Beyond the Spotlight: Enterobacter spp. as Overlooked Carbapenemase Producers in Europe

Antimicrobial resistance (AMR) poses a critical global health challenge, with carbapenemase-producing Enterobacterales (CPE) representing one of the most urgent threats. While Klebsiella pneumoniae and Escherichia coli have been the focus of most surveillance programs, Enterobacter spp., members of the Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli (ESKAPEE) group, remain an underrecognized but increasingly important reservoir of carbapenemase genes in Europe. Despite being categorized by the World Health Organization (WHO) as "critical-priority" pathogens, Enterobacter spp. are largely excluded from major AMR surveillance frameworks, creating blind spots in detection and control. This review summarizes the taxonomy, intrinsic resistance mechanisms, and clinical relevance of Enterobacter spp., with a particular focus on carbapenemase epidemiology across Europe. We highlight the distribution and genetic context of major carbapenemases, including VIM, OXA-48-like, KPC, and NDM, and discuss emerging or minor enzymes such as IMI, FRI, GES, and IMP. Epidemiological data reveal shifting dominance patterns over time, with VIM enzymes consolidating their prevalence after 2015, while OXA-48-like and KPC declined, and NDM gained ground. The genetic diversity of Enterobacter spp., coupled with their ability to act as both nosocomial pathogens and silent intestinal or environmental reservoirs, facilitates the dissemination of carbapenemase genes via epidemic plasmids and clonal expansion. Addressing the growing impact of carbapenemase-producing Enterobacter spp. requires their systematic inclusion in national and international monitoring programs, expanded use of genomic epidemiology in clinical microbiology, and better alignment between research, clinical practice, and policy. A One Health approach is essential to curb the spread of carbapenemases across human, environmental, and animal reservoirs, and to safeguard the remaining therapeutic options.