Zamoner Welder, Gonçalves Pierri Isabella, Zanchetta Cardoso Eid Karina, Maria Bellaver de Almeida Lais, Dos Santos Adriano, Luís Balbi André, Ponce Daniela
Botucatu School of Medicine, São Paulo State University - UNESP, Botucatu, São Paulo, Brazil.
Clinics Hospital Pharmacy, Botucatu School of Medicine, Botucatu, São Paulo 18618-970, Brazil.
Infect Drug Resist. 2020 Feb 10;13:403-411. doi: 10.2147/IDR.S219989. eCollection 2020.
There have been few studies to evaluate the monitoring of plasmatic concentrations of vancomycin in septic patients and their association with acute kidney injury (AKI) and death. This study aimed to evaluate the prevalence of adequate, subtherapeutic, and toxic serum concentrations of vancomycin in hospitalized septic patients and to associate the adequacy of therapeutic monitoring with clinical outcomes.
This was a cohort-unicentric study that evaluated septic patients aged >18 years using vancomycin admitted to clinical and surgical wards of a Brazilian university center from August 2016 to July 2017 in a daily and uninterrupted way. We excluded patients with AKI prior to the introduction of vancomycin or with AKI development <48 hours after use, patients with AKI of other etiologies, stage V chronic kidney disease, and pregnant women.
We evaluated 225 patients, and 135 were included. Evaluation of serum concentration of vancomycin was realized in 94.1%, and of those, 59.3% presented toxic concentrations. The prevalence of AKI was 27.4% and happened on average on the ninth day of vancomycin usage. Between the fourth and sixth days, vancomycin serum concentration of >21.5 mg/L was a predictor of AKI, with area under the curve of 0.803 (95% CI 0.62-0.98, =0.005), preceding the diagnosis of AKI by at least 3 days. Of these patients, 20.7% died, and serum concentrations of vancomycin between the fourth and sixth days were identified as risk factors associated with negative outcomes.
Serum concentration of vancomycin is an excellent predictor of AKI in patients admitted to wards, preceding the diagnosis of AKI by at least 72 hours. Toxic concentrations of vancomycin are associated with AKI, and AKI was a risk factor for death. Also, serum concentration of vancomycin >21.5 mg/L was the only variable associated with death in the Cox model.
很少有研究评估脓毒症患者万古霉素血药浓度监测及其与急性肾损伤（AKI）和死亡的关联。本研究旨在评估住院脓毒症患者万古霉素血清浓度达到适宜、亚治疗水平及中毒水平的发生率，并探讨治疗监测的充分性与临床结局的关系。
这是一项单中心队列研究，对2016年8月至2017年7月期间在巴西某大学中心临床和外科病房每日不间断使用万古霉素的18岁以上脓毒症患者进行评估。我们排除了在使用万古霉素之前就患有AKI或使用后48小时内发生AKI的患者、其他病因导致的AKI患者、Ⅴ期慢性肾脏病患者以及孕妇。
我们评估了225例患者，其中135例被纳入研究。94.1%的患者进行了万古霉素血清浓度评估，其中59.3%的患者呈现中毒浓度。AKI的发生率为27.4%，平均发生在使用万古霉素的第9天。在第4至6天，万古霉素血清浓度>21.5mg/L是AKI的预测指标，曲线下面积为0.803（95%CI0.62 - 0.98，P = 0.005），比AKI诊断提前至少3天。这些患者中，20.7%死亡，第4至6天的万古霉素血清浓度被确定为与不良结局相关的危险因素。
病房患者中，万古霉素血清浓度是AKI的良好预测指标，比AKI诊断提前至少72小时。万古霉素中毒浓度与AKI相关，AKI是死亡的危险因素。此外，在Cox模型中，万古霉素血清浓度>21.5mg/L是与死亡相关的唯一变量。
