title: Dynamics of MDR Enterobacter cloacae outbreaks in a neonatal unit in Nepal: insights using wider sampling frames and next-generation sequencing.
abstract: OBJECTIVE
  There are limited data on Enterobacter cloacae outbreaks and fewer describing these in association with NDM-1. With whole-genome sequencing, we tested the hypothesis that a cluster of 16 E. cloacae bacteraemia cases in a Nepali neonatal unit represented a single clonal outbreak, using a wider set of epidemiologically unrelated clinical E. cloacae isolates for comparison.
  
  
  METHODS
  Forty-three isolates were analysed, including 23 E. cloacae and 3 Citrobacter sp. isolates obtained from blood cultures from 16 neonates over a 3 month period. These were compared with two contemporaneous community-associated drug-resistant isolates from adults, a unit soap dispenser isolate and a set of historical invasive isolates (n=14) from the same geographical locality.
  
  
  RESULTS
  There were two clear neonatal outbreaks and one isolated case in the unit. One outbreak was associated with an NDM-1 plasmid also identified in a historical community-associated strain. The smaller, second outbreak was likely associated with a contaminated soap dispenser. The two community-acquired adult cases and three sets of historical hospital-associated neonatal isolates represented four additional genetic clusters.
  
  
  CONCLUSIONS
  E. cloacae infections in this context represent several different transmission networks, operating at the community/hospital and host strain/plasmid levels. Wide sampling frames and high-resolution typing methods are needed to describe the complex molecular epidemiology of E. cloacae outbreaks, which is not appropriately reflected by routine susceptibility phenotypes. Soap dispensers may represent a reservoir for E. cloacae and bacterial strains and plasmids may persist in hospitals and in the community for long periods, sporadically being involved in outbreaks of disease.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK nicole.stoesser@ndm.ox.ac.uk.
authors.forename: N
authors.initials: N
authors.lastname: Stoesser
authors.affiliation: NIHR Biomedical Research Centre, University of Oxford/Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: A E
authors.initials: AE
authors.lastname: Sheppard
authors.affiliation: Department of Paediatrics, Patan Hospital, Kathmandu, Nepal.
authors.forename: M
authors.initials: M
authors.lastname: Shakya
authors.affiliation: Department of Paediatrics, Patan Hospital, Kathmandu, Nepal.
authors.forename: B
authors.initials: B
authors.lastname: Sthapit
authors.affiliation: Department of Paediatrics, Patan Hospital, Kathmandu, Nepal.
authors.forename: S
authors.initials: S
authors.lastname: Thorson
authors.affiliation: NIHR Biomedical Research Centre, University of Oxford/Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: A
authors.initials: A
authors.lastname: Giess
authors.affiliation: NIHR Biomedical Research Centre, University of Oxford/Oxford University Hospitals NHS Trust, Oxford, UK Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Kelly
authors.affiliation: NIHR Biomedical Research Centre, University of Oxford/Oxford University Hospitals NHS Trust, Oxford, UK Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Pollard
authors.affiliation: NIHR Biomedical Research Centre, University of Oxford/Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: T E A
authors.initials: TE
authors.lastname: Peto
authors.affiliation: NIHR Biomedical Research Centre, University of Oxford/Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: A S
authors.initials: AS
authors.lastname: Walker
authors.affiliation: NIHR Biomedical Research Centre, University of Oxford/Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: D W
authors.initials: DW
authors.lastname: Crook
mesh_terms: D000328:Adult; D016470:Bacteremia / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D001769:Blood / Q000382:microbiology; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004196:Disease Outbreaks; D018562:Disease Transmission, Infectious; D016972:Enterobacter cloacae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D004756:Enterobacteriaceae Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission; D004783:Environmental Microbiology; D016680:Genome, Bacterial; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009390:Nepal / Q000453:epidemiology; D012189:Retrospective Studies
chemical_list: D004269:DNA, Bacterial
keywords: NDM; carbapenemases; epidemiology; whole-genome sequencing