title: Association Between Antibiotic Use and Neonatal Mortality and Morbidities in Very Low-Birth-Weight Infants Without Culture-Proven Sepsis or Necrotizing Enterocolitis.
abstract: Excessive antibiotic use has been associated with altered bacterial colonization and may result in antibiotic resistance, fungemia, necrotizing enterocolitis (NEC), and mortality. Exploring the association between antibiotic exposure and neonatal outcomes other than infection-related morbidities may provide insight on the importance of rational antibiotic use, especially in the setting of culture-negative neonatal sepsis.
  
  
  
  To evaluate the trend of antibiotic use among all hospitalized very low-birth-weight (VLBW) infants across Canada and the association between antibiotic use rates (AURs) and mortality and morbidity among neonates without culture-proven sepsis or NEC.
  
  
  
  A retrospective cohort study was conducted among VLBW infants (<1500 g) admitted to level III neonatal intensive care units between January 1, 2010, and December 31, 2014, using data obtained from the Canadian Neonatal Network database.
  
  
  
  Duration of antibiotic use during the hospitalization period.
  
  
  
  The AUR was defined as the number of days an infant was exposed to 1 or more antimicrobial agents divided by the total length of hospital stay. The composite primary outcome was defined as mortality or major morbidity, including any of the following: persistent periventricular echogenicity or echolucency on neuroimaging, chronic lung disease, and stage 3 or higher retinopathy of prematurity. Multivariable regression analysis was used to calculate adjusted odds ratios (aORs) and 95% CIs for the association between AURs and outcomes.
  
  
  
  Among 13 738 eligible VLBW infants, 11 669 (84.9%) (mean [SD] gestational age, 27.7 [2.5] weeks; 47.4% female) received antibiotics during their hospital course and were included in the study. The annual AUR decreased from 0.29 in 2010 to 0.25 in 2014 (slope for the best-fit line, -0.011; 95% CI, -0.016 to -0.006; P < .01), which occurred in parallel with a reduction in the rate of late-onset sepsis from 19.0% in 2010 to 13.8% in 2014 during the same period. Of the 11 669 infants who were treated with antibiotics of varying duration during their hospital stay, 2845 were diagnosed as having sepsis-related complications. Among the remaining 8824 infants without early-onset sepsis, late-onset sepsis, or NEC, a 10% increase in the AUR was associated with an increased odds of the primary composite outcome (aOR, 1.18; 95% CI, 1.13-1.23), mortality (aOR, 2.04; 95% CI, 1.87-2.21), and stage 3 or higher retinopathy of prematurity (aOR, 1.18; 95% CI, 1.06-1.32).
  
  
  
  Antibiotic use in VLBW infants decreased between 2010 and 2014 in Canada. However, among infants without culture-proven sepsis or without NEC, higher AURs were associated with adverse neonatal outcomes.
authors: Department of Pediatrics, University of British Columbia, Vancouver, Canada.
authors: Joseph Y
authors: JY
authors: Ting
authors: Department of Pediatrics, University of British Columbia, Vancouver, Canada.
authors: Anne
authors: A
authors: Synnes
authors: Department of Pediatrics, University of British Columbia, Vancouver, Canada.
authors: Ashley
authors: A
authors: Roberts
authors: Janeway Children's Health and Rehabilitation Centre, Saint John's, Newfoundland, Canada.
authors: Akhil
authors: A
authors: Deshpandey
authors: Department of Pediatrics, Kingston General Hospital and Queen's University, Kingston, Ontario, Canada.
authors: Kimberly
authors: K
authors: Dow
authors: Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors: Eugene W
authors: EW
authors: Yoon
authors: Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada5Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
authors: Kyong-Soon
authors: KS
authors: Lee
authors: Department of Pediatrics, University of British Columbia, Vancouver, Canada.
authors: Simon
authors: S
authors: Dobson
authors: Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada5Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
authors: Shoo K
authors: SK
authors: Lee
authors: Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada5Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
authors: Prakesh S
authors: PS
authors: Shah
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D002170:Canada; D003422:Critical Care / Q000706:statistics & numerical data; D020345:Enterocolitis, Necrotizing; D005260:Female; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D009017:Morbidity; D018743:Perinatal Care / Q000706:statistics & numerical data; D012189:Retrospective Studies; D018805:Sepsis / Q000401:mortality
chemical_list: D000900:Anti-Bacterial Agents