Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae: Update on Molecular Epidemiology and Treatment Options

Abstract

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are a major global public health concern. Presently, Escherichia coli with CTX-Ms are the most common species associated with global ESBLs; CTX-M-15 is the most frequent CTX-M worldwide and is followed by CTX-M-14, which is often found in South-East Asia. Recent surveillance studies showed that CTX-M-27 is emerging in certain parts of the world especially in Japan and Europe. The population structure of ESBL-producing E. coli is dominated globally by an high-risk clone named ST131. Escherichia coli ST131 belongs to three clades (A, B, and C) and three different subclades (C1, C1-M27, and C2). Clade C1-M27 is associated with bla_CTX-M-27, and C2 with bla_CTX-M-15. Recent whole genome sequencing studies have shown that clade C has evolved from clade B in a stepwise fashion, resulting in one of the most influential global antimicrobial resistance clones that has emerged during the 2000's. Other important E. coli clones that have been detected among ESBL producers include ST405, ST38, ST648, ST410, and ST1193. The INCREMENT project has shown that ertapenem is as effective as other carbapenems for treating serious infections due to ESBL-producing Enterobacteriaceae. The results of the MERINO open-label randomized controlled study has provided clear evidence that piperacillin-tazobactam should be avoided for targeted therapy of blood-stream infections due to ESBL-producing E. coli and K. pneumoniae, regardless of the patient population, source of infection, bacterial species, and susceptibility result of piperacillin-tazobactam. Research is still warranted to define the optimal therapy of less severe infections due to ESBL-producing Enterobactericeae.