Clinical and microbiological analyses of colistin-resistant strains among carbapenem-resistant <i>Enterobacter cloacae</i> complex clinical isolates

Carbapenem-resistant <i>Enterobacter cloacae</i> complex (CR-ECC), which is rapidly increasing as the cause of nosocomial infections, has limited treatment options. The aim of this study is to investigate the microbiological and clinical traits and molecular epidemiology of isolates of CR-ECC and provide guidance for antibiotic selection in clinical practice. Clinical CR-ECC isolates (ertapenem MIC ≥ 2 mg/L) were collected from 2021 to 2022. Species identification was performed using <i>hsp60</i> gene analysis, and antibiotic susceptibility tests were conducted by broth microdilution. The clinical characteristics of patients with CR-ECC isolates were retrospectively analyzed. Among the 108 CR-ECC isolates, 25 (23.2%) were non-susceptible to colistin, with colistin susceptibility being higher in <i>Enterobacter hormaechei</i> compared to non-<i>E</i>. <i>hormaechei</i> isolates (<i>P</i> < 0.0001). Of the 108 CR-ECC isolates, 9 (8.3%) produced carbapenemases, and only 6 of the 22 colistin-resistant CR-ECC isolates (27.3%) harbored the <i>mcr</i> gene. A total of 73 sequence types (STs), including 28 newly identified STs, were detected, demonstrating significant clonal diversity. The most common ST was ST74, known for its high prevalence and association with carbapenem resistance, with 77.8% identified as <i>E. hormaechei</i> subsp. <i>hoffmannii. E. hormaechei</i> was more common in the colistin-susceptible group than in the non-susceptible group (88.0% vs 37.5%, <i>P</i> < 0.0001), and <i>E. hormaechei</i> was the only protective factor for colistin resistance (HR 0.089, CI 0.030-0.261, <i>P</i> < 0.001). Although colistin resistance of CR-ECC is high, colistin could be administered safely to <i>E. hormaechei</i>. It is imperative to maintain ongoing surveillance and to further research on CR-ECC.IMPORTANCEAlthough new antibiotics are being developed, there are still limited options for treating carbapenem-resistant <i>Enterobacter cloacae</i> complex (CR-ECC) in regions where their use is restricted. The resistance level to one of these options, colistin, was investigated using bacteria isolated from clinical samples. In clinical practice, colistin is frequently administered empirically without susceptibility testing. However, this study suggests that colistin can be safely administered to certain species such as <i>Enterobacter hormaechei</i> within the CR-ECC.