title: Unnoticed spread of integron-carrying Enterobacteriaceae in intensive care units.
abstract: BACKGROUND
  Integrons are strongly associated with multidrug resistance in Enterobacteriaceae. Little is known about the natural history of integron-associated resistance in hospitals during nonoutbreak periods. The prevalence of integrons and the incidence of cross-transmission and horizontal gene transfer in Enterobacteriaceae with reduced susceptibility to cephalosporins (ERSC) were determined for 2 intensive care units (ICUs).
  
  
  METHODS
  Microbiological surveillance using rectal swab samples obtained 2 times per week and genotyping using amplified fragment-length polymorphism (AFLP) were used to determine colonization with and genetic relatedness of ERSC. IntI1 integrase polymerase chain reaction (PCR), conserved-segment PCR, restriction fragment-length polymorphism, and DNA sequencing were used to determine the prevalence and contents of integrons.
  
  
  RESULTS
  Of 457 patients, 121 patients were colonized with ERSC, and 174 isolates underwent AFLP and PCR. In 34 isolates obtained from 31 patients, 11 different integrons were identified; these integrons encoded resistance to streptomycin/spectinomycin, gentamicin/tobramycin/kanamycin, chloramphenicol, and trimethoprim. Integrons could be divided into 7 clusters of > or =2 isolates each. Compared with isolates that were negative for integrons, isolates that were positive for integrons were associated with resistance to piperacillin, cephalosporins, aminoglycosides, and quinolones. Acquisition rates of integron-carrying ERSC were 10 cases per 1000 patient-days in the first ICU and 8 cases per 1000 patient-days in the second ICU, with most cases (26 of 34) being acquired during the ICU stay. Nineteen episodes resulted from cross-transmission. In addition, 2 cases of interspecies transfer and 1 case of intraspecies transfer of integrons were recorded. Younger age was independently associated with acquisition of integron-carrying ERSC (hazard ratio, 0.953; 95% confidence interval, 0.926-0.987).
  
  
  CONCLUSIONS
  Surveillance, genotyping, and integron analysis identified previously unnoticed outbreaks of integron-carrying ERSC. Cross-transmission appeared to be the dominant route of transmission. Therefore, barrier precautions are necessary to prevent further spread.
authors.affiliation: Division of Acute Medicine and Infectious Diseases, University Medical Center Utrecht, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Nijssen
authors.forename: A
authors.initials: A
authors.lastname: Florijn
authors.forename: J
authors.initials: J
authors.lastname: Top
authors.forename: R
authors.initials: R
authors.lastname: Willems
authors.forename: A
authors.initials: A
authors.lastname: Fluit
authors.forename: M
authors.initials: M
authors.lastname: Bonten
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D003428:Cross Infection / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics; D004756:Enterobacteriaceae Infections / Q000453:epidemiology* / Q000382:microbiology / Q000635:transmission*; D005260:Female; D022761:Gene Transfer, Horizontal; D006801:Humans; D019426:Integrases; D032023:Integrons / Q000235:genetics*; D007362:Intensive Care Units; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D017422:Sequence Analysis, DNA
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D019426:Integrases; C115006:integron integrase IntI1