Clinical and Molecular Epidemiology of Carbapenem-Resistant Enterobacteriaceae Among Adult Inpatients in Singapore

<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background.</div>Since 2010, the incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing in Singapore. We analyzed the clinical and molecular epidemiology of CRE among adult inpatients in Singapore.<div class="boxTitle">Methods.</div>Quarterly incidence of unique subjects (per 100000 patient-days) with positive clinical and surveillance cultures for CRE were estimated based on mandatory data submitted to the National Public Health Laboratory by public hospitals between 2010 and 2015. CRE-positive adult inpatients were prospectively recruited from 6 public sector hospitals between December 2013 and April 2015. Subjects answered a standardized epidemiologic questionnaire and provided samples for this study. Further clinical information was extracted from subjects' electronic medical records. Whole-genome sequencing was performed on study isolates to determine transmission clusters.<div class="boxTitle">Results.</div>Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100000 patient-days) following an initial increase between 2010 and end-2012. We prospectively recruited 249 subjects. Their median age was 65 years, 108 (43%) were female, and 161 (64.7%) had carbapenemase-producing Enterobacteriaceae (CPE). On multivariate analysis, prior carbapenem exposure (OR: 3.23; 95% CI: 1.67–6.25) and hematological malignancies (OR: 2.85; 95% CI: 1.10–7.41) were associated with non-carbapenemase-producing CRE (NCPE) (n = 88) compared with CPE (n = 161) subjects. Among 430 CRE isolates from the 249 subjects, 307(71.3%) were CPE, of which 154(50.2%) were <span style="font-style:italic;">bla</span>_KPC-positive, 97(31.6%) <span style="font-style:italic;">bla</span>_NDM-positive, and 42 (13.7%) <span style="font-style:italic;">bla</span>_OXA-positive. <span style="font-style:italic;">Klebsiella pneumoniae</span> (n = 180, 41.9%), <span style="font-style:italic;">Escherichia coli</span> (n = 129, 30.0%) and <span style="font-style:italic;">Enterobacter cloacae</span> (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant <span style="font-style:italic;">bla</span>_KPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant <span style="font-style:italic;">bla</span>_NDM-positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five transmission clusters involving 13 subjects were detected.<div class="boxTitle">Conclusions.</div>Clinical CRE trend among adult inpatients showed stabilization following a rapid rise since introduction in 2010 potentially due to infection prevention measures and antimicrobial stewardship. More work is needed on understanding CPE transmission dynamics.</span>

http://ift.tt/2pqK9fv