Abstract
BackgroundKlebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extended-spectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. South and Southeast Asia are major hubs for antimicrobial-resistant (AMR) K. pneumoniae and also for the characteristically antimicrobial-sensitive, community-acquired “hypervirulent” strains. The emergence of hypervirulent AMR strains and lack of data on exopolysaccharide diversity pose a challenge for K. pneumoniae BSI control strategies worldwide.MethodsWe conducted a retrospective genomic epidemiology study of 365 BSI K. pneumoniae from seven major healthcare facilities across South and Southeast Asia, extracting clinically relevant information (AMR, virulence, K and O antigen loci) using Kleborate, a K. pneumoniae-specific genomic typing tool.ResultsK. pneumoniae BSI isolates were highly diverse, comprising 120 multi-locus sequence types (STs) and 63 K-loci. ESBL and carbapenemase gene frequencies were 47% and 17%, respectively. The aerobactin synthesis locus (iuc), associated with hypervirulence, was detected in 28% of isolates. Importantly, 7% of isolates harboured iuc plus ESBL and/or carbapenemase genes. The latter represent genotypic AMR-virulence convergence, which is generally considered a rare phenomenon but was particularly common among South Asian BSI (17%). Of greatest concern, we identified seven novel plasmids carrying both iuc and AMR genes, raising the prospect of co-transfer of these phenotypes among K. pneumoniae.ConclusionsK. pneumoniae BSI in South and Southeast Asia are caused by different STs from those predominating in other regions, and with higher frequency of acquired virulence determinants. K. pneumoniae carrying both iuc and AMR genes were also detected at higher rates than have been reported elsewhere. The study demonstrates how genomics-based surveillance—reporting full molecular profiles including STs, AMR, virulence and serotype locus information—can help standardise comparisons between sites and identify regional differences in pathogen populations.
Highlights
Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI)
The remaining isolates (Additional file 2: Table S2) were K. quasipneumoniae subsp. similipneumoniae (n = 20, 5·5%), K. variicola (n = 9, 2·5%) and K. quasipneumoniae subsp. quasipneumoniae (n = 5, 1·4%), which are indistinguishable from K. pneumoniae by microbiological methods [35, 67]
Acquired virulence determinants We identified genes linked to invasive disease: the yersiniabactin locus was present in 163 (49%) of the BSI K. pneumoniae, with the site prevalence ranging from 19 to 67% (Fig. 4a); no significant difference in ybt prevalence was observed between S and SE Asia (Table 1)
Summary
Klebsiella pneumoniae is a leading cause of bloodstream infection (BSI). Strains producing extendedspectrum beta-lactamases (ESBLs) or carbapenemases are considered global priority pathogens for which new treatment and prevention strategies are urgently required, due to severely limited therapeutic options. K. pneumoniae is highly diverse, hindering the development of such strategies and our ability to study its molecular epidemiology in a relevant time-frame This diverse bacterial species is generally associated with a range of differing community and healthcareassociated infections, but can be problematic when the organisms gain access to sterile sites such as the cerebrospinal fluid and the bloodstream. Such infections are often characterised by rapid onset and multidrug resistance (MDR), including resistance to thirdgeneration cephalosporins and/or carbapenems. Concomitant with this are elevated mortality rates and treatment costs [3]
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