Abstract
Whole genome sequencing was used to characterize the resistome of intensive care unit (ICU) outbreak-associated carbapenem-resistant K. pneumoniae isolates. Importantly, and of particular concern, the carbapenem-hydrolyzing β-lactamase gene bla OXA-48 and the extended-spectrum β-lactamase gene bla CTX-M-14, were identified on a single broad host-range conjugative plasmid. This represents the first report of bla OXA-48 in Australia and highlights the importance of resistance gene surveillance, as such plasmids can silently spread amongst enterobacterial populations and have the potential to drastically limit treatment options. Furthermore, the in vivo evolution of these isolates was also examined after 18 months of intra-abdominal carriage in a patient that transited through the ICU during the outbreak period. Reflecting the clonality of K. pneumoniae, only 11 single nucleotide polymorphisms (SNPs) were accumulated during this time-period and many of these were associated with genes involved in tolerance/resistance to antibiotics, metals or organic solvents, and transcriptional regulation. Collectively, these SNPs are likely to be associated with changes in virulence (at least to some extent) that have refined the in vivo colonization capacity of the original outbreak isolate.
Highlights
Klebsiella pneumoniae is a common cause of infections worldwide, both in community and hospital settings [1,2]
With respect to Enterobacteriaceae, Ambler class D carbapenem-hydrolyzing b-lactamase (CHDL) genes have recently emerged in Australia with the report of a clinical K. pneumoniae isolate carrying a plasmid with blaOXA-181 [9]
A related gene, blaOXA-48, which was first identified in a K. pneumoniae isolate from Turkey in 2001 [10], and that has spread to Africa, Asia and Europe, has not previously been detected in Australia [11]
Summary
Klebsiella pneumoniae is a common cause of infections worldwide, both in community and hospital settings [1,2]. Based on data from the Study for Monitoring Antimicrobial Resistance Trends (SMART), carbapenems remain the most effective treatment option for these infections, especially those caused by strains producing extended-spectrum b-lactamases (ESBLs) [1,2]. In Australia, carbapenem resistance in K. pneumoniae is uncommon and over the past decade has generally been secondary to the expression of metallo-b-lactamase (MBL) genes ( blaIMP-4) [6], in combination with changes in outer-membrane porins. Two K. pneumoniae isolates have been reported that produce either the MBL NDM-1 [7] or an Ambler Class A KPCtype carbapenem-hydrolyzing b-lactamase [8]. With respect to Enterobacteriaceae, Ambler class D carbapenem-hydrolyzing b-lactamase (CHDL) genes have recently emerged in Australia with the report of a clinical K. pneumoniae isolate carrying a plasmid with blaOXA-181 [9]. The broad dissemination of blaOXA-48, which has largely been due to an association with plasmid-borne Tn1999 or related transposons [11], is of major concern given the ease at which transmission and spread occurs and the subsequent consequence for therapy
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