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

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.