基于mVOCs指纹图EESI-MS快速检测耐碳青霉烯类革兰阴性杆菌菌血症的研究

耐碳青霉烯类革兰阴性杆菌（CRO）菌血症患者病死率高，早期优化治疗是成功降低死亡率的关键。我们前期应用电喷雾萃取电离质谱（EESI-MS）检测患者血培养瓶中细菌挥发性代谢产物（mVOCs）时，发现有某些特定的信号分子（m/z 59，m/z 91），经证实这些分子为碳青霉烯酶水解亚胺培南产生的mVOCs。据此我们推测细菌水解碳青霉烯类药物能释放特定的mVOCs或形成特定的mVOCs指纹图，而特定的mVOCs指纹图可用于CRO菌血症的检测。本项目拟采用EESI-MS检测细菌水解碳青霉烯类药物产生的mVOCs，采用主成分分析各类型碳青霉烯酶特有的mVOCs标志物或mVOCs指纹图，采用多级串联质谱明确标志物的分子结构，建立mVOCs指纹图库检测CRO菌血症。旨在研发一种基于细菌水解碳青霉烯类药物产生的mVOCs指纹图，快速检测CRO菌血症的新方法，为早期合理用药和控制CRO菌血症提供依据

Bacteremia caused by carbapenem-resistant gram-negative bacilli (CRO) have a high morbidity and early optimization of treatment is the key to successful reduction of mortality. In our previous application of electrospray extraction ionization mass spectrometry (EESI-MS) to detect volatile organic compounds (mVOCs) in blood culture bottles, we found that certain blood molecules have specific signal molecules (m / z 59, m / z 91). Subsequent investigation have confirmed that these molecules are mVOCs produced by carbapenemase hydrolysis of imipenem. Based on this finding, we speculate that bacterial hydrolysis of carbapenems in blood cultures can release unique mVOCs or form unique mVOCs fingerprints, and characteristic mVOCs fingerprints can be used for CRO detection. This project intends to use EESI-MS to detect mVOCs produced by bacterial hydrolysis of carbapenems in blood culture bottles, and use principal components to analyze mVOCs markers or mVOCs fingerprints released by carbapenems hydrolyzed by various types of carbapenemases.Multi-stage tandem mass spectrometry was used to determine the molecular structure of the marker, and a fingerprint library of mVOCs was established to detect CRO bacteremia. The aim is to develop a new method based on fingerprints of mVOCs produced by bacterial hydrolysis of carbapenems to quickly detect CR0 bacteremia, and provide a basis for early rational drug use and control of CRO bacteremia.