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美罗培南暴露与降解水平对化脓性脑膜炎疗效的影响
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| 篇名： | 美罗培南暴露与降解水平对化脓性脑膜炎疗效的影响 |
| TITLE： | Effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis |
| 摘要： | 目的 探讨美罗培南暴露与降解水平对化脓性脑膜炎（PM）疗效的影响。方法前瞻性纳入南京医科大学附属苏州医院2022年1月至2025年6月收治的131例接受美罗培南治疗的PM患者，收集其相关资料，并根据疗效分为治愈组（91例）和未治愈组（40例）。采用高效液相色谱-串联质谱法测定美罗培南谷浓度及开环代谢物浓度。通过单因素分析、多因素Logistic回归分析、受试者工作特征（ROC）曲线及相关性分析筛选影响疗效的危险因素、评估其预测效能及相关性。结果单因素分析显示，血清肌酐、肌酐清除率、美罗培南最低抑菌浓度≥16μg/mL、脑脊液红细胞计数、脑脊液白细胞计数、脑脊液葡萄糖含量、血药谷浓度、血中开环代谢物浓度/谷浓度比值及鞘内注射与否均与疗效相关（P＜0.05）。多因素Logistic回归分析结果显示，血清肌酐、血中开环代谢物浓度/谷浓度比值、鞘内注射及脑脊液葡萄糖含量为抗感染疗效不达标的影响因素（P＜0.05）。ROC曲线分析显示，当血中开环代谢物浓度/谷浓度比值＞2.854（AUC＝0.647）、血清肌酐＜59.5μmol/L（AUC＝0.647）及脑脊液葡萄糖含量＜3.37mmol/L（AUC＝0.709）时，治疗失败风险显著增加（P＜0.05）。相关性分析显示，美罗培南血药谷浓度与其开环代谢物浓度呈正相关（R2＝0.1345，P＜0.0001）。结论美罗培南药物暴露水平不足与降解过快是影响PM抗感染疗效的关键机制，血中开环代谢物浓度/谷浓度比值升高、血清肌酐水平低、未行鞘内注射及脑脊液葡萄糖含量低均为疗效不佳的独立危险因素。 |
| ABSTRACT： | OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy. |
| 期刊： | 2025年第36卷第24期 |
| 作者： | 李彤彤；孙坚彤；陈相龙；邓朋；薛彦平；肖遥；杨利娟；徐金慧；虞燕霞；唐莲 |
| AUTHORS： | LI Tongtong，SUN Jiantong， CHEN Xianglong，DENG Peng，XUE Yanping，XIAO Yao，YANG Lijuan，XU Jinhui，YU Yanxia，TANG Lian |
| 关键字： | 美罗培南；化脓性脑膜炎；谷浓度；开环代谢物；疗效；危险因素 |
| KEYWORDS： | meropenem； purulent meningitis； trough concentration； open-loop metabolite； therapeutic effect； risk factor |
| 阅读数： | 3 次 |
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