831. Analysis of a Worldwide Collection of Klebsiella pneumoniae CC258 with Reference to Carbapenemase Production Using the 1928 Core Genome (cg) Multilocus Sequence Type (MLST) Reveals Endemicity and Global Dissemination of Clones
Authors: Deshpande Lalitagauri M , Davis Andrew P , Dyrkell Fredrik , Arnellos Dimitrios , Castanheira Mariana 
Published: January 2021

Abstract

Background
K. pneumoniae (KPN) has emerged as a major hospital associated pathogen in the recent years. Clonal complex (CC) 258 constitutes an international epidemic clone responsible for spread of extended spectrum beta-lactamases (ESBL) and carbapenemases. We evaluated the core genome (cg) MLST, resistance (R) gene and plasmid profiles of a worldwide collection of KPN using the 1928 bioinformatic cloud platform.

Methods
A total of 155 KPN clinical isolates (CC258, n=129; non-CC258, n=26) collected from 19 countries during 2018 of SENTRY Program were analyzed. Isolates included carbapenem resistant (CR; n=120) and non-CR (n=35). Whole genome sequencing FASTQ files were uploaded to the 1928 pipeline for analysis.

Results
Most CC258 isolates belonged to ST258, ST11 and ST512 (Table), and separated from unrelated ST by allelic distance (ad) &gt; 2000. cgMLST grouped together isolates from the same STs, and those from similar geographies had greater homology, except isolates from US showed greater heterogenicity (ad 620). Applying an ad cutoff of &lt; 100, ST258 isolates grouped in 4 clades with a predominance of either KPC-2 or -3. An ad cutoff of &lt; 200 identified 7 clades within ST11 that were related by geography and R genes. Among CC258 isolates KPC was the major carbapenemase (58.1%) and associated with Tn4401 (a or b in 84% KPC); NDM-1 was detected (8.5%) only in ST11 and ST395. KPC-2 was more prevalent in Latin America and the isolates were closely related (ad 104) among ST258 compared to ST11 (ad 355). KPC-3 CC258 isolates showed ad of 164 and were from Italy, Russia, Greece, and US. CTX-M-14 was prevalent in ST258 while CTX-M-15 was common in other STs, except ST512 which carried no CTX-M despite clustering within ST258.

Conclusion
1928 generated cgMLST showed good correlation with MLST in classifying all KPN isolates. ST258 isolates showed tight clustering, no NDM genes and distribution in the Americas while ST11 showed global dissemination and diversity of carbapenemases.
Table 1

Disclosures
Fredrik Dyrkell, n/a, 1928 Diagnostics (Employee) Dimitrios Arnellos, n/a, 1928 Diagnostics (Employee) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support)