Clinical management of infections caused by enterobacteriaceae that express extended-spectrum β-Lactamase and AmpC enzymes

Abstract

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.