Basis for Success of Multidrug-Resistant Enterobacteriaceae

多重耐药肠杆菌科细菌的成功基础

• 批准号: 10272208
• 负责人: Frank DeLeo
• 金额: $ 125.07万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10272208
• 关键词: Aminoglycoside Antibiotics; Antibiotic Resistance; Bacteremia; Communities; Development; Enterobacteriaceae; Escherichia coli; Evolution; Goals; Hospitals; Immunotherapy; Incidence; Individual; Infection; Innate Immune System; Klebsiella Infections; Klebsiella pneumoniae; Lactamase; Link; Molecular; Monobactams; Multi-Drug Resistance; Organism; Plasmids; Prevention approach; Resistance; United States; carbapenem resistance; carbapenem-resistant Enterobacteriaceae; carbapenemase; fluoroquinolone resistance; mortality; novel therapeutic intervention; pathogen; resistant strain; success; virtual

The high incidence of Klebsiella infections in hospitals is compounded by the emergence of carbapenem-resistant organisms worldwide. Klebsiella pneumoniae is the most abundant carbapenem-resistant Enterobacteriaceae in the United States. Carbapenem-resistance is conferred largely by K. pneumoniae carbapenemase (KPC) or New Delhi metallo--lactamase 1 (NDM-1), either of which confers resistance to virtually all beta-lactam antibiotics. The most abundant strains in the United States produce KPC and are also resistant to fluoroquinolone and aminoglycoside antibiotics. These multidrug resistant strains are difficult to treat and there is a relatively high mortality rate associated with bacteremia. Although the vast majority of K. pneumoniae infections occur in hospitalized individuals, KPC is plasmid-encoded and has the potential to be readily exchanged among pathogens that cause community-associated infections, such as Escherichia coli. A K. pneumoniae lineage known as multi-locus sequence type 258 (ST258) is the most abundant lineage in the United States. Outside of carbapenem resistance, the molecular underpinnings of the emergence and success of this KPC lineage are incompletely determined, although considerable progress has been made.

医院中克雷伯氏菌感染的高发病率与世界各地出现的碳青霉烯耐药细菌的出现更加复杂。肺炎克雷伯菌是美国最丰富的碳青霉烯类耐药肠杆菌科细菌。碳青霉烯类耐药主要由肺炎克雷伯菌碳青霉烯酶(KPC)或新德里金属内酰胺酶1(NDM-1)引起，这两种酶对几乎所有的β-内酰胺类抗生素都具有耐药性。美国最丰富的菌株能产生KPC，而且对氟喹诺酮类和氨基糖苷类抗生素也有耐药性。这些耐多药菌株很难治疗，而且与菌血症相关的死亡率相对较高。虽然绝大多数肺炎克雷伯菌感染发生在住院患者中，但KPC是以质粒编码的，并有可能在引起社区相关感染的病原体之间很容易交换，如大肠杆菌。肺炎克雷伯菌谱系称为多位点序列类型258(ST258)，是美国最丰富的谱系。除了对碳青霉烯类抗生素的耐药性外，这种KPC谱系出现和成功的分子基础尚不完全确定，尽管已经取得了相当大的进展。