Kalisvar Marimuthu1,2, Indumathi Venkatachalam3, Wei Xin Khong1, Tse Hsien Koh4, Benjamin Pei Zhi Cherng3, My Van La5, Partha Pratim De6,7, Prabha Unny Krishnan5,6,7, Thean Yen Tan8, Raymond Fong Kok Choon9, Surinder Kaur Pada10, Choong Weng Lam11, Say Tat Ooi12, Rama Narayana Deepak13, Nares Smitasin14, Eng Lee Tan15, Jia Jun Lee1, Asok Kurup16, Barnaby Young1, Nancy Tee Wen Sim17, Koh Cheng Thoon2,18, Dale Fisher2,14, Moi Lin Ling19, Brenda Ang Sze Peng1,7, Yik-Ying Teo20,21,22,23,24, Li Yang Hsu1,25, Raymond Tzer Pin Lin5,26, Rick Twee-Hee Ong20, Jeanette Teo26, Oon Tek Ng1,7. 1. Department of Infectious Diseases, Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, Singapore. 2. Yong Loo Lin School of Medicine, National University of Singapore. 3. Department of Infectious Diseases, Singapore General Hospital. 4. Department of Pathology, Singapore General Hospital. 5. National Public Health Laboratory, Ministry of Health of Singapore. 6. Department of Laboratory Medicine, Tan Tock Seng Hospital. 7. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore. 8. Department of Laboratory Medicine, Changi General Hospital, Singapore. 9. Division of Infectious Diseases, Department of Medicine, Changi General Hospital, Singapore. 10. Department of Infectious Diseases, Ng Teng Fong General Hospital, Singapore. 11. Department of Laboratory Medicine, Ng Teng Fong General Hospital, Singapore. 12. Department of Infectious Diseases, Khoo Teck Puat Hospital, Singapore. 13. Department of Laboratory Medicine, Khoo Teck Puat Hospital, Singapore. 14. Division of Infectious Diseases, National University Hospital, Singapore. 15. Centre of Biomedical and Life Sciences, Singapore Polytechnic. 16. Mount Elizabeth Hospital, Singapore. 17. Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore. 18. Department of Pediatrics, KK Women's and Children's Hospital, Singapore. 19. Department of Infection Prevention and Control, Singapore General Hospital. 20. Centre for Infectious Disease Epidemiology and Research, Saw Swee Hock School of Public Health, National University of Singapore. 21. NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Centre for Life Sciences (CeLS). 22. Department of Statistics & Applied Probability, Faculty of Science, National University of Singapore. 23. Life Sciences Institute, National University of Singapore. 24. Genome Institute of Singapore. 25. Saw Swee Hock School of Public Health, National University Health System. 26. Department of Laboratory Medicine, National University Hospital, 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 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. RESULTS: 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 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.
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 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. RESULTS: 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 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.
Authors: Ka Lip Chew; Michelle K L Tay; Bernadette Cheng; Raymond T P Lin; Sophie Octavia; Jeanette W P Teo Journal: Antimicrob Agents Chemother Date: 2018-07-27 Impact factor: 5.191
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