title: Previous Antibiotic Exposure Increases Risk of Infection with Extended-Spectrum-β-Lactamase- and AmpC-Producing Escherichia coli and Klebsiella pneumoniae in Pediatric Patients.
abstract: The objective of this study was to determine whether antibiotic exposure is associated with extended-spectrum-beta-lactamase- or AmpC-producing Escherichia coli or Klebsiella pneumoniae infections in children. We collected extended-spectrum-beta-lactamase- or AmpC-producing E. coli or K. pneumoniae isolates and same-species susceptible controls from normally sterile sites of patients aged ≤21 years, along with associated clinical data, at four free-standing pediatric centers. After controlling for potential confounders, the relative risk of having an extended-spectrum-beta-lactamase-producing isolate rather than a susceptible isolate was 2.2 times higher (95% confidence interval [CI], 1.49 to 3.35) among those with antibiotic exposure in the 30 days prior to infection than in those with no antibiotic exposure. The results were similar when analyses were limited to exposure to third-generation cephalosporins, other broad-spectrum beta-lactams, or trimethoprim-sulfamethoxazole. Conversely, the relative risk of having an AmpC-producing versus a susceptible isolate was not significantly elevated with any antibiotic exposure in the 30 days prior to infection (adjusted relative risk ratio, 1.12; 95% CI, 0.65 to 1.91). However, when examining subgroups of antibiotics, the relative risk of having an AmpC-producing isolate was higher for patients with exposure to third-generation cephalosporins (adjusted relative risk ratio, 4.48; 95% CI, 1.75 to 11.43). Dose-response relationships between antibiotic exposure and extended-spectrum-beta-lactamase-producing or AmpC-producing isolates were not demonstrated. These results reinforce the need to study and implement pediatric antimicrobial stewardship strategies, and they indicate that epidemiological studies of third-generation cephalosporin-resistant E. coli and K. pneumoniae isolates should include resistance mechanisms when possible.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA Seattle Children's Research Institute, Seattle, Washington, USA danielle.zerr@seattlechildrens.org.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Zerr
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, Washington, USA.
authors.forename: Arianna
authors.initials: A
authors.lastname: Miles-Jay
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Kronman
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Adler
authors.affiliation: Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Wren
authors.initials: W
authors.lastname: Haaland
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington, USA Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Weissman
authors.affiliation: Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA St. Louis Children's Hospital, St. Louis, Missouri, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Elward
authors.affiliation: Department of Pediatrics, University of Missouri-Kansas City, Kansas City, Missouri, USA Children's Mercy Hospital and Clinics, Kansas City, Missouri, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Newland
authors.affiliation: Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Theoklis
authors.initials: T
authors.lastname: Zaoutis
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA Seattle Children's Research Institute, Seattle, Washington, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Qin
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001398:Aztreonam / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics; D000077723:Cefepime; D002439:Cefotaxime / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology; D002648:Child; D002675:Child, Preschool; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology* / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000201:enzymology / Q000235:genetics; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007710:Klebsiella Infections / Q000201:enzymology / Q000235:genetics; D007711:Klebsiella pneumoniae / Q000201:enzymology* / Q000472:pathogenicity*; D008297:Male; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D055815:Young Adult; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D002443:Ceftriaxone; D000077723:Cefepime; D002442:Ceftazidime; D001618:beta-Lactamases; D001398:Aztreonam; D002439:Cefotaxime