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

Abstract

Carbapenem-resistant Enterobacter cloacae 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 hsp60 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 Enterobacter hormaechei compared to non-E. hormaechei isolates (P < 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 mcr 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 E. hormaechei subsp. hoffmannii. E. hormaechei was more common in the colistin-susceptible group than in the non-susceptible group (88.0% vs 37.5%, P < 0.0001), and E. hormaechei was the only protective factor for colistin resistance (HR 0.089, CI 0.030-0.261, P < 0.001). Although colistin resistance of CR-ECC is high, colistin could be administered safely to E. hormaechei. 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 Enterobacter cloacae 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 Enterobacter hormaechei within the CR-ECC.

Keywords: Enterobacter cloacae complex; antibiotic resistance; carbapenem; colistin; molecular epidemiology.

Fig 1

Multilocus sequence typing with minimum spanning tree of 108 clinical isolates of carbapenem-resistant Enterobacter cloacae complex. Phylogenetic tree based on neighbor-joining method using hsp60 gene sequences of 108 clinical isolates and reference strains of Enterobacter cloacae complex. Species based on the partial hsp60 sequences are shown in different colors. Each node within the tree represents a single ST, and the length of branches between each node represents the number of different alleles.