Clonal and Horizontal Transmission of bla(NDM) among Klebsiella pneumoniae in Children’s Intensive Care Units

Increasing infections caused by bla(NDM)-carrying Klebsiella pneumoniae (NDM-KP) are an urgent threat to children with weakened immunity and limited antibiotic use. Preventing and intervening in NDM-KP infections requires a clear understanding of the pathogen’s molecular and epidemiological characteristics. We investigated the prevalence and characteristics of NDM-KP in six children’s hospitals from five Chinese provinces/municipalities. We collected 111 NDM-KP strains (40 NDM-1, one NDM-4 and 70 NDM-5) from neonatal intensive care units (NICUs) and pediatric intensive care units (PICUs) from June 2017 to June 2018; these strains accounted for 31.62% of all carbapenem-resistant K. pneumoniae (CR-KP). Although NDM-KP isolates exhibited high resistance to all carbapenems, including ertapenem (MIC: ≥32 mg/L, 96.4%), imipenem (MIC: ≥16 mg/L, 90.1%) and meropenem (MIC: ≥16 mg/L, 99.1%), they were fully sensitive to amikacin, tigecycline and polymyxin B, and presented low resistance to levofloxacin (9.9%) and gentamicin (15.3%). Whole-genome sequencing was conducted to gain insight into the molecular characterizations of NDM-KP isolates. The NDM-KP isolates belonged to 20 sequence types (STs), and ST2407 (n = 45) dominated in one hospital from Chengdu. ST2407 isolates with fewer single-nucleotide polymorphisms (SNP < 38) were found either in the same hospital or different hospitals. Most bla(NDM) (81.1%, 90/111), including all bla(NDM-5) and bla(NDM-4) and 47.5% (19/40) of bla(NDM-1), in NDM-KP isolates with 13 STs were associated with the IncX3 plasmid. Our results indicated that both explosive clonal transmission and horizontal transmission of bla(NDM) occur among NDM-KP strains in children's hospitals. These data provide a basis for preventing and controlling NDM-KP-associated infectious diseases in hospitalized children, especially in neonates. IMPORTANCE The bla(NDM) gene is playing an increasingly important role in infections caused by CR-KP, especially in children. However, systematic detection and bioinformatics analysis of NDM-KP in children's hospitals are lacking in China. In this study, a total of 111 NDM-positive K. pneumoniae isolates were selected from the China Antimicrobial Surveillance Network for further investigation. The isolates were further characterized using state-of-the-art molecular techniques. Our findings suggested the clonal and horizontal transmission of bla(NDM) in K. pneumoniae in NICUs/PICUs. Key plasmids (IncX3) and ST diversity contribute to the spread of bla(NDM). In addition, our findings provided recommendations for pediatric clinicians to use antibiotics to treat NDM-KP infections. Our current large-scale epidemiological survey would support further infection intervention strategies of NDM-KP in NICU/PICU of children's hospitals.