The influence of liver disease on the pharmacokinetic profile, the risk of acute kidney injury, and excessive drug exposure in patients treated with vancomycin was examined. A retrospective cohort study was performed with patients discharged from a medical center between January 2011 and June 2018 who received vancomycin therapy. Patients were stratified according to liver dysfunction (no to mild liver dysfunction (NMLD) and moderate to severe liver dysfunction (MSLD) based on the Child–Pugh score. The risk of acute kidney injury was compared between patients who were stratified by the attainment of a target serum trough concentration (10 mg/dL to 20 mg/dL) and the vancomycin ratio formed between the area under the curve and minimum inhibitory concentration. The impact of liver dysfunction and a daily dose of vancomycin on the risk of acute kidney injury and vancomycin AUC:MIC > 600 were tested using logistic regression with and without adjusting for the study variables. A total of 408 patients empirically treated with vancomycin were included in this study (237 with NMLD and 171 with MSLD). Mean vancomycin trough concentrations (17.5 ± 8.4 mg/dL versus 15.3 ± 5.2 mg/dL, p = 0.0049) and AUC:MIC ratios (549.4 ± 217.2 versus 497.5 ± 117.3, 0.0065) were significantly higher in the MSLD group when compared to the NMLD group, respectively. Vancomycin clearance was also lower in the MSLD group and corresponded to a longer half-life. The proportion of patients who developed acute kidney injury was greater in patients with MSLD when compared to NMLD (7.6% versus 3.8%, respectively; p = 0.0932); however, the difference was statistically insignificant. Furthermore, supratherapeutic serum trough concentrations and AUC:MIC ratios were more common in the MSLD group versus the NMLD group (27.5% versus 13.9%, p = 0.0007 and 28.7% versus 17.3%, respectively; p = 0.0063). MSLD correlates with an increased risk of supratherapeutic vancomycin exposure. Although patients with MSLD had a higher risk of acute kidney injury, the difference was not significant.

中文翻译：

---

肝功能不全患者中万古霉素毒性的风险

研究了万古霉素治疗患者肝脏疾病对药代动力学，急性肾损伤风险和过度药物暴露的影响。对2011年1月至2018年6月期间从医疗中心出院并接受万古霉素治疗的患者进行了回顾性队列研究。根据Child–Pugh评分，根据肝功能障碍（无至轻度肝功能障碍（NMLD）和中度至重度肝功能障碍（MSLD））对患者进行分层。目标血清谷浓度（10 mg / dL至20 mg / dL）以及曲线下面积与最小抑制浓度之间形成的万古霉素比。肝功能不全和日剂量万古霉素对急性肾损伤和万古霉素AUC：MIC> 600的影响使用logistic回归进行了检验，其中有和没有对研究变量进行调整。该研究共包括408例接受万古霉素治疗的患者（其中NMLD患者237例，MSLD患者171例）。与MSLD组相比，MSLD组的平均万古霉素谷浓度（17.5±8.4 mg / dL对15.3±5.2 mg / dL，p = 0.0049）和AUC：MIC比（549.4±217.2对497.5±117.3，0.0065）显着更高。 NMLD组分别。MSLD组中万古霉素清除率也较低，对应于更长的半衰期。与NMLD相比，MSLD患者发生急性肾脏损伤的比例更高（分别为7.6％和3.8％； p = 0.0932）。然而，差异在统计上不明显。此外，MSLD组和NMLD组的治疗上血清谷浓度和AUC：MIC比率更常见（分别为27.5％和13.9％，p = 0.0007和28.7％对17.3％； p = 0.0063）。MSLD与治疗上万古霉素暴露的风险增加相关。尽管MSLD患者发生急性肾损伤的风险更高，但差异并不显着。