title: Bacteria with increased mutation frequency and antibiotic resistance are enriched in the commensal flora of patients with high antibiotic usage.
abstract: BACKGROUND
  We examined how prolonged antibiotic treatment affected the resistance and mutation frequency of human microflora isolated from intestine (Escherichia coli, enterococci spp.), pharynx (alpha-streptococci) and nostril (coagulase-negative staphylococci, CoNS).
  
  
  METHODS
  Samples were collected from patients at the Center of Cystic Fibrosis (n=18) and the haematology ward (n=18) of the University Hospital, Uppsala, Sweden. The individually used amount of antibiotics for 1 year was recorded as the defined daily dose (DDD). Primary health care patients (n=30), with no antibiotic treatment for 1 year before sampling, were used as controls. Three isolates of each bacterium from each patient were examined. Antibiotic susceptibilities were determined by disc diffusion. Mutation frequencies to rifampicin resistance were measured on 30 independent cultures of each bacterial species from each individual by plating on rifampicin agar plates. For alpha-streptococci the mutation frequency to streptomycin resistance was also determined.
  
  
  RESULTS
  Isolates from patients with high antibiotic use showed a pronounced shift towards increased resistance and a small but significant increase in the mutation frequency compared with isolates from the controls. For E. coli, enterococci and CoNS the increase in geometric mean mutation frequency in the patient group was 3-, 1.8- and 1.5-fold, respectively (P values 0.0001, 0.016 and 0.012). For alpha-streptococci there was a significant difference in geometric mean mutation frequency between patient and control groups for streptomycin resistance (P=0.024) but not for rifampicin resistance (P=0.74).
  
  
  CONCLUSIONS
  High antibiotic use selected for commensals with highly increased resistance and a slight increase in mutation frequency.
authors.affiliation: Antibiotic Research Unit, Department of Medical Sciences, Section of Clinical Bacteriology, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Ingegerd
authors.initials: I
authors.lastname: Gustafsson
authors.forename: Maria
authors.initials: M
authors.lastname: Sjölund
authors.forename: Erik
authors.initials: E
authors.lastname: Torell
authors.forename: Marie
authors.initials: M
authors.lastname: Johannesson
authors.forename: Lars
authors.initials: L
authors.lastname: Engstrand
authors.forename: Otto
authors.initials: O
authors.lastname: Cars
authors.forename: Dan I
authors.initials: DI
authors.lastname: Andersson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics*; D016983:Enterococcus / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D013210:Staphylococcus / Q000187:drug effects / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents