Whole-genome sequence analysis of carbapenem-resistant Enterobacteriaceae recovered from hospitalized patients

Abstract

Carbapenems are among the few effective antibiotics against multidrug-resistant Enterobacteriaceae. This study aimed at characterizing the plasmid content and resistome of clinical carbapenem-resistant Enterobacteriaceae (CRE) recovered between 2016-2019 from hospitalized patients in Lebanon. Plasmid typing and whole-genome sequencing were used to study the genomic characteristics of 65 clinical CREs including 27 Escherichia coli, 24 Klebsiella pneumoniae, one Klebsiella quasipneumoniae, three Morganella morganii, three Citrobacter freundii, five Enterobacter hormaechei, and two Serratia marcescens. blaOXA-48 (33.8%; n=22) and blaOXA-48-like genes were among the detected resistance determinants, with two isolates co-harboring blaNDM-5. Various blaNDM variants, blaNDM-1 (16.9%; n=11), blaNDM-5 (9.2%; n=6), blaNDM-7 (9.2%; n=6), and blaNDM-19 (4.6%; n=3), different ESBLs and AmpC β-lactamases were detected. Carbapenem resistance determinants were linked a variety of incompatibility groups with IncFIB(K) (43.1%; n=28) being the most prevalent, followed by IncFIA (40.0%), IncL (35.4%), IncX3 (32.3%), IncI1 (32.3%), and IncFIIK (29.2%). We analyzed the clonality and resistance determinants of 65 multi-drug resistant (MDR) Enterobacteriaceae recovered in the period between 2016-2019 from a large tertiary hospital in Lebanon. NDM variants, OXA-48 and OXA-181were the most prevalent detected carbapenemases and were mostly linked to the dissemination of IncL, IncX3, and IncF. This study reinforces the need to track the spread and dominance of clinically relevant carbapenemase-encoding plasmids in healthcare settings.