Genomic Insights Into the Mechanism of Carbapenem Resistance Dissemination in Enterobacterales From a Tertiary Public Heath Setting in South Asia

Abstract

Background Given the high prevalence of multidrug resistance (MDR) across South Asian (SA) hospitals, we documented the epidemiology of carbapenem resistant Enterobacterales (CRE) infections at Dhaka Medical College Hospital between October 2016 to September 2017. Methods We enrolled patients and collected epidemiology and outcome data. All Enterobacterales were characterised phenotypically and by whole genome sequencing. Risk assessment for the patients with CRE were performed compared to patients with carbapenem-susceptible Enterobacterales (CSE). Results 10.6% of all 1831 patients with a clinical specimen collected had CRE. In-hospital 30-day mortality was significantly higher with CRE [50/180 (27.8%)] than CSE [42/312 (13.5%)] (p = 0.001); however, for blood-stream infections, this was insignificant. Out of 643 Enterobacterales isolated, 210 were CRE. blaNDM was present in 180 isolates, blaOXA-232 in 26, blaOXA-181 in 24 and blaKPC-2 in 5. Despite this, ceftriaxone was the most commonly prescribed empirical antibiotic and only 27% patients were prescribed at least one antibiotic to which their infecting pathogen was susceptible. Significant risk factors for CRE isolation included burns unit and ICU admission, and prior exposure to levofloxacin, amikacin, clindamycin and meropenem. E. coli ST167 was the dominant CRE clone. Clustering suggested clonal transmission of K. pneumoniae ST15 and the MDR hyper-virulent clone, ST23. The major trajectories involved in horizontal gene transfer were IncFII and IncX3, IS26, and Tn3. Conclusion This is the largest study from a SA public hospital combining outcome, microbiology and genomics. The findings indicate the urgent implementation of targeted diagnostics, appropriate antibiotic use and infection control interventions in SA public institutions.

Genomic Characterization of an Extensively Drug-Resistant Extra-Intestinal Pathogenic (ExPEC) Escherichia coli Clinical Isolate Co-Producing Two Carbapenemases and a 16S rRNA Methylase

“…Plasmid p1606A encoded multidrug resistance including all β-lactams (except aztreonam), aminoglycosides, sulfonamides, and tetracycline, since it harbored the bla NDM-5 , rmtB , aadA5 , dfrA17 , tet(A), bla TEM-1B , sul1 , and qacE resistance genes. The sequence of plasmid p1606A analyzed by using the Basic Local Alignment Search Tool (BLAST) provided by NCBI was highly similar to that of other bla NDM-5 -positive IncF-type plasmids, namely p_dm702b_NDM5 (99% query coverage and 99.99% sequence identity; GenBank accession number CP095643), p_dm708c_NDM5 (99% query coverage and 99.97% sequence identity; GenBank accession number CP095644), and p_dm566_NDM5 (99% query coverage and 99.97% sequence identity; GenBank accession number CP095630) recently identified from E. coli isolates recovered in Bangladesh [ 33 ]. The bla KPC-3 -carrying plasmid, namely p1606B, was 53,292 bp in size and belonged to the IncX3 incompatibility group, with bla KPC-3 being located into transposon Tn 4401 (△IS 3000-tnpR-tnpA- IS Kpn7-bla KPC-3 -tnpA- IS Kpn6- △IS 3000 ), similarly to the structure identified on the KPC-3-IncX3 plasmid pCfr-145 (KY659388) recently identified among Citrobacter freundii isolates in Italy [ 34 , 35 , 36 ].…”

Emergence of an IncX3 plasmid co-harbouring the carbapenemase genes blaNDM-5 and blaOXA-181

“…An isolate co-carrying bla NDM-5 and bla OXA-181 , JBEHAAB-19-0176, was obtained from the faeces of an outpatient who had returned from a trip to Bangladesh and was diagnosed with Campylobacter enteritis. These carbapenemase genes are the most common and the third most common carbapenemase genes encountered in a hospital surveillance in Bangladesh, respectively; 22 however, both genes have rarely been detected in Japan. 12 Therefore, it is likely that the isolate was imported from Bangladesh.…”

Molecular Characterization of Escherichia coli Causing Urinary Tract Infections Through Next-Generation Sequencing: A Comprehensive Analysis of Serotypes, Sequence Types, and Antimicrobial and Virulence Genes

“…Escherichia coli ST-167 was identified as a predominant clone that carried carbapenem resistance through conjugative plasmids ( IncFII and IncX3 , IS26 , and Tn3 ) that can potentially contribute to horizontal gene transfer [ 35 ]. More numbers (12/50, 24%) of E .…”