title: Parallel analysis of individual and aggregated data on antibiotic exposure and resistance in gram-negative bacilli.
abstract: To evaluate the potential bias of analyzing aggregated data, we separately examined antibiotic exposure and resistance data for 35,423 patients admitted to a university hospital in Utah, from both an individual-patient perspective and group-level perspective. From 1994 through 1998, use of defined daily doses (per 1000 patient-days) of fluoroquinolones, third-generation cephalosporins, ampicillin-sulbactam, and imipenem increased by 82%, 38%, and 99%, and decreased by 38%, respectively, whereas group-level resistance rates of Enterobacteriaceae or Pseudomonas species changed only minimally. However, in individual-patient-level analyses performed by multivariable proportional hazards regression, exposure to a fluoroquinolone, third-generation cephalosporin, ampicillin-sulbactam, or imipenem was a strong risk factor for resistance to fluoroquinolones (adjusted hazard ratio [AHR], 4.0; P<.001), third-generation cephalosporins (AHR, 3.5; P<.001), ampicillin-sulbactam (AHR, 2.3; P=.008), or imipenem (AHR, 5.7; P<.001), respectively. Thus, group-level and individual-patient-level analyses of antibiotic-use-versus-susceptibility relations yielded divergent results. Multicenter studies should include individual-patient-level data to elucidate more fully the relation between antibiotic exposure and resistance.
authors.affiliation: Harvard Medical School, Boston, USA. harbarth@post.harvard.edu
authors.forename: S
authors.initials: S
authors.lastname: Harbarth
authors.forename: A D
authors.initials: AD
authors.lastname: Harris
authors.forename: Y
authors.initials: Y
authors.lastname: Carmeli
authors.forename: M H
authors.initials: MH
authors.lastname: Samore
mesh_terms: D000667:Ampicillin / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002511:Cephalosporins / Q000627:therapeutic use*; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011549:Pseudomonas / Q000187:drug effects; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D013223:Statistics as Topic; D013407:Sulbactam / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; C035444:sultamicillin; D015378:Imipenem; D000667:Ampicillin; D013407:Sulbactam