基于真实世界数据的儿童万古霉素药物警戒研究

Research on Pharmacovigilance of Vancomycin in Children Based on Real World Data

关键词:  万古霉素  儿童  药物警戒  中国医院药物警戒系统  真实世界数据

Key words:  vancomycin  children  pharmacovigilance  chinese hospital pharmacovigilance system  real-world data

摘要:

目的 基于真实世界数据,发掘各年龄段儿童万古霉素药物的药物不良反应(ADR),并探索其影响因素。方法 采用回顾性队列研究方法,选取本院2010 年01 月至2025 年05 月使用万古霉素的儿童住院患者(1334 例次)。参考FAERS数据库、福建省及厦门市全域不ADR监测情况,采用中国医院药物警戒系统(CHPS)筛选其中发生ADR/严重ADR的例次,比较新生儿、婴幼儿和儿童人群已知的和新的严重ADR/ADR发生情况,并采用Logistic回归模型分析各队列发生率前5 位ADR的影响因素。结果 发生率较高的为血液及淋巴系统疾病,严重ADR发生率最高的为血红蛋白降低(123例次,9.22 %),且新生儿发生率显著高于婴幼儿和儿童。新的ADR包括血压下降、弥散性血管内凝血、淋巴细胞升高、淋巴结肿大、高钾血症、低白蛋白血症、心动过速等。针对发生率前5位的ADR (嗜酸性粒细胞增多、红细胞减少、血红蛋白降低、γ-谷氨酰转肽酶升高和心动过速)的进行影响因素分析,结果显示：超说明书给药增加嗜酸性粒细胞增多的风险 (OR=1.803,95 % CI：1.128-2.896),合并用药数每增加1个,发生嗜酸性粒细胞增多、红细胞减少、γ-谷氨酰转肽酶升高和心动过速的风险分别增加1.7 %、2.5 %、2.4 %和4.4 %。结论 在儿童人群特别是新生儿中使用万古霉素应注意血常规、肝功能和心电监测。建议进行分层风险管理,借助临床药师结合血药浓度监测进行早期预警并优化合并用药情况,提升万古霉素的用药安全。

Abstract:

To explore the adverse drug reactions (ADRs) of vancomycin in children of different age groups and investigate their influencing factors based on real-world data. METHODS A retrospective cohort study was conducted, selecting 1334 hospitalized pediatric patients who received vancomycin in our hospital from January 2010 to May 2025. Referring to the FAERS database, ADR monitoring data from Fujian Province and Xiamen City, the China Hospital Pharmacovigilance System (CHPS) was used to screen for cases of ADRs and severe ADRs. We compared the incidence rates of known and new severe ADRs./ADRs in newborns, infants, and children. The Logistic regression models were used to analyze the influencing factors of the top 5 ADRs in terms of incidence rate. RESULTS The highest incidence of severe ADR was hemoglobin reduction (123 cases, 9.22%), and the incidence in newborns was significantly higher than that in infants and children. The analysis of the impact on the top 5 ADRs with high incidence rates (eosinophilia, red blood cell reduction, hemoglobin reduction, elevated gamma glutamyl transpeptidase, and tachycardia) showed that off-label drug use increased the risk of eosinophilia (OR=1.803, 95% CI: 1.128-2.896), and for every increase in the number of concomitant medications, the risk of eosinophilia, red blood cell reduction, elevated gamma glutamyl transpeptidase, and tachycardia increased by 1.7%, 2.5%, 2.4%, and 4.4%, respectively. The new ADR include decreased blood pressure, disseminated intravascular coagulation, elevated lymphocytes, enlarged lymph nodes, hyperkalemia, hypoalbuminemia, tachycardia, cardiac dysfunction, acute hemorrhagic enteritis, and prolonged prothrombin time. CONCLUSION Physician should pay attention to blood routine, liver function, and electrocardiogram monitoring when using vancomycin in children, especially in newborns. Suggest implementing hierarchical risk management, utilizing clinical pharmacists combined with blood drug concentration monitoring for early warning and optimizing concomitant medication to enhance the safety of vancomycin use.