Bai Hehe, Li Huan, Nie Xiaojing, Yao Yanqin, Han Xiaonian, Wang Jinping, Peng Lirong
Department of Pharmacy, Xi' an Central Hospital, Xi'an, Shaanxi, China.
School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
PLoS One. 2023 Sep 21;18(9):e0291658. doi: 10.1371/journal.pone.0291658. eCollection 2023.
Cefoperazone/sulbactam-induced hypoprothrombinaemia is associated with longer hospital stays and increased risk of death. The aim of this study was to develop and validate a nomogram for predicting the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia in hospitalized adult patients. This retrospective cohort study involved hospitalized adult patients at Xi'an Central Hospital from January 2020 to December 2022 based on the Chinese pharmacovigilance system developed and established by the Adverse Drug Reaction Monitoring Center in China. Independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were obtained using multivariate logistic regression and were used to develop and establish the nomogram. According to the same standard, the clinical data of hospitalized patients using cefoperazone/sulbactam at the Third Affiliated Hospital of Xi'an Medical University from January 1, 2023 to June 30, 2023 were collected as the external validation group. The 893 hospitalized patients included 95 who were diagnosed with cefoperazone/sulbactam-induced hypoprothrombinaemia. Our study enrolled 610 patients: 427 in the training group and 183 in the internal validation group. The independent predictors of cefoperazone/sulbactam-induced hypoprothrombinaemia were surgery (odds ratio [OR] = 5.279, 95% confidence interval [CI] = 2.597-10.729), baseline platelet count ≤50×109/L (OR = 2.492, 95% CI = 1.110-5.593), baseline hepatic dysfunction (OR = 12.362, 95% CI = 3.277-46.635), cumulative defined daily doses (OR = 1.162, 95% CI = 1.162-1.221) and nutritional risk (OR = 16.973, 95% CI = 7.339-39.254). The areas under the curve (AUC) of the receiver operating characteristic for the training and internal validation groups were 0.909 (95% CI = 0.875-0.943) and 0.888 (95% CI = 0.832-0.944), respectively. The Hosmer-Lemeshow tests yielded p = 0.475 and p = 0.742 for the training and internal validation groups, respectively, confirming the goodness of fit of the nomogram model. In the external validation group (n = 221), the nomogram was equally robust in cefoperazone/sulbactam-induced hypoprothrombinaemia (AUC = 0.837, 95%CI = 0.736-0.938). The nomogram model constructed in this study had good predictive performance and extrapolation, which can help clinicians to identify patients at high risk of cefoperazone/sulbactam-induced hypoprothrombinaemia early. This will be useful in preventing the occurrence of cefoperazone/sulbactam-induced hypoprothrombinaemia and allowing timely intervention measures to be performed.
头孢哌酮/舒巴坦引起的低凝血酶原血症与住院时间延长和死亡风险增加相关。本研究的目的是开发并验证一种列线图，用于预测住院成年患者发生头孢哌酮/舒巴坦引起的低凝血酶原血症的风险。这项回顾性队列研究纳入了2020年1月至2022年12月在西安中心医院住院的成年患者，数据来源于中国药品不良反应监测中心建立的中国药物警戒系统。使用多因素逻辑回归分析得出头孢哌酮/舒巴坦引起的低凝血酶原血症的独立预测因素，并用于开发和建立列线图。按照相同标准，收集了2023年1月1日至2023年6月30日在西安医学院第三附属医院使用头孢哌酮/舒巴坦的住院患者的临床数据作为外部验证组。893例住院患者中，95例被诊断为头孢哌酮/舒巴坦引起的低凝血酶原血症。本研究共纳入610例患者，其中训练组427例，内部验证组183例。头孢哌酮/舒巴坦引起的低凝血酶原血症的独立预测因素包括手术（比值比[OR]=5.279，95%置信区间[CI]=2.597-10.729）、基线血小板计数≤50×10⁹/L（OR=2.492，95%CI=1.110-5.593）、基线肝功能不全（OR=12.362，95%CI=3.277-46.635）、累计限定日剂量（OR=1.162，95%CI=1.162-1.221）和营养风险（OR=16.973，95%CI=7.339-39.254）。训练组和内部验证组的受试者工作特征曲线下面积（AUC）分别为0.909（95%CI=0.875-0.943）和 0.888（95%CI=0.832-0.944）。Hosmer-Lemeshow检验显示，训练组和内部验证组的p值分别为0.475和0.742，证实了列线图模型的拟合优度。在外部验证组（n=221）中，该列线图对头孢哌酮/舒巴坦引起的低凝血酶原血症同样具有良好的预测能力（AUC=0.837，95%CI=0.736-0.938）。本研究构建的列线图模型具有良好的预测性能和外推性，有助于临床医生早期识别发生头孢哌酮/舒巴坦引起的低凝血酶原血症的高危患者。这对于预防头孢哌酮/舒巴坦引起低凝血酶原血症的发生以及及时采取干预措施具有重要意义。
