A high‐resolution genomic analysis of multidrug‐resistant hospital outbreaks of Klebsiella pneumoniae

摘要

AbstractMultidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity of K. pneumoniae in resource-poor hospital settings. Through whole-genome sequencing (WGS), we reconstructed an outbreak of MDR K. pneumoniae occurring on high-dependency wards in a hospital in Kathmandu during 2012 with a case-fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae. Using phylogenetic reconstruction and lineage-specific PCR, our data predicted a scenario in which K. pneumoniae, circulating for 6 months before the outbreak, underwent a series of ward-specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM-1 containing lineage in 2011 would have alerted the high-dependency ward staff to intervene. We argue that some form of real-time genetic characterisation, alongside clade-specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high- and low-income settings.SynopsisWhole-genome sequencing and further data analysis allowed for a comprehensive understanding of the emergence and spread of two highly virulent clones of drug-resistant Klebsiella pneumonia bloodstream infections from one hospital in Kathmandu, Nepal.MDR Klebsiella pneumoniae (Kp) can cause serious hospital outbreaks and can be associated with high mortality in hospitals in developing countries.Whole-genome sequencing (WGS) of Kp bloodstream infections was used to study localized transmission and genetic adaptation during a hospital outbreak in Nepal.Genetic material specific to outbreak lineages permitted a retrospective temporal reconstruction of two Kp outbreak lineages across the hospital.The added benefit of Kp WGS in this study was to dissect these outbreaks with extremely fine detail.Genetic characterization of Kp causing bloodstream infections in hospitals in developing countries should be performed routinely to identify and isolate outbreaks early.