Hölsken Oliver, Sponheuer Keno, Weber Franz, Martens-Lobenhoffer Jens, Bode-Böger Stefanie M, Kloft Charlotte, Treskatsch Sascha, Angermair Stefan
Department of Anesthesiology and Intensive Care Medicine, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin, Germany.
Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Academy, Junior Clinician Scientist Program, Charitéplatz 1, 10117 Berlin, Germany.
J Pers Med. 2024 Nov 30;14(12):1135. doi: 10.3390/jpm14121135.
: A novel fixed combination of aztreonam (ATM) and avibactam (AVI) offers promising potential to treat infections with carbapenem-resistant (CRE) producing metallo-β-lactamases (MBL). This study aimed to assess the accuracy of population pharmacokinetic (PK) models for ATM-AVI in predicting in vivo concentrations in a critically ill patient with CRE infection during its first clinical use. : A 70-year-old male with septic shock due to hospital-acquired pneumonia (HAP) caused by MBL-producing was treated with ATM-AVI. Trough and peak serum concentrations (32 samples over 7 days) were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Population PK models were used to simulate complete concentration-time profiles. Bland-Altman analysis assessed model performance by comparing predicted and measured concentrations. : Median ATM trough concentrations (18.4 mg/L) remained above the minimum inhibitory concentration (MIC) of 1 mg/L for the pathogen. The Bland-Altman analysis demonstrated reasonable agreement between predicted and observed concentrations, with a relative bias (rBias) of -50.5% for ATM and -14.4% for AVI. ATM-AVI ratios remained stable. Clinical improvement and sterile blood cultures within 12 days led to intensive care unit (ICU) discharge. : Population PK models for ATM-AVI accurately predicted in vivo concentrations in a severely ill patient with HAP. Therapeutic drug monitoring (TDM) with PK modeling ensured optimal antimicrobial exposure and contributed to clinical recovery.
一种新型的氨曲南（ATM）和阿维巴坦（AVI）固定组合在治疗由产金属β-内酰胺酶（MBL）的耐碳青霉烯类肠杆菌科细菌（CRE）引起的感染方面具有广阔的应用前景。本研究旨在评估ATM-AVI群体药代动力学（PK）模型在预测CRE感染重症患者首次临床使用期间体内浓度的准确性。：一名70岁男性因产MBL的医院获得性肺炎（HAP）导致感染性休克，接受了ATM-AVI治疗。使用液相色谱-串联质谱法（LC-MS/MS）测定了谷浓度和峰浓度（7天内共32个样本）。群体PK模型用于模拟完整的浓度-时间曲线。Bland-Altman分析通过比较预测浓度和实测浓度来评估模型性能。：ATM的谷浓度中位数（18.4mg/L）保持高于病原体最低抑菌浓度（MIC）的1mg/L。Bland-Altman分析表明预测浓度和实测浓度之间具有合理的一致性，ATM的相对偏差（rBias）为-50.5%，AVI为-14.4%。ATM-AVI比值保持稳定。12天内临床症状改善且血培养无菌，患者从重症监护病房（ICU）出院。：ATM-AVI的群体PK模型准确预测了HAP重症患者的体内浓度。基于PK模型的治疗药物监测（TDM）确保了最佳的抗菌药物暴露，并有助于临床康复。
