Harris Patrick N A
Infection and Immunity Theme, University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia.
Semin Respir Crit Care Med. 2015 Feb;36(1):56-73. doi: 10.1055/s-0034-1398387. Epub 2015 Feb 2.
The production of β-lactamase is the principal mechanism by which gram-negative bacteria resist the action of β-lactam antibiotics. In recent decades, there has been an alarming explosion in the diversity, global dissemination, host range, and spectrum of activity of β-lactamases. This has been most clearly reflected by the marked increase in infections caused by bacteria that express extended-spectrum β-lactamases (ESBLs). Some bacterial species possess chromosomally encoded broad-spectrum cephalosporinases (AmpC) that may be expressed at high level by mutational loss of regulatory genes and are intrinsic in some common Enterobacteriaceae, such as Enterobacter spp. Recently, high-level AmpC production has also been seen in new species such as Escherichia coli via plasmid acquisition. ESBL and AmpC producers present challenges to susceptibility testing and the selection of appropriate antimicrobial therapy. This review describes the current global epidemiology of ESBL producers, examines reported risk factors for infections caused by gram-negative bacteria that express ESBL or AmpC enzymes, and discusses the options for antimicrobial therapy, including "re-discovered" older antibiotics and novel agents in development.
β-内酰胺酶的产生是革兰氏阴性菌抵抗β-内酰胺类抗生素作用的主要机制。近几十年来，β-内酰胺酶的多样性、全球传播、宿主范围及活性谱出现了惊人的激增。这在产超广谱β-内酰胺酶（ESBLs）细菌引起的感染显著增加中得到了最明显的体现。一些细菌物种拥有染色体编码的广谱头孢菌素酶（AmpC），这些酶可能因调控基因的突变性缺失而高水平表达，并且在一些常见的肠杆菌科细菌（如肠杆菌属）中是固有存在的。最近，通过质粒获得，在新的菌种如大肠杆菌中也发现了高水平的AmpC产生。产ESBL和AmpC的细菌给药敏试验及选择合适的抗菌治疗带来了挑战。本综述描述了产ESBL细菌目前的全球流行病学情况，研究了报道的由产ESBL或AmpC酶的革兰氏阴性菌引起感染的危险因素，并讨论了抗菌治疗的选择，包括“重新发现”的较老抗生素以及正在研发的新型药物。
