Effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis

LI Tongtong; SUN Jiantong; CHEN Xianglong; DENG Peng; XUE Yanping; XIAO Yao; YANG Lijuan; XU Jinhui; YU Yanxia; TANG Lian

doi:10.6039/j.issn.1001-0408.2025.24.12

您当前的位置：

首页 >

文章列表页 >

Effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis

更新时间：2025-12-26

- Effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis
- ZHONGGUO YAOFANG Vol. 36, Issue 24, Pages: 3084-3090(2025)
- 作者机构：
  
  1.南京医科大学附属苏州医院/苏州市立医院药学部，江苏苏州　215002
  2.南京医科大学附属苏州医院/苏州市立医院神经外科，江苏苏州　215002
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.24.12
  CLC： R969;R978.1
- Received：24 July 2025，
  
  Revised：2025-08-12，
  
  Accepted：21 November 2025，
  
  Published：30 December 2025
- 稿件说明：
移动端阅览
李彤彤,孙坚彤,陈相龙,等.美罗培南暴露与降解水平对化脓性脑膜炎疗效的影响 ^Δ[J].中国药房,2025,36(24):3084-3090.

LI Tongtong,SUN Jiantong,CHEN Xianglong,et al.Effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis[J].ZHONGGUO YAOFANG,2025,36(24):3084-3090.
李彤彤,孙坚彤,陈相龙,等.美罗培南暴露与降解水平对化脓性脑膜炎疗效的影响 ^Δ[J].中国药房,2025,36(24):3084-3090. DOI： 10.6039/j.issn.1001-0408.2025.24.12.

LI Tongtong,SUN Jiantong,CHEN Xianglong,et al.Effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis[J].ZHONGGUO YAOFANG,2025,36(24):3084-3090. DOI： 10.6039/j.issn.1001-0408.2025.24.12.

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≥16 μg/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（

＜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（

＜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＜59.5 μmol/L（AUC＝0.647）及脑脊液葡萄糖含量＜3.37 mmol/L（AUC＝0.709）时，治疗失败风险显著增加（

＜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（

＝0.134 5，

＜0.000 1）。

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 （

＜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 efficacy （

＜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 （

＜0.05）. Correlation analysis showed that the

blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （

＝0.134 5，

＜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.

关键词

Keywords

references

孙虎 . 颅脑外伤术后颅内感染相关危险因素分析 [J ] . 中华医院感染学杂志， 2013 ， 23 （ 1 ）： 65 - 67 .

刘佳微，达哇卓玛，冶挺，等 . 开颅术后中枢神经系统感染的危险因素分析 [J ] . 重庆医学， 2025 ， 54 （ 5 ）： 1176 - 1179 .

中国医师协会神经外科医师分会神经重症专家委员会，北京医学会神经外科学分会神经外科危重症学组 . 神经外科中枢神经系统感染诊治中国专家共识： 2021版 [J ] . 中华神经外科杂志， 2021 ， 37 （ 1 ）： 2 - 15 .

卫艳平 . 美罗培南双途径给药在重症颅脑损伤术后颅内感染患者辅助治疗的效果评价 [J ] . 中国药物与临床， 2022 ， 22 （ 3 ）： 219 - 222 .

韦汝华，曹雯，陆雅婷，等 . 中枢性神经系统感染患者美罗培南血药浓度达标情况及影响因素分析 [J ] . 中国临床药理学与治疗学， 2024 ， 29 （ 10 ）： 1146 - 1151 .

LIEBCHEN U ， RAKETE S ， VOGESER M ， et al . The role of non-enzymatic degradation of meropenem-insights from the bottle to the body [J ] . Antibiotics（Basel）， 2021 ， 10 （ 6 ）： 715 .

GIJSEN M ， FILTJENS B ， ANNAERT P ， et al . Meropenem stability in human plasma at －20 ℃：detailed assessment of degradation [J ] . Antibiotics（Basel）， 2021 ， 10 （ 4 ）： 449 .

CARLIER M ， ROBERTS J A ， STOVE V ， et al . A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients [J ] . Antimicrob Agents Chemother ， 2015 ， 59 （ 8 ）： 4689 - 4694 .

NAU R ， SÖRGEL F ， EIFFERT H . Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections [J ] . Clin Microbiol Rev ， 2010 ， 23 （ 4 ）： 858 - 883 .

肖波，胡凯 . 化脓性脑膜脑炎的急性期诊治 [J ] . 中华神经科杂志， 2022 ， 55 （ 8 ）： 877 - 885 .

戴维·吉尔伯特，亨利·钱伯斯，迈克尔·萨格，等 . 热病：桑福德抗微生物治疗指南：新译第53版 [M ] . 范洪伟，译. 北京：中国协和医科大学出版社， 2024 ： 716 .

RAKETE S ， SCHUSTER C ， PAAL M ， et al . An isotope-dilution LC-MS/MS method for the simultaneous quantification of meropenem and its open-ring metabolite in serum [J ] . J Pharm Biomed Anal ， 2021 ， 197 ： 113944 .

