Molecular epidemiology of Enterobacter cloacae complex isolates with reduced carbapenem susceptibility recovered by blood culture.

The Enterobacter cloacae complex (ECC) is one of the most common causes of bacteremia and leads to poor clinical outcomes. The aim of this study was to clarify the antimicrobial susceptibility profiles and genetic backgrounds of non-carbapenemase-producing reduced-carbapenem-susceptible (RCS) ECC blood isolates in Japan using agar dilution antimicrobial susceptibility testing, whole-genome sequencing, and quantitative polymerase chain reaction for assays of ampC, ompC and ompF transcripts. Forty-two ECC blood isolates were categorized into RCS and carbapenem-susceptible groups based on imipenem minimum inhibitory concentration. RCS ECC blood isolates belonged to distinct species and sequence types and produced varying class C β-lactamases. The E. roggenkampii, E. asburiae, and E. bugandensis isolates belonged only to the RCS group. Some E. hormaecheii ssp. steigerwaltii isolates of the RCS group exhibited AmpC overexpression caused by amino acid substitutions in AmpD and AmpR along with ompF gene downregulation. These findings suggest that non-carbapenemase-producing RCS ECC blood isolates are genetically diverse.