Outbreak of NDM-5-producing Klebsiella pneumoniae ST307: an emerging high-risk antimicrobial resistance clone in Shanghai, China

Abstract

ABSTRACT The high-risk clone Klebsiella pneumoniae ST307, associated with various carbapenem resistance genes, exhibits a global distribution and prevalence. However, in China, it has remained sporadic and has rarely been detected. In this study, we reported an outbreak caused by nine ST307 CRKP isolates harboring bla NDM-5 in Shanghai, China, in 2022. We employed antimicrobial susceptibility testing, conjugation assay, whole-genome sequencing (WGS) and comparative genomics, phylogenetic analysis, and fitness and virulence comparison to further characterize the isolates causing the outbreak. Besides bla NDM-5 , these nine isolates co-carried bla CTX-M-15 and bla DHA-1 , exhibiting nearly identical resistance profiles with high-level resistance to carbapenems and ceftazidime/avibactam, while showing susceptibility to colistin and tigecycline. bla NDM-5 was located on an IncX3 plasmid of 45,403 bp with a high frequency of conjugative ability. Phylogenetic and single-nucleotide polymorphism (SNP) analysis indicated the nature of clonal transmission with a maximum of five SNPs between these nine isolates, and they were closely related to strains obtained from the United States. ST307 isolates in our study showed a relatively lower virulence but higher growth rates and certain adaptability compared with ST11 isolates. Clinical investigation revealed that shared nursing staff in a mixed emergency intensive care unit ward and doctors’ movement between wards might be responsible for the outbreak. The nonexistence before and sudden emergence of ST307 suggested that the currently circulating ST307 clone was a newly introduced superbug in our hospital. In conclusion, we revealed that bla NDM-5 -producing ST307 CRKP isolates, a globally significant high-risk clone, are spreading in China, posing a substantial threat to public health. IMPORTANCE The high-risk clone ST307, associated with various carbapenemases, including KPC, NDM, and OXA, has a global distribution. However, it is rarely reported in China, let alone causing outbreaks. Here, we found an outbreak caused by the clonal transmission of nine ST307 CRKP isolates. Clinical investigation revealed that shared nurses in a mixed emergency intensive care unit ward and doctors’ movement between wards might be responsible for the outbreak. In our study, the nine NDM-5-producing ST307 isolates exhibited high-level resistance to carbapenems and ceftazidime-avibactam, high conjugative ability to Escherichia coli J53, and certain adaptability to environment, phylogenetically closet to the United States. All these features make ST307 clone the next successful clone comparable to ST11 clone in China. Therefore, it is imperative for us to vigilantly monitor the prevalence of carbapenem-resistant Klebsiella pneumoniae and promptly implement measures to control the spread of K. pneumoniae ST307 in China.