石璐，陈芳，鲁广先，等 . 医院获得性肺炎患者美罗培南血药浓度不达标的危险因素分析 [J ] . 中国药房， 2022 ， 33 （ 19 ）： 2388 - 2392 .

GUILHAUMOU R ， BENABOUD S ， BENNIS Y ， et al . Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics（Société Française de Pharmacologie et Thérapeutique-SFPT） and the French Society of Anaesthesia and Intensive Care Medicine（Société Française d’Anesthésie et Réanimation-SFAR） [J ] . Crit Care ， 2019 ， 23 （ 1 ）： 104 .

SALMERÓN-GÓMEZ R ， GARCÍA-GARCÍA C B ， GARCÍA-PÉREZ J . A redefined variance inflation factor：overcoming the limitations of the variance inflation factor [J ] . Comput Econ ， 2025 ， 65 （ 1 ）： 337 - 363 .

LUO J F ， LIU J ， LIN H F ， et al . Optimization of meropenem dosing regimens in critically ill patients with augmented renal clearance [J ] . Front Med（Lausanne）， 2025 ， 12 ： 1550053 .

中国医药教育协会感染疾病专业委员会 . 抗菌药物药代动力学/药效学理论临床应用专家共识 [J ] . 中华结核和呼吸杂志， 2018 ， 41 （ 6 ）： 409 - 446 .

徐明，王强，史中华，等 . 美罗培南静脉持续泵入时血液和脑脊液药物浓度的测定 [J ] . 首都医科大学学报， 2007 ， 28 （ 5 ）： 584 - 586 .

LODISE T P ， LOMAESTRO B ， DRUSANO G L . Piperacillin-tazobactam for Pseudomonas aeruginosa infection：clinical implications of an extended-infusion do-sing strategy [J ] . Clin Infect Dis ， 2007 ， 44 （ 3 ）： 357 - 363 .

RUSU A ， OANCEA OL ， DONICI E ， et al . Recent develop-ments in penem antibiotics：structural and therapeutic perspectives [J ] . Molecules ， 2025 ， 30 （ 10 ）： 2126 .

JAMIESON C ， ALLWOOD M C ， STONKUTE D ， et al . Investigation of meropenem stability after reconstitution：the influence of buffering and challenges to meet the NHS yellow cover document compliance for continuous infusions in an outpatient setting [J ] . Eur J Hosp Pharm ， 2020 ， 27 （ e1 ）： e53 - e57 .

WEN Z P ， FAN S S ， DU C ， et al . Drug-drug interaction between valproic acid and meropenem：a retrospective analysis of electronic medical records from neurosurgery inpatients [J ] . J Clin Pharm Ther ， 2017 ， 42 （ 2 ）： 221 - 227 .

MORTENSEN J S ， JENSEN B P ， DOOGUE M . Preanaly-tical stability of flucloxacillin，piperacillin，tazobactam，meropenem，cefalexin，cefazolin，and ceftazidime in therapeutic drug monitoring：a structured review [J ] . Ther Drug Monit ， 2022 ， 44 （ 6 ）： 709 - 719 .

曹隽，沈隽，祝禾辰，等 . 低血清肌酐对危重患者的临床意义 [J ] . 中华临床医师杂志（电子版）， 2011 ， 5 （ 22 ）： 6791 - 6794 （ 2011-11-15 ）[ 2025-07-04 ] . https：//d.wanfangdata.com.cn/periodical/zhlcyszz201122063 https://d.wanfangdata.com.cn/periodical/zhlcyszz201122063 .

吴京南，刘亦伟，许建文，等 . 基于NONMEM法构建美罗培南群体药代动力学模型 [J ] . 海峡药学， 2020 ， 32 （ 8 ）： 41 - 45 .

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Analysis of risk factors for multidrug resistance in patients with ventilator-associated pneumonia complicated by prolonged invasive mechanical ventilation in the ICU

Correlation of the steady-state minimal concentration with AUC₂₄/MIC of vancomycin and analysis of risk factors for treatment failure in pediatric patients

Construction of risk prediction model for non-compliance with inhalation medication in COPD patients

Analysis of the occurrence time and risk factors of anemia in AIDS patients caused by HAART regimen containing zidovudine

Analysis of risk factors for hypokalemia caused by amphotericin B liposome

Related Author

HU Zhicheng

CHEN Yongwu

HU Tongtong

WU Xiuping

CAI Ningfang

SONG Ying

WANG Jing

XIAO Zhifeng

Related Institution

Dept. of Pharmacy， Shexian Branch of the Second Affiliated Hospital of Zhejiang University School of Medicine

Dept. of Pharmacy， the First Affiliated Hospital of USTC （Anhui Provincial Hospital）

Dept. of Critical Care Medicine， Shexian Branch of the Second Affiliated Hospital of Zhejiang University School of Medicine

Dept. of Pharmacy， Xiamen Children’s Hospital/Children’s Hospital of Fudan University at Xiamen

Dept. of Pharmacy， the First Hospital of Qinhuangdao

⁰