Abstract：
β-Lactamases are bacterial enzymes that inactivate β-lactam antibiotics and, as such, are the most prevalent cause of antibiotic resistance in Gram-negative bacteria. The ever-increasing production and worldwide dissemination of bacterial strains producing carbapenemases is currently a global health concern. These enzymes catalyze the hydrolysis of carbapenems - the β-lactam antibiotics with the broadest spectrum of activity that are often considered as drugs of last resort. The incidence of carbapenem-resistant pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and carbapenemase or extended spectrum beta-lactamase (ESBL)-producing Enterobacterales, which are frequent in clinical settings, is worrisome since, in some cases, no therapies are available. These include all metallo-β-lactamases (VIM, IMP, NDM, SMP, and L1), and serine-carbapenemases of classes A (KPC, SME, IMI, and GES), and of classes D (OXA-23, OXA-24/40, OXA-48 and OXA-58). Consequently, the early diagnosis of bacterial strains harboring carbapenemases is a pivotal task in clinical microbiology in order to track antibiotic bacterial resistance and to improve the worldwide management of infectious diseases. Recent research efforts on the development of chromogenic and fluorescent chemical sensors for the specific and sensitive detection and quantification of β-lactamase production in multidrug-resistant pathogens are summarized herein. Studies to circumvent the main limitations of the phenotypic and molecular methods are discussed. Recently reported chromogenic and fluorogenic cephalosporin- and carbapenem-based β-lactamase substrates will be reviewed as alternative options to the currently available nitrocefin and related compounds, a chromogenic cephalosporin-based reagent widely used in clinical microbiology laboratories. The scope of these new chemical sensors, along with the synthetic approaches to synthesize them, is also summarized.
摘要：
β-内酰胺酶是使β-内酰胺抗生素失活的细菌酶，因此，是革兰氏阴性细菌中抗生素耐药性的最普遍原因。产生碳青霉烯酶的细菌菌株的不断增加的产量和全球传播目前是全球健康关注的问题。这些酶催化碳青霉烯类的水解，碳青霉烯类是具有最广泛活性的β-内酰胺抗生素，通常被认为是万不得已的药物。耐碳青霉烯类病原菌如铜绿假单胞菌,鲍曼不动杆菌和碳青霉烯酶或产超广谱β-内酰胺酶（ESBL）的肠杆菌，这在临床环境中很常见，令人担忧，因为，在某些情况下,没有可用的治疗方法。这些包括所有金属-β-内酰胺酶(VIM，IMP,NDM,SMP,和L1），和A类丝氨酸-碳青霉烯酶(KPC，中小企业，IMI,和GES），以及D类(OXA-23、OXA-24/40、OXA-48和OXA-58)。因此,早期诊断携带碳青霉烯酶的细菌菌株是临床微生物学的一项关键任务，以追踪抗生素细菌的耐药性并改善全球感染性疾病的管理。本文总结了有关开发显色和荧光化学传感器的最新研究工作，这些传感器用于特异性和灵敏地检测和定量多药耐药病原体中的β-内酰胺酶的产生。讨论了规避表型和分子方法主要局限性的研究。最近报道的显色和荧光头孢菌素和碳青霉烯类的β-内酰胺酶底物将作为目前可用的硝基红霉素和相关化合物的替代选择进行审查，一种基于头孢菌素的显色试剂，广泛用于临床微生物学实验室。这些新型化学传感器的范围，以及合成它们的合成方法，也进行了总结。
