title: Clustering of antimicrobial resistance outbreaks across bacterial species in the intensive care unit.
abstract: BACKGROUND
  There are frequent reports of intensive care unit (ICU) outbreaks due to transmission of particular antibiotic-resistant bacteria. Less is known about the burden of outbreaks of resistance due to horizontal transfer of mobile genetic elements between species. Moreover, the potential of existing statistical software as a preliminary means for detecting such events has never been assessed. This study uses a software package to determine the burden of species and resistance outbreaks in 2 adjacent ICUs and to look for evidence of clustering of resistance outbreaks consistent with interspecies transmission of resistance elements.
  
  
  METHODS
  A retrospective analysis of data from 2 adjacent 15-bed adult ICUs between 2002 and 2009 was undertaken. Detection of bacterial species-groups and resistance outbreaks was conducted using SaTScan and WHONet-SaTScan software. Resampling and permutation methods were applied to investigate temporal clustering of outbreaks.
  
  
  RESULTS
  Outbreaks occurred for 69% of bacterial species-groups (18/26), and resistance outbreaks were detected against 63% of antibiotics (10/16). Resistance outbreaks against 7 of 10 antibiotics were observed in multiple species-groups simultaneously and there was evidence of inter-species-group dependence for 4 of 7 antibiotics; background temporal changes in resistance did not explain the temporal aggregation of outbreaks in 3 of 7 antibiotics.
  
  
  CONCLUSIONS
  Species outbreaks occurred for the majority of bacteria commonly identified in the ICU. There was evidence for frequent temporal clustering of resistance outbreaks consistent with interspecies transmission of resistance elements. Wider application of outbreak detection software combined with targeted sequencing of bacterial genomes is needed to understand the contribution of interspecies gene transfer to resistance emergence.
authors.affiliation: Centre for Clinical Infection and Diagnostics Research, Department of Infectious Diseases, King's College London and Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. a.vlek@umcutrecht.nl
authors.forename: Anne L M
authors.initials: AL
authors.lastname: Vlek
authors.forename: Ben S
authors.initials: BS
authors.lastname: Cooper
authors.forename: Theodore
authors.initials: T
authors.lastname: Kypraios
authors.forename: Andy
authors.initials: A
authors.lastname: Cox
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Edgeworth
authors.forename: Olga Tosas
authors.initials: OT
authors.lastname: Auguet
mesh_terms: D000328:Adult; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D001424:Bacterial Infections / Q000453:epidemiology*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D003428:Cross Infection / Q000453:epidemiology* / Q000382:microbiology; D004196:Disease Outbreaks; D024881:Drug Resistance, Bacterial; D006801:Humans; D007362:Intensive Care Units; D008826:Microbial Sensitivity Tests; D012189:Retrospective Studies; D012984:Software
keywords: antibiotic resistance; intensive care unit; outbreaks
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