Department of Biology, Indiana University, Bloomington, Indiana, USA
Antimicrobial Development Specialists, LLC, Nyack, New York, USA.
Clin Microbiol Rev. 2020 Feb 26;33(2). doi: 10.1128/CMR.00047-19. Print 2020 Mar 18.
β-Lactam antibiotics have been widely used as therapeutic agents for the past 70 years, resulting in emergence of an abundance of β-lactam-inactivating β-lactamases. Although penicillinases in challenged the initial uses of penicillin, β-lactamases are most important in Gram-negative bacteria, particularly in enteric and nonfermentative pathogens, where collectively they confer resistance to all β-lactam-containing antibiotics. Critical β-lactamases are those enzymes whose genes are encoded on mobile elements that are transferable among species. Major β-lactamase families include plasmid-mediated extended-spectrum β-lactamases (ESBLs), AmpC cephalosporinases, and carbapenemases now appearing globally, with geographic preferences for specific variants. CTX-M enzymes include the most common ESBLs that are prevalent in all areas of the world. In contrast, KPC serine carbapenemases are present more frequently in the Americas, the Mediterranean countries, and China, whereas NDM metallo-β-lactamases are more prevalent in the Indian subcontinent and Eastern Europe. As selective pressure from β-lactam use continues, multiple β-lactamases per organism are increasingly common, including pathogens carrying three different carbapenemase genes. These organisms may be spread throughout health care facilities as well as in the community, warranting close attention to increased infection control measures and stewardship of the β-lactam-containing drugs in an effort to control selection of even more deleterious pathogens.
β-内酰胺类抗生素在过去的 70 年中被广泛用作治疗药物,导致大量的β-内酰胺失活β-内酰胺酶的出现。虽然青霉素酶在最初挑战了青霉素的使用,但β-内酰胺酶在革兰氏阴性菌中更为重要,特别是在肠杆菌科和非发酵菌病原体中,它们共同赋予了对所有含β-内酰胺抗生素的耐药性。关键的β-内酰胺酶是那些其基因编码在可移动元件上的酶,这些元件可在物种之间转移。主要的β-内酰胺酶家族包括质粒介导的超广谱β-内酰胺酶(ESBLs)、AmpC 头孢菌素酶和目前在全球出现的碳青霉烯酶,具有特定变体的地理偏好。CTX-M 酶包括最常见的 ESBLs,在世界各个地区都很普遍。相比之下,KPC 丝氨酸碳青霉烯酶在美洲、地中海国家和中国更为常见,而 NDM 金属β-内酰胺酶在印度次大陆和东欧更为普遍。随着β-内酰胺使用的选择性压力继续存在,每个生物体中出现的多种β-内酰胺酶越来越常见,包括携带三种不同碳青霉烯酶基因的病原体。这些生物体可能在医疗机构和社区中传播,因此需要密切关注加强感染控制措施和β-内酰胺类药物的管理,以努力控制更具危害性病原体的选择。