Management of metallo-β-lactamase-producing Enterobacterales infections: a modified Delphi study

Background: and objectives Metallo-β-lactamase (MBL)-producing Enterobacterales infections are an urgent global healthcare problem with limited treatment options. To obtain greater understanding of international perspectives on optimal management of serious infections due to MBL-producing Enterobacterales, we used a modified Delphi process to elicit experts’ opinion and establish consensus. Methods: A Delphi panel comprising 10 expert physicians experienced in antimicrobial-resistant bacterial infection management were surveyed on epidemiology, disease, testing and management of MBL-producing Enterobacterales infections. Consensus statements were based on survey responses and reviewed by the panel for endorsement or revisions to achieve consensus during a virtual meeting. Results: All panellists acknowledged MBL-producing Enterobacterales as a key source of antimicrobial resistance and infection in most countries. All agreed these infections have high morbidity and mortality, leading to the need for critical-level care, longer hospital stays and significant healthcare costs. The negative clinical and economic consequences of MBL-producing Enterobacterales are compounded by inappropriate use of multidrug antimicrobial regimens. Therefore, a specific MBL-targeting agent is considered desirable. When aztreonam-avibactam and cefiderocol are available, the preferred first-line treatment is aztreonam-avibactam, per in vitro data showing aztreonam-avibactam activity against >90% of New Delhi MBL-producing Enterobacterales. If aztreonam-avibactam or cefiderocol are unavailable, treatment options are limited to co-administration of antimicrobials. Regional differences made it difficult to achieve unanimous consensus across all survey questions due to differences in patient factors, local epidemiology and testing availability. Conclusions: The Delphi panel reached consensus on optimal management of MBL-producing Enterobacterales, confirming need for targeted MBL treatment, with monotherapy preferred where available.