title: Previous antimicrobial exposure is associated with drug-resistant urinary tract infections in children.
abstract: OBJECTIVE
  The aim of this study was to evaluate the impact of previous antimicrobial exposure on the development of antimicrobial resistance in children with their first urinary tract infection (UTI).
  
  
  METHODS
  We conducted a retrospective cohort study of children aged 6 months to 6 years and received their first diagnosis of UTI in a network of 27 outpatient pediatric practices between July 1, 2001, and May 31, 2006. We examined the relationship between antimicrobial resistance in UTI isolates and exposure to specific antimicrobial agents (amoxicillin, amoxicillin-clavulanate, cefdinir, trimethoprim-sulfamethoxazole, and azithromycin) in the previous 120 days. We developed multivariable logistic regression models for resistance to ampicillin, amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, and first-generation and third-generation cephalosporins, adjusting for potential confounders such as age, number of siblings, recent hospitalizations, and child care exposure.
  
  
  RESULTS
  Of the 533 children who had a first UTI, 8%, 14%, and 21% were exposed to antimicrobial agents within 30, 60, and 120 days before the UTI, respectively. Amoxicillin exposure within 30 days (odds ratio [OR]: 3.6 [95% confidence interval (CI): 1.6-8.2]) and 31 to 60 days (OR: 2.8 [95% CI: 1.0-7.5]) before UTI both were associated with ampicillin resistance. Exposure to amoxicillin >60 days before the UTI was not associated with ampicillin resistance. Amoxicillin exposure within 30 days of UTI was also associated with amoxicillin-clavulanate resistance (OR: 3.9 [95% CI: 1.8-8.7]). No association between exposure to other antimicrobial agents and resistance to any of the antimicrobial agents was seen.
  
  
  CONCLUSIONS
  Recent antimicrobial exposure is associated with antimicrobial-resistant UTIs among pediatric outpatients, and the magnitude of this association decreases with time since exposure. Judicious antimicrobial prescribers should consider this association when selecting empiric antimicrobial agents for a new UTI and should use strategies to reduce unnecessary antimicrobial use to avoid development of resistant bacteria.
authors.affiliation: Children's Hospital of Philadelphia, Division of Infectious Diseases, 3615 Civic Center Blvd, ARC 1202, Philadelphia, PA 19104, USA. paschke@email.chop.edu
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Paschke
authors.forename: Theoklis
authors.initials: T
authors.lastname: Zaoutis
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Conway
authors.forename: Dawei
authors.initials: D
authors.lastname: Xie
authors.forename: Ron
authors.initials: R
authors.lastname: Keren
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D012189:Retrospective Studies; D013997:Time Factors; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000453:epidemiology* / Q000382:microbiology
chemical_list: D000890:Anti-Infective Agents