Controversies over the management of infections caused by Amp-C- and ESBL-producing Enterobacterales: what questions remain for future studies?

Abstract

Purpose of review: The continuous rise in infections caused by third-generation cephalosporin-resistant Enterobacterales (e.g. extended-spectrum beta-lactamase- or AmpC-producing Enterobacterales ) is a major health concern. Carbapenems are regarded as the antibiotics of choice for the treatment of these infections. However, their indiscriminant use is not without consequences, and has contributed to the emergence of carbapenem-resistant Enterobacterales .In this review, we discuss the available evidence supporting the use of other betalactams, nonbetalactams and the new betalactams/beta-lactamase inhibitors (BLA/BLI) to treat these infections. We also analyze unresolved issues in this field.

Recent findings: Piperacillin tazobactam (PTZ) was classically recommended as a carbapenem-sparing agent. However, data have emerged against its use and it is now a controversial recommendation. IDSA, European and British guidelines reject the empirical use of PTZ for these pathogens, reserving its use for rare clinical situations.Other issues that continue to generate debate are the use of extended infusion (3 h) PTZ, the use of older antibiotics, a shortened course of carbapenems and reserving the new BLA/BLI for these infections.

Summary: New treatment strategies should be based on clinical evidence, local epidemiology and the microbiological activity of these drugs.