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

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Conflicts of Interest

Identified Weaknesses

Rating Explanation

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Paper Summary

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Sneaky Superbugs ST78 & ST133: Quietly Conquering Japanese Hospitals, Big & Small!

This study found that two types of highly drug-resistant bacteria (ST78 and ST133) are widespread in Japanese healthcare settings, including many small hospitals, suggesting a silent and ongoing clonal dissemination. The research used whole-genome sequencing of isolates collected across 58 hospitals, identifying ST133 as a particularly common and underreported lineage in Japan, emphasizing the need for broader molecular surveillance.

Possible Conflicts of Interest

M.O. and R.S. were employed by BML Inc. in Japan. The Biomedical Laboratories R&D Center, where clinical specimens were processed and initial antimicrobial susceptibility screening were performed, is listed. This constitutes a potential conflict of interest as employees of a company involved in data collection contributed to the study.

Identified Weaknesses

Limited Geographic Scope

The study did not include rare sequence types or isolates from the Kinki region (Osaka), where *bla*IMP-6 is prevalent, meaning the findings may not fully represent the entire country's epidemiology.

Absence of Patient-Level Clinical Data

Without patient-specific clinical information like movement between wards or clinical outcomes, the researchers could not differentiate between infection and colonization or reconstruct precise transmission pathways, limiting the depth of epidemiological analysis.

Restricted PCR Screening

PCR screening focused only on major carbapenemase genes, potentially missing uncommon variants or non-enzymatic resistance mechanisms (e.g., porin loss, AmpC overexpression), which could lead to an incomplete picture of resistance mechanisms.

Draft Genome Assembly Gaps

Using draft genome assemblies may have obscured certain genetic elements like specific antimicrobial resistance genes, mobile genetic elements, or plasmid replication genes, which are crucial for understanding resistance dynamics.

Sampling Bias

An overrepresentation of isolates from one high-burden facility and variable participation rates among hospitals could have introduced sampling bias, potentially affecting the observed distribution of sequence types and generalizability to the nationwide CPEC epidemiology.

Discordance Between Phenotypic and Genotypic Resistance

Some isolates carrying *bla*IMP-1 genes showed low meropenem MICs (phenotypic susceptibility), highlighting the challenge of relying solely on phenotypic screening and the need for molecular confirmation.

Rating Explanation

This is a strong study utilizing advanced genomic methods (WGS, cgMLST) to investigate an important public health issue of carbapenem-resistant bacteria in Japanese healthcare settings. It provides valuable insights into the clonal expansion and dissemination, particularly highlighting the underreported ST133 clone and spread in smaller hospitals. While some limitations and a potential conflict of interest were identified, they are well-acknowledged by the authors and do not significantly undermine the overall quality and findings of the research.

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