High-risk clonal expansion of IMP-producing Enterobacter cloacae complex in regional Japanese healthcare settings

Carbapenemase-producing Enterobacter cloacae complex (CPEC) represents an emerging threat in healthcare settings; however, its spread across local and regional hospitals remains elusive. Between 2014 and 2022, 211 non-duplicate E. cloacae complex isolates (ECC) with reduced carbapenem susceptibility based on automated susceptibility testing were collected from 58 hospitals in 14 prefectures across Japan. PCR detected the bla_IMP-1 group in 92.9% of isolates. Among these, 80 representative CPEC isolates underwent whole-genome sequencing. Two dominant high-risk clonal groups, ST78 and ST133 (including single-locus variants), accounted for 62.5% of sequenced isolates. Notably, ST133-rarely reported in Japan-was the second most common type and detected widely, suggesting gradual and inconspicuous dissemination. ST78 exhibited substantial genomic diversity, frequent co-carriage of extended-spectrum beta-lactamase genes, and multiple plasmid replicons, while ST133 formed a more uniform lineage with limited resistance determinants. Most isolates remained highly susceptible to amikacin and cefiderocol. Core-genome multi-locus sequence typing suggested possible intra-facility persistence and inter-facility transmission of closely related strains (≤10 allele differences) in some hospitals over time. Among the 46 facilities with bla_IMP-1 group-positive isolates, 73.9% (34/46) were small hospitals (<200 beds). The proportion among screened ECC isolates was similarly high in small and large hospitals (90.5% vs 94.8%), with no significant difference, suggesting the need to extend molecular surveillance even in resource-limited settings. These findings highlight the utility of molecular confirmation and targeted genomic analysis, particularly in regions or settings where high-risk CPEC clones may circulate undetected, to support timely detection and containment efforts.