Antimicrobial utilisation patterns between 2013 and 2022 in Canadian neonates born at less than 33 weeks gestation: a retrospective cohort study

Background: Excessive antimicrobial exposure is associated with an increase in neonatal mortality, morbidities and adverse neurodevelopment. Canadian Neonatal Network has been promoting judicious antimicrobial use through the Evidence-based Practice for Improving Quality processes. Our objective was to evaluate the antimicrobial consumption among neonates in tertiary neonatal intensive care units (NICU) in Canada in the recent decade. Methods: This is a retrospective cohort study including data from very preterm infants (born at <33 weeks gestational age) admitted to all NICUs in Canada between January 1, 2013, and December 31, 2022. Nationwide antimicrobial utilization rate (AUR) benchmarking started in 2016, and quality improvement initiatives were continued in the subsequent years to promote judicious use of antimicrobials across the network. AUR is defined as the number of days with ≥1 antimicrobial divided by the total patient days (PD). Culture-proven sepsis refers to a neonate with positive culture of pathogens in blood and/or cerebrospinal fluid. The outcomes were evaluated during pre- (2013-2017) and post-intervention periods (2018-2022). Interrupted time-series analysis was used, and comparison of AUR calculated per each 3-month time block and the slope changes were conducted across the pre- and post-intervention periods regarding total patients and subgroups. Findings: A total of 41,253 infants were included, with 22,644 (55%) being male. The AUR was significantly lower among infants from the post- vs. those from the pre-intervention periods (152 vs. 184, p < 0.0001). Among 35,670 infants without culture-proven sepsis or necrotizing enterocolitis ≥ Stage 2, AUR was significantly lower in the post-intervention group vs. the pre-intervention group (110 vs. 136, p < 0.0001). Interrupted time-series showed significant reduction in AUR during both pre- and post-intervention periods among all infants with and without culture proven sepsis or necrotizing enterocolitis ≥ Stage 2 (all p < 0.0001), as well as those born at <29 weeks gestational age. Interpretation: A comprehensive, network-wide quality improvement initiatives led to a significant and sustained reduction in antimicrobial use among preterm infants born at <33 weeks gestational age with and without culture-proven sepsis or necrotizing enterocolitis ≥ Stage 2. Funding: This study was supported by the Canadian Institutes of Health Research Project Grant 2019 (201903PJT-420294-CA2-CAAA-245530), matched funding from the British Columbia Women's Health Foundation and start-up funding from the Women and Children's Health Research Institute, University of Alberta. The coordinating center in Toronto is funded by the Canadian Institutes of Health Research grant for the Canadian Preterm Birth Network (PBