Next-Generation-Sequencing-Based Hospital Outbreak Investigation Yields Insight into Klebsiella aerogenes Population Structure and Determinants of Carbapenem Resistance and Pathogenicity

Abstract

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 monoclonal cluster (with no more than six single nucleotide polymorphisms [SNPs]), suggestive of a protracted intraward 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. Carbapenemase-encoding genes and 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 (ICE) which has been associated with pathogenic Klebsiella pneumoniae lineages (ICEKp10). Comparative genomics with global K. aerogenes genomes showed our outbreak strains to group closely with global sequence type 4 (ST4) strains, which, along with ST93, likely represent dominant K. aerogenes lineages associated with human infections. For poorly characterized pathogens, scaling analyses to include sequenced genomes from public databases offer the opportunity to identify emerging trends and dominant clones associated with specific attributes, syndromes, and geographical locations.

Emergence and Clonal Spread of KPC-2 Producing Clinical Klebsiella Aerogenes Isolates From a Teaching Hospital in Tucuman, Argentina.

“…According to the revision of clinical histories empirical antimicrobial treatments applied were poor due to multiple reasons: multi-resistance of the strains studied, medical personnel lack of knowledge of the magnitude of the outbreak and limited availability of other therapeutic options (tigecycline and fosfomycin) in the nosocomial pharmacy. These data are in line with Hao et al, who also identi ed the presence of severe disease and prior use of antimicrobials, primarily cephalosporins and quinolones, as risk factors associated to KPC-2 K. aerogenes infection 17 .…”

“…The average time of hospitalization was 16 days, patients were admitted in a range of 0-40 days previous to CRKA detection denoting the high hospital stay. The Intensive Care Unit was the most common site of acquisition, in line with previous reports [17][18][19] .…”

“…The soft tissue and the urinary tract (30%) were the most common sources of clinical samples, followed by abdominal liquid (20%), while other authors reported respiratory samples and blood as the prevalent clinical sources 17,20 .…”

<p>Carbapenem-Resistant <em>Klebsiella aerogenes</em> Clinical Isolates from a Teaching Hospital in Southwestern China: Detailed Molecular Epidemiology, Resistance Determinants, Risk Factors and Clinical Outcomes</p>

“…4 It is an important nosocomial pathogen associated with a wide variety of infections including pneumonia, bacteremia, urinary tract and surgical site infections. 5 Most importantly, K. aerogenes exhibited MDR phenotype during various hospital outbreaks. 5,6 Although K. aerogenes belongs to the family Enterobacteriaceae, its resistance mechanisms against carbapenems remain relatively unclear due to the limited amount of work performed to date in this field.…”

“…5 Most importantly, K. aerogenes exhibited MDR phenotype during various hospital outbreaks. 5,6 Although K. aerogenes belongs to the family Enterobacteriaceae, its resistance mechanisms against carbapenems remain relatively unclear due to the limited amount of work performed to date in this field. With the successive and increasing isolation of CRKA in our center in recent years, and the limited amount of work performed to date in CRKA, more attention has been evoking concerning its molecular epidemiology and carbapenemresistance mechanisms.…”