PDF(Pubmed)
Abstract：
Nowadays, lipidomics plays a crucial role in the investigation of novel biomarkers of various diseases. Its implementation into the field of clinical analysis led to the identification of specific lipids and/or significant changes in their plasma levels in patients suffering from cancer, Alzheimer\'s disease, sepsis, and many other diseases and pathological conditions. Profiling of lipids and determination of their plasma concentrations could also be helpful in the case of drug therapy management, especially in combination with therapeutic drug monitoring (TDM). Here, for the first time, a combined approach based on the TDM of colistin, a last-resort antibiotic, and lipidomic profiling is presented in a case study of a critically ill male patient suffering from Pseudomonas aeruginosa-induced pneumonia. Implementation of innovative analytical approaches for TDM (online combination of capillary electrophoresis with tandem mass spectrometry, CZE-MS/MS) and lipidomics (liquid chromatography-tandem mass spectrometry, LC-MS/MS) was demonstrated. The CZE-MS/MS strategy confirmed the chosen colistin drug dosing regimen, leading to stable colistin concentrations in plasma samples. The determined colistin concentrations in plasma samples reached the required minimal inhibitory concentration of 1 μg/mL. The complex lipidomics approach led to monitoring 545 lipids in collected patient plasma samples during and after the therapy. Some changes in specific individual lipids were in good agreement with previous lipidomics studies dealing with sepsis. The presented case study represents a good starting point for identifying particular individual lipids that could correlate with antimicrobial and inflammation therapeutic management.
摘要：
如今,脂质组学在研究各种疾病的新型生物标志物中起着至关重要的作用。其在临床分析领域的实施导致了癌症患者的特定脂质和/或血浆水平的显着变化的鉴定。老年痴呆症,脓毒症,以及许多其他疾病和病理状况。在药物治疗管理的情况下，脂质的分析和血浆浓度的测定也可能是有帮助的。特别是结合治疗药物监测（TDM）。这里,第一次,一种基于粘菌素TDM的组合方法，最后的抗生素,在一名患有铜绿假单胞菌引起的肺炎的危重男性患者的案例研究中，提出了脂质组学分析。实施TDM的创新分析方法（毛细管电泳与串联质谱的在线组合，CZE-MS/MS)和脂质组学(液相色谱-串联质谱，证明了LC-MS/MS)。CZE-MS/MS策略证实了所选择的粘菌素药物给药方案，导致血浆样品中粘菌素浓度稳定。血浆样品中测定的粘菌素浓度达到1μg/mL的所需最小抑制浓度。复杂的脂质组学方法导致在治疗期间和之后监测收集的患者血浆样品中的545脂质。特定个体脂质的一些变化与先前处理败血症的脂质组学研究非常吻合。所呈现的案例研究代表了鉴定可能与抗微生物和炎症治疗管理相关的特定个体脂质的良好起点。
