70205.
The potential of vancomycin to cause acute kidney injury (AKI) in adult intensive care patients is subject to debate due to suboptimal designs of past studies. Therefore, we aimed to estimate the effect of initiating vancomycin versus one of several minimally nephrotoxic alternative antibiotics on the 14-day risk of AKI using the target trial emulation framework.
A hypothetical trial was emulated using routinely collected data from 15 Dutch intensive care units (ICUs) spanning 2010-2019. We used an active comparator control group with the following alternative antibiotics: clindamycin, linezolid, teicoplanin, meropenem, cefazolin, and daptomycin. AKI was diagnosed according to the KDIGO serum creatinine (SCr) criteria. Cumulative incidence curves were estimated using the Aalen-Johansen method and adjusted for confounding and selection bias through inverse probability of treatment and censoring weighting. Given the time lag of 24-48 h between changes in renal function and SCr, we summarized the estimates by calculating the absolute risks and risk differences at both 2 and 14 days after initiation.
We included 1809 ICU admissions. After adjustment, vancomycin was associated with a higher risk of AKI at 14 days of follow-up compared to the alternative antibiotics (0.28 [95% confidence interval (CI) 0.21-0.34] vs. 0.17 [95% CI 0.14-0.20]; risk difference 0.11 [95% CI 0.04-0.19]), but not at 2 days of follow-up (0.10 [95% CI 0.06-0.12] vs. 0.10 [95% CI 0.08-0.11]; risk difference 0.00 [95% CI -0.03-0.03]).
Our findings indicate that vancomycin causes a higher risk of AKI compared to the alternative antibiotics. We recommend clinicians to be compliant with vancomycin-induced AKI prevention strategies, such as therapeutic drug monitoring or the consideration of an alternative antibiotic if possible.
由于既往研究设计存在缺陷，万古霉素在成年重症监护患者中导致急性肾损伤（AKI）的可能性存在争议。因此，我们旨在使用目标试验模拟框架，评估起始使用万古霉素与几种肾毒性最小的替代抗生素之一相比，对AKI 14天风险的影响。
使用2010年至2019年期间从15家荷兰重症监护病房（ICU）常规收集的数据模拟一项假设试验。我们使用了一个活性对照对照组，其中包括以下替代抗生素：克林霉素、利奈唑胺、替考拉宁、美罗培南、头孢唑林和达托霉素。根据KDIGO血清肌酐（SCr）标准诊断AKI。使用Aalen-Johansen方法估计累积发病率曲线，并通过治疗逆概率和删失加权对混杂因素和选择偏倚进行校正。鉴于肾功能变化与SCr之间存在24 - 48小时的时间滞后，我们通过计算起始后2天和14天的绝对风险和风险差异来总结估计值。
我们纳入了1809例ICU入院患者。调整后，与替代抗生素相比，万古霉素在随访14天时与更高的AKI风险相关（0.28 [95%置信区间（CI）0.21 - 0.34] 对 0.17 [95% CI 0.14 - 0.20]；风险差异0.11 [95% CI 0.04 - 0.19]），但在随访2天时并非如此（0.10 [95% CI 0.06 - 0.12] 对 0.10 [95% CI 0.08 - 0.11]；风险差异0.00 [95% CI -0.03 - 0.03]）。
我们的研究结果表明，与替代抗生素相比，万古霉素导致AKI的风险更高。我们建议临床医生遵守万古霉素诱导的AKI预防策略，如治疗药物监测或尽可能考虑使用替代抗生素。
