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

Clin Infect Dis. 2017 May 15;64(suppl_2):S68-S75. doi: 10.1093/cid/cix113.

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.

Keywords: antimicrobial resistance.; carbapenem-resistant Enterobacteriaceae; epidemiology; whole-genome sequencing.

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / therapeutic use
  • Carbapenem-Resistant Enterobacteriaceae / drug effects
  • Carbapenem-Resistant Enterobacteriaceae / genetics*
  • Carbapenem-Resistant Enterobacteriaceae / isolation & purification
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use
  • Cross Infection / epidemiology*
  • DNA, Bacterial / genetics
  • Electronic Health Records
  • Enterobacter cloacae / genetics
  • Enterobacter cloacae / isolation & purification
  • Enterobacteriaceae Infections / epidemiology*
  • Enterobacteriaceae Infections / microbiology
  • Enterobacteriaceae Infections / transmission
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification
  • Escherichia coli Infections / epidemiology
  • Female
  • Genome, Bacterial
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Incidence
  • Inpatients*
  • Klebsiella Infections / epidemiology
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / isolation & purification
  • Male
  • Surveys and Questionnaires
  • Young Adult
  • beta-Lactam Resistance
  • beta-Lactamases / biosynthesis
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • DNA, Bacterial
  • beta-Lactamases