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

• Published in: Clinical infectious diseases Vol. 64; no. suppl_2; pp. S68 - S75
• Main Authors: Marimuthu, Kalisvar, Venkatachalam, Indumathi, Khong, Wei Xin, Koh, Tse Hsien, Cherng, Benjamin Pei Zhi, Van La, My, De, Partha Pratim, Krishnan, Prabha Unny, Tan, Thean Yen, Choon, Raymond Fong Kok, Pada, Surinder Kaur, Lam, Choong Weng, Ooi, Say Tat, Deepak, Rama Narayana, Smitasin, Nares, Tan, Eng Lee, Lee, Jia Jun, Kurup, Asok, Young, Barnaby, Sim, Nancy Tee Wen, Thoon, Koh Cheng, Fisher, Dale, Ling, Moi Lin, Peng, Brenda Ang Sze, Teo, Yik-Ying, Hsu, Li Yang, Lin, Raymond Tzer Pin, Ong, Rick Twee-Hee, Teo, Jeanette, Ng, Oon Tek
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.05.2017
• Subjects: Adult; Aged; Anti-Bacterial Agents - therapeutic use; Antibiotics; Bacteria; beta-Lactam Resistance; beta-Lactamases - biosynthesis; beta-Lactamases - genetics; Carbapenem-Resistant Enterobacteriaceae - drug effects; Carbapenem-Resistant Enterobacteriaceae - genetics; Carbapenem-Resistant Enterobacteriaceae - isolation & purification; Carbapenemase; Carbapenems - pharmacology; Carbapenems - therapeutic use; Clusters; Cross Infection - epidemiology; Disease transmission; DNA, Bacterial - genetics; E coli; Electronic Health Records; Electronic medical records; Enterobacter cloacae; Enterobacter cloacae - genetics; Enterobacter cloacae - isolation & purification; Enterobacteriaceae Infections - epidemiology; Enterobacteriaceae Infections - microbiology; Enterobacteriaceae Infections - transmission; Epidemiology; Escherichia coli - genetics; Escherichia coli - isolation & purification; Escherichia coli Infections - epidemiology; Female; Gene sequencing; Genome, Bacterial; Genomes; High-Throughput Nucleotide Sequencing; Hospitals; Humans; Incidence; Indexing; Inpatients; Klebsiella; Klebsiella Infections - epidemiology; Klebsiella pneumoniae - genetics; Klebsiella pneumoniae - isolation & purification; Male; Multivariate analysis; Plasmids; Public health; Surveys and Questionnaires; Young Adult; Singapore; carbapenem-resistant Enterobacteriaceae; epidemiology; antimicrobial resistance; whole-genome sequencing
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1093/cid/cix113

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 blaKPC-positive, 97(31.6%) blaNDM-positive, and 42 (13.7%) blaOXA-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 blaKPC-positive plasmid was pHS102707 (n = 62, 55.4%) and the predominant blaNDM-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.