Carbapenems and alternative β-lactams for the treatment of infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae: What impact on intestinal colonisation resistance?

Abstract

The ongoing pandemic of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) is responsible for a global rise in carbapenem consumption that may hasten the dissemination of carbapenemase-producing Enterobacteriaceae (CPE). Hence, carbapenem sparing through the use of alternative β-lactams is increasingly considered as a potential option in patients with ESBL-E infections. However, at the individual level, this strategy implies an in-depth understanding of how carbapenems and their alternatives impair the gut microbiota, especially the anaerobic bacteria and the colonisation resistance (CR) that it confers. In this review, we sought to appraise the impact of carbapenems and their main alternatives for ESBL-E infections (namely β-lactam/β-lactamase inhibitor combinations, cephamycins and temocillin) on the gut ecosystem and the resulting hazard for acquisition of CPE. Although limited, the available evidence challenges our perception of the ecological side effects of these antimicrobials and highlights knowledge gaps regarding antibiotic-induced alterations in intestinal CR. These alterations may depend not only on anti-anaerobic properties but also on a panel of parameters with marked interindividual variability, such as baseline characteristics of the gut microbiota or the degree of biliary excretion for the considered drug. In the current context of ESBL-E dissemination and increasing opportunities for carbapenem-sparing initiatives, large, comparative, high-quality studies based on new-generation sequencing tools are more than ever warranted to better define the positioning of alternative β-lactams in antimicrobial stewardship programmes.

Keywords: Antimicrobial stewardship; Carbapenems; Colonisation resistance; De-escalation; Non-carbapenem β-lactams.