Within-Ward Transmissions of Klebsiella pneumoniae Low-Endemic-Risk Clones Resolved by a Genomic Analysis: Highlighting the Role of Whole-Genome Sequencing in Infection Surveillance

Abstract

Background: K. pneumoniae can cause a wide range of diseases, and is highly associated with antimicrobial-resistant infections in hospitals. We aimed to characterize a five-year collection of K. pneumoniae genomes, and identify transmission events that were not identified by conventional typing approaches. \n \nMethods: From January 5, 2013 to July 24, 2018, 3,061 K. pneumoniae isolates were unbiasedly collected, and sequenced. The earliest strain recovered for each patient was retrospectively analyzed for the genomic epidemiology. Pairwise core-genome single-nucleotide polymorphism (cgSNP) distances were measured. An F1 score well differentiating isolates from the same ward and collected within 180 days was calculated. The best distance cutoffs, and the spatial-temporal information of each clone were combined to define transmission sub-lineages. \n \nFindings: A sum of 2,193 non-duplicated genomes was clustered into four species complexes. 93% (n = 2,035) was KpI with its largest clonal group being CG11 (20%, n = 406; 393 were ST11). 92% (n = 374) CG11 carried the carbapenem-resistant gene blaKPC-2. Four transmission sub- lineages (ST307-neo, ST20-neo, ST25-neo, and ST25-icu) were confidently identified by the integrated epidemiological-genomic method. None was from the high-endemic-risk clone CG11. \n \nInterpretation: Strain transmissions by low-endemic-risk clones are easy to be neglected by routine surveillance. Whole-genome sequencing analysis identified four episodes of within-ward transmissions of those neglectable clones: three in a neonatal ward, and one in ICU. Both wards are full of vulnerable patients. Thus, this study highlights the importance of including high-resolution typing technologies in infection surveillance, particularly for the neonates and critically-ill patients. \n \nFunding Information: This work was supported by National Natural Science Foundation of China [grant number 81672066 to WL]. This work was also supported by China National GeneBank (CNGB). \n \nDeclaration of Interests: We declare no competing interests. \n \nEthics Approval Statement: This study was approved by the ethics committees under tracking numbers 201806861 and BGI‐IRB 18061.