title: Antibiotic-Induced Within-Host Resistance Development of Gram-Negative Bacteria in Patients Receiving Selective Decontamination or Standard Care.
abstract: OBJECTIVE
  To quantify antibiotic-associated within-host antibiotic resistance acquisition rates in Pseudomonas aeruginosa, Klebsiella species, and Enterobacter species from lower respiratory tract samples of ICU patients receiving selective digestive decontamination, selective oropharyngeal decontamination, or standard care.
  
  
  METHODS
  Prospective cohort.
  
  
  METHODS
  This study was nested within a cluster-randomized crossover study of selective digestive decontamination and selective oropharyngeal decontamination in 16 ICUs in The Netherlands.
  
  
  METHODS
  Eligible patients were those colonized in the respiratory tract with P. aeruginosa, Klebsiella species, or Enterobacter species susceptible to one of the marker antibiotics and with at least two subsequent microbiological culture results from respiratory tract samples available.
  
  
  METHODS
  None.
  
  
  RESULTS
  Antibiotic resistance acquisition rates were defined as the number of conversions from susceptible to resistant for a specific antibiotic per 100 patient-days or 100 days of antibiotic exposure within an individual patient. The hazard of antibiotic use for resistance development in P. aeruginosa was based on time-dependent Cox regression analysis. Findings of this study cohort were compared with those of a previous cohort of patients not receiving selective digestive decontamination/selective oropharyngeal decontamination. Numbers of eligible patients were 277 for P. aeruginosa, 174 for Klebsiella species, and 106 for Enterobacter species. Resistance acquisition rates per 100 patient-days ranged from 0.2 (for colistin and ceftazidime in P. aeruginosa and for carbapenems in Klebsiella species) to 3.0 (for piperacillin-tazobactam in P. aeruginosa and Enterobacter species). For P. aeruginosa, the acquisition rates per 100 days of antibiotic exposure ranged from 1.4 for colistin to 4.9 for piperacillin-tazobactam. Acquisition rates were comparable for patients receiving selective digestive decontamination/selective oropharyngeal decontamination and those receiving standard care. Carbapenem exposure had the strongest association with resistance development (adjusted hazard ratio, 4.2; 95% CI, 1.1-15.6).
  
  
  CONCLUSIONS
  Within-host antibiotic resistance acquisition rates for systemically administered antibiotics were comparable between patients receiving selective decontamination and those receiving standard care and were highest during carbapenem use.
authors.affiliation: 1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 2Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. 3Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. 4Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 5Department of Intensive Care Medicine, Leiden University Medical Center, Leiden, The Netherlands. 6Department of Intensive Care, HagaZiekenhuis, The Hague, The Netherlands. 7Department of Intensive Care, Maastricht University Medical Centre, Maastricht, The Netherlands. 8Department of Intensive Care, Diakonessenhuis Utrecht, Utrecht, The Netherlands.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Noteboom
authors.forename: David S Y
authors.initials: DS
authors.lastname: Ong
authors.forename: Evelien A
authors.initials: EA
authors.lastname: Oostdijk
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: Evert
authors.initials: E
authors.lastname: de Jonge
authors.forename: Ilse
authors.initials: I
authors.lastname: Purmer
authors.forename: Dennis
authors.initials: D
authors.lastname: Bergmans
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Fijen
authors.forename: Jozef
authors.initials: J
authors.lastname: Kesecioglu
authors.forename: Marc J M
authors.initials: MJ
authors.lastname: Bonten
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D003422:Critical Care; D018592:Cross-Over Studies; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004754:Enterobacter / Q000187:drug effects; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006801:Humans; D007362:Intensive Care Units / Q000458:organization & administration*; D007709:Klebsiella / Q000187:drug effects; D009426:Netherlands / Q000453:epidemiology; D009960:Oropharynx / Q000187:drug effects / Q000382:microbiology; D011446:Prospective Studies; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012141:Respiratory Tract Infections / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents