Genomic analysis of a pan-resistant Klebsiella pneumoniae sequence type 11 identified in Japan in 2016.

BACKGROUND

Klebsiella pneumoniae (K. pneumoniae) carbapenemase (KPC)-producing K. pneumoniae has rapidly expanded and is associated with severe nosocomial infections. Last-line antibiotics, such as colistin and tigecycline, remain the only treatment option. This study described the genetic background of a novel pan-resistant KPC-producing K. pneumoniae isolate from Tokyo, Japan.

METHODS

The antibiotic susceptibility of clinical isolates from a patient hospitalised in 2016 was tested using a MicroScan WalkAway instrument and the broth microdilution method. Susceptibility was defined according to breakpoints provided by the Clinical and Laboratory Standards Institute. Whole-genome sequencing was performed to detect acquired resistance genes and gene mutations.

RESULTS

The isolates were identified as part of a laboratory stool and swab surveillance-screening program for infection control. The carbapenem-resistant strain was resistant to β-lactams, including broad-spectrum cephalosporins and carbapenems, and to aminoglycosides, chloramphenicol, fosfomycin, fluoroquinolones, polymyxins, tetracyclines, and trimethoprim/sulfamethoxazole. The K. pneumoniae isolate harboured a plasmid carrying fosA3, rmtB, blaCTX-M-65, blaSHV-12, and blaKPC-2 in a non-Tn4401 mobile element. Colistin resistance was associated with a mutation in the mgrB gene, which regulates PhoP/PhoQ. The K. pneumoniae isolate belongs to sequence type 11, which is a successful epidemic-type strain.

CONCLUSION

This study identified molecular resistance markers in a pan-resistant isolate and provided a genomic description of the pan-resistance and origins of the isolate and plasmid. The isolate is closely related to a recent highly pathogenic carbapenem-resistant K. pneumoniae identified in China; however, it lacks a virulence plasmid (but it could still act as a reservoir for a virulence plasmid). This K. pneumoniae isolate is of concern in hospital and community care settings.