title: The prevalence of fluoroquinolone resistance mechanisms in colonizing Escherichia coli isolates recovered from hospitalized patients.
abstract: BACKGROUND
  Fluoroquinolones are the most commonly prescribed antimicrobials. The epidemiology of fecal colonization with Escherichia coli demonstrating reduced susceptibility to fluoroquinolones remains unclear.
  
  
  METHODS
  During a 3-year period (15 September 2004 through 19 October 2007), all patients hospitalized for >3 days were approached for fecal sampling. All E. coli isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration [MIC] of levofloxacin, 0.125 microg/mL) were identified. We characterized gyrA and parC mutations and organic solvent tolerance. Isolates were compared using pulsed-field gel electrophoresis.
  
  
  RESULTS
  Of 353 patients colonized with E. coli demonstrating reduced fluoroquinolone susceptibility, 300 (85.0%) had 1 gyrA mutation, 161 (45.6%) had 1 parC mutation, and 171 (48.6%) demonstrated organic solvent tolerance. The mean numbers of total mutations (ie, gyrA and parC) for E. coli isolates with a levofloxacin MIC of 8 microg/mL versus <8.0 microg/mL were 2.70 and 0.82 (P < .001). Of the 136 E. coli isolates with a levofloxacin MIC of 8 microg/mL, 90 (66.2%) demonstrated a nalidixic acid MIC of 16 microg/mL. Significant differences were found over time in the proportion of E. coli isolates demonstrating gyrA mutation, parC mutation, and organic solvent tolerance. There was little evidence of clonal spread of isolates. Conclusions. Gastrointestinal tract colonization with E. coli demonstrating reduced susceptibility to levofloxacin is common. Although 40% of study isolates exhibited a levofloxacin MIC of <8 microg/mL (and would thus be missed by current Clinical and Laboratory Standards Institute breakpoints), nalidixic acid resistance may be a useful marker for detection of such isolates. Significant temporal changes occurred in the proportion of isolates exhibiting various resistance mechanisms.
authors.affiliation: Divisions of Infectious Diseases, University of Pennsylvania School of Medicine, Philadelphia, PA, USA. ebbing@mail.med.upenn.edu
authors.forename: Ebbing
authors.initials: E
authors.lastname: Lautenbach
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Metlay
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Mao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Han
authors.forename: Neil O
authors.initials: NO
authors.lastname: Fishman
authors.forename: Warren B
authors.initials: WB
authors.lastname: Bilker
authors.forename: Pam
authors.initials: P
authors.lastname: Tolomeo
authors.forename: Mary
authors.initials: M
authors.lastname: Wheeler
authors.forename: Irving
authors.initials: I
authors.lastname: Nachamkin
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015373:Bacterial Typing Techniques; D002353:Carrier State / Q000382:microbiology; D016172:DNA Fingerprinting; D027081:DNA Gyrase / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics*; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology*; D006761:Hospitals; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D020125:Mutation, Missense; D015995:Prevalence
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase