Emergence of a NDM-1-producing ST25 Klebsiella pneumoniae strain causing neonatal sepsis in China

Abstract

Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) seriously threaten the efficacy of modern medicine with a high associated mortality rate and unprecedented transmission rate. In this study, we isolated a clinical <i>K. pneumoniae</i> strain DY1928 harboring <i>bla</i> _NDM-1 from a neonate with blood infection. Antimicrobial susceptibility testing indicated that DY1928 was resistant to various antimicrobial agents, including meropenem, imipenem, ceftriaxone, cefotaxime, ceftazidime, cefepime, piperacillin-tazobactam, and amoxicillin-clavulanate. S1 nuclease-pulsed field gel electrophoresis (S1-PFGE), southern blot and conjugation experiment revealed that the <i>bla</i> _NDM-1 gene was located on a conjugative plasmid of IncA/C2 type with a 147.9 kb length. Whole-genome sequencing showed that there was a conservative structure sequence (<i>bla</i> _NDM-1-<i>ble</i>-<i>trpF</i>-<i>dsbD</i>) located downstream of the <i>bla</i> _NDM-1 gene. Multilocus sequence typing (MLST) classified DY1928 as ST25, which was a hypervirulent <i>K. pneumoniae</i> type. Phylogenetic analysis of genomic data from all ST25 <i>K. pneumoniae</i> strains available in the NCBI database suggested that all <i>bla</i> _NDM-1 positive strains were isolated in China and had clinical origins. A mouse bloodstream infection model was constructed to test the virulence of DY1928, and 11 <i>K. pneumoniae</i> strains homologous to DY1928 were isolated from the feces of infected mice. Moreover, we found that DY1928 had a tendency to flow from the blood into the intestine in mice and caused multiple organ damage. To our knowledge, this is the first study to report an infection caused by <i>bla</i> _NDM-1-positive ST25 <i>K. pneumoniae</i> in the neonatal unit. Our findings indicated that stricter surveillance and more effective actions were needed to reduce the risk of disseminating such <i>K. pneumoniae</i> strains in clinical settings, especially in neonatal wards.