Covert dissemination of carbapenemase-producing Klebsiella pneumoniae (KPC) in a successfully controlled outbreak: long and short-read whole-genome sequencing demonstrate multiple genetic modes of transmission

Journal article

Background

Carbapenemase-producing Enterobacteriaceae (CPE), including KPC-producing Klebsiella pneumoniae (KPC-Kpn), are an increasing threat to patient safety.

Objectives

To use whole-genome sequencing (WGS) to investigate the extent and complexity of carbapenemase gene dissemination in a controlled KPC outbreak.

Materials/methods

Enterobacteriaceae with reduced ertapenem susceptibility recovered from rectal screening swabs/clinical samples, during a three-month KPC outbreak (2013-14), were investigated for carbapenemase production, antimicrobial susceptibility, VNTR profile and WGS (short-read [Illumina], long-read [MinION]). Short-read sequences were used for MLST and plasmid/Tn4401 fingerprinting, and long-read sequence assemblies for plasmid identification. Phylogenetic analysis used IQTree followed by ClonalFrameML and outbreak transmission dynamics were inferred using SCOTTI.

Results

Twenty patients harboured KPC-positive isolates (6 infected, 14 colonised), and 23 distinct KPC-producing Enterobacteriaceae were identified. Four distinct KPC plasmids were characterised but of 20 KPC-Kpn (from six STs), 17 isolates shared a single pKpQIL-D2 KPC plasmid. All isolates had an identical transposon (Tn4401a), except one KPC-Kpn (ST661) with a single nucleotide variant. A sporadic case of KPC-Kpn(ST491) with Tn4401a-carrying pKpQIL-D2 plasmid was identified 10 months before the outbreak. This plasmid was later seen in two other species and other KPC-Kpn(ST14,ST661) including clonal spread of KPC-Kpn(ST661) from a symptomatic case to 9 ward contacts.

Conclusions

WGS of outbreak KPC isolates demonstrated blaKPC dissemination via horizontal transposition (Tn4401a), plasmid spread (pKpQIL-D2) and clonal spread (K. pneumoniae ST661). Despite rapid outbreak control, considerable dissemination of blaKPC still occurred among K. pneumoniae and other Enterobacteriaceae, emphasising its high transmission potential and the need for enhanced control efforts.

Authors: Martin, J; Phan, H; Findlay, J; Stoesser, N; Pankhurst, L

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Journal of Antimicrobial Chemotherapy
• Publication date: 2017-08-01
• Acceptance date: 2017-07-05
• DOI: 10.1093/jac/dkx264
• EISSN: 1520-5002
• ISSN: 0897-4756