Pecora, N. D. | Search bioRxiv

bioRxiv2020

Genomic Characterization of Tissue Invasive Klebsiella pneumoniae Complex in a Hospital System with a Focus on Species Distribution and Hypervirulence

Klebsiella pneumoniae is an opportunistic pathogen known for multidrug resistance. Current research indicates that K. pneumoniae is a complex of closely related organisms (K. pneumoniae sensu stricto, K. quasipneumoniae, K. variicola, K. quasivariicola, and K. africana). Additionally, some strains of K. pneumoniae sensu stricto, known as hypervirulent K. pneumoniae (hvKp), cause severe infections in healthy members of the community. There is a paucity of research into rates of hvKp in the United States, the distribution of K. pneumoniae complex members in clinical specimens, and the pathogenic potential of complex members other than K. pneumoniae sensu stricto. We assessed the rates of hvKp and K. pneumoniae complex members in our 886 bed tertiary care facility in Rochester, New York. We performed whole genome sequencing on all inpatient, sterile-source isolates identified by routine culture work-up as K. pneumoniae from October 2018 - October 2019 (n=35). We additionally sequenced all K. pneumoniae liver isolates available in our collection, spanning 2017-2019 (n=18). In the yearlong collection of K. pneumoniae complex isolates, we found that 92.4% were K. pneumoniae sensu stricto (n=32), 5.7% were K. quasipneumoniae (n=2), and 2.9% were K. variicola (n=1). Five hvKp isolates were found, representing 5.7% (n=2) of K. pneumoniae sensu stricto isolates in the yearlong collection and 27.7% (n=5) of the liver isolate collection. All hvKp isolates were from liver; 60% were not associated with prior international residence.

microbiology↗

bioRxiv2018

Next-generation sequencing based hospital outbreak investigation yields insight into Klebsiella aerogenes population structure and determinants of carbapenem resistance and virulence

Klebsiella aerogenes is a nosocomial pathogen associated with drug resistance and outbreaks in intensive care units. In a 5-month period in 2017, we experienced an increased incidence of cultures for carbapenem-resistant K. aerogenes (CR-KA) from an adult cardiothoracic intensive care unit (CICU) involving 15 patients. Phylogenomic analysis following whole-genome sequencing (WGS) identified the outbreak CR-KA isolates to group together as a tight clonal cluster (<7 SNPs apart), suggestive of a protracted intra-ward transmission event. No clonal relationships were identified between the CICU CR-KA strains and additional hospital CR-KA patient isolates from different wards and/or previous years. Genes encoding carbapenemases or drug-resistant plasmids were absent in the outbreak strains, and carbapenem resistance was attributed to mutations impacting AmpD activity and membrane permeability. The CICU outbreak strains harbored an integrative conjugative element (ICEKp10), which has been associated with pathogenicity in hypervirulent Klebsiella pneumoniae lineages. Comparative genomics with global K. aerogenes genomes showed our outbreak strains to group closely with global ST4 strains, which along with ST93 likely represent dominant K. aerogenes lineages associated with human infections. WGS is a powerful tool that goes beyond high-resolution tracking of transmission events into identifying the genetic basis of drug-resistance and virulence, which are not part of conventional diagnostic workflows. With an increasing availability of sequenced genomes from across the globe, population structure analysis offers opportunities to identify emerging trends and dominant clones associated with specific syndromes and geographical locations for poorly characterized pathogens.

genomics↗