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目的 利用利奈唑胺治疗药物监测(TDM)数据及微生物学检测数据分析利奈唑胺在重症急性胰腺炎(SAP)伴胆道感染患者血浆和胆汁中的药动学/药效学(PK/PD)，为临床合理应用利奈唑胺提供理论支持。方法 回顾性分析2018年1月至2023年6月在医院EICU住院并使用利奈唑胺治疗且实施TDM的SAP伴胆道感染患者的基本信息，以及入院时的检查指标，利奈唑胺给药方案(给药剂量、给药途径及给药频次)，利奈唑胺TDM结果(血浆和胆汁中利奈唑胺浓度-时间数据)，临床结局和微生物学检测结果等。按照给药途径，将入选患者分成胃管内给药组和静脉注射组，各5例。采用SAS 2.0软件计算PK参数并进行组间比较。同时检测患者的微生物学培养标本，计算其最低抑菌浓度(MIC)。根据利奈唑胺在血浆和胆汁中的PK参数(AUC0-24)及其对金黄色葡萄球菌、粪肠球菌和屎肠球菌的平均MIC计算PK/PD参数AUC0-24/MIC。结果 利奈唑胺在胆汁中的药物浓度远高于血浆，静脉注射组和胃管内给药组患者的利奈唑胺在胆汁中的分布量(AUC0-24)分别为血浆的194.6%和274.3%。利奈唑胺对金黄色葡萄球菌、粪肠球菌和屎肠球菌的MIC分别为0.79、1.21和1.09μg·mL-1。静脉给药组利奈唑胺在血浆中针对金黄色葡萄球菌、粪肠球菌和屎肠球菌的PK/PD参数AUC0-24/MIC分别为135.4、88.4和98.2，胆汁中分别为263.5、172.1和191.0；胃管内给药组血浆中分别为56.2、36.7和40.7，胆汁中分别为154.2、100.7和111.7。胆道感染患者30 d的微生物学清除率为100%,30 d生存率为100%。结论 利奈唑胺治疗SAP合并胆道感染具有良好抗菌效果，对金黄色葡萄球菌、粪肠球菌、屎肠球菌均有较好疗效；对于胃管内给药的患者，在治疗期间应借助TDM的手段以优化利奈唑胺的治疗，减少细菌耐药及保障用药安全。
Abstract：AIM To analyze the pharmacokinetic/pharmacodynamics(PK/PD) of linezolid in plasma and bileusing therapeutic drug monitoring(TDM) data from patients with severe acute pancreatitis(SAP) associated with biliarytract infection, to provide theoretical support for the rational clinical application of linezolid. METHODS A retrospectiveanalysis was conducted on patients with SAP complicated by biliary tract infection who were admitted to the EICU andreceived linezolid therapy with TDM from January 2018 to June 2023. The study collected demographic characteristics,laboratory parameters upon admission, linezolid dosing regimens(dosage, administration routes, and frequency), TDMresults(concentration-time profiles in plasma and bile), clinical outcomes, microbiological test reports, etc. According to theadministration route, the selected patients were divided into the gastric tube administration group and intravenous injectiongroup, with 5 patients in each group. Pharmacokinetics(PK) parameters were calculated using SAS 2.0 software withintergroup comparisons performed. The microbiological culture specimens were also examined to calculate the minimuminhibitory concentration(MIC). PK/PD parameters(AUC0-24/MIC) were calculated based on the PK parameters AUC0-24 forlinezolid in plasma and bile and its mean MIC for Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium.RESULTS The concentration of linezolid in bile was much higher than plasma, and the distribution of linezolid in bile(AUC0-24) in intravenous and gastric patients was 194.6% and 274.3% of plasma, respectively. The MIC of linezolid forStaphylococcus aureus, Enterococcus faecalis and Enterococcus faecium were 0.79, 1.21 and 1.09 μg·mL-1, respectively. Inthe intravenous group, the AUC0-24/MIC ratios of linezolid in plasma against Staphylococcus aureus, Enterococcus faecalis,and Enterococcus faecium were 135.4, 88.4, and 98.2, respectively; corresponding values in bile were 263.5, 172.1, and191.0. In the intragastric tube group, plasma AUC0-24/MIC ratios were 56.2, 36.7, and 40.7 for the 3 pathogens, while bileconcentrations reached 154.2, 100.7, and 111.7, respectively. For patients with biliary tract infections, both groups achievedcomplete microbiological eradication and 100% survival within 30 days. CONCLUSION Linezolid represents a clinicallyappropriate antibiotic choice for SAP patients with biliary infections, demonstrating potent activity against Staphylococcusaureus, Enterococcus faecalis, and Enterococcus faecium. For patients requiring intragastric tube administration, TDMshould be implemented to optimize dosing regimens, mitigate the development of antimicrobial resistance, and ensuretreatment safety.
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基本信息:
DOI：10.19577/j.1007-4406.2025.04.006
中图分类号:R969
引用信息:
[1]石颖,高永跃,陈冰,等.利奈唑胺在重症急性胰腺炎伴胆道感染患者血浆和胆汁中的PK/PD研究[J].中国临床药学杂志,2025,34(04):272-277.DOI:10.19577/j.1007-4406.2025.04.006.
基金信息:
中华国际医学交流基金会资助项目（编号RC20200120）
2025-04-25
2025-04-25