title: Decolonization of intestinal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae with oral colistin and neomycin: a randomized, double-blind, placebo-controlled trial.
abstract: OBJECTIVE
  Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are an increasingly frequent cause of infections in the community and the healthcare setting. In this study, we aimed to investigate whether intestinal carriage of ESBL-E can be eradicated.
  
  
  METHODS
  We conducted a double-blind, randomized, placebo-controlled, single-centre trial to assess the efficacy of an oral decolonization regimen on intestinal ESBL-E carriage in adult patients with an ESBL-E-positive rectal swab. Fifty-eight patients were allocated 1 : 1 to either placebo or colistin sulphate (50 mg 4×/day) and neomycin sulphate (250 mg 4×/day) for 10 days plus nitrofurantoin (100 mg 3×/day) for 5 days in the presence of ESBL-E bacteriuria. The primary outcome was detection of ESBL-E by rectal swab 28 ± 7 days after the end of treatment. Missing primary outcome data were imputed based on the last available observation. Additional cultures (rectal, inguinal and urine) were taken on day 6 of treatment and on days 1 and 7 post-treatment. The study protocol has been registered with ClinicalTrials.gov (NCT00826670).
  
  
  RESULTS
  Among 54 patients (27 in each group) included in the primary analysis, there was no statistically significant difference between the groups with regard to the primary outcome [14/27 (52%) versus 10/27 (37%), P = 0.27]. During treatment and shortly afterwards, there was significantly lower rectal ESBL-E carriage in the treatment group: 9/26 versus 19/22 on day 6 of treatment (P < 0.001) and 8/25 versus 20/26 on day 1 post-treatment (P = 0.001). This effect had disappeared by day 7 post-treatment (18/27 versus 17/25, P = 0.92). Liquid stools were more common in the treatment group (7/27 versus 2/29, P = 0.05).
  
  
  CONCLUSIONS
  The regimen used in this study temporarily suppressed ESBL-E carriage, but had no long-term effect.
authors.affiliation: Infection Control Program, Geneva University Hospital and Faculty of Medicine, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 4, Switzerland.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Huttner
authors.forename: Thomas
authors.initials: T
authors.lastname: Haustein
authors.forename: Ilker
authors.initials: I
authors.lastname: Uçkay
authors.forename: Gesuele
authors.initials: G
authors.lastname: Renzi
authors.forename: Andrew
authors.initials: A
authors.lastname: Stewardson
authors.forename: Danièle
authors.initials: D
authors.lastname: Schaerrer
authors.forename: Americo
authors.initials: A
authors.lastname: Agostinho
authors.forename: Antoine
authors.initials: A
authors.lastname: Andremont
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
authors.forename: Didier
authors.initials: D
authors.lastname: Pittet
authors.forename: Stephan
authors.initials: S
authors.lastname: Harbarth
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002353:Carrier State / Q000188:drug therapy* / Q000382:microbiology; D003091:Colistin / Q000627:therapeutic use*; D004311:Double-Blind Method; D004755:Enterobacteriaceae / Q000201:enzymology*; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D005601:Framycetin / Q000627:therapeutic use*; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D010919:Placebos; D005601:Framycetin; C488396:neamine; D001618:beta-Lactamases; D003091:Colistin
keywords: Switzerland; aminoglycosides; multidrug-resistant organisms; nitrofurantoin; polymyxins