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

Abstract

Background. 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.Methods. Quarterly incidence of unique subjects (per 100 000 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.Results. Incidence of CRE clinical cultures among adult inpatients plateaued from 2013 (range: 7.73 to 10.32 per 100 000 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 bla KPC -positive, 97(31.6%) bla NDM -positive, and 42 (13.7%) bla OXA -positive. Klebsiella pneumoniae (n = 180, 41.9%), Escherichia coli (n = 129, 30.0%) and Enterobacter cloacae (n = 62, 14.4%) were the main Enterobacteriaceae species. WGS (n = 206) revealed diverse bacterial strain type (STs). The predominant bla KPC -positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant bla NDM -positive plasmid was pNDM-ECS01 (n = 46, 48.9%). Five transmission clusters involving 13 subjects were detected.Conclusions. 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.

Rapid Increase in Prevalence of Carbapenem-Resistant Enterobacteriaceae (CRE) and Emergence of Colistin Resistance Gene mcr-1 in CRE in a Hospital in Henan, China

“…During the 3-year surveillance period, high rates of carbapenem resistance and an increasing trend in the incidence of CRE in normally sterile site cultures, especially those caused by CRKP, were observed at Henan General Hospital. Rapid increases in the prevalence of CRE have been reported globally (8,9,19). In Singapore, a sharp increase in the incidence of clinical CRE infections was observed between 2010 and 2011, resulting mainly from a lack of proper intervention (early identification and spatial separation) (19).…”

“…Rapid increases in the prevalence of CRE have been reported globally (8,9,19). In Singapore, a sharp increase in the incidence of clinical CRE infections was observed between 2010 and 2011, resulting mainly from a lack of proper intervention (early identification and spatial separation) (19). A nationwide surveillance study of clinical CRE isolates in China from June 2014 to June 2015 indicated that 1.2 to 18.9% of K. pneumoniae isolates were resistant to carbapenems (20).…”

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae

“…All seven government-funded multidisciplinary hospitals in Singapore, which provide Ͼ80% of inpatient medical care in Singapore, participated in this network. Interim results and the methodology of the prospective CaPES study have previously been published and showed that all major genotypes of CPE were endemic in Singapore (22).…”

The role of hospital environment in transmissions of multidrug-resistant gram-negative organisms

“…Various mechanisms are involved in the development of carbapenem resistance depending on the bacterial species. However, since their discovery, carbapenemases (e.g., NDM, KPC, and OXA) have emerged as key drivers of carbapenem resistance across various Gram-negative bacterial species [2,3]. Lack of effective treatment and the consequent high mortality [4] has increased emphasis on the prevention of MDRGN transmission.…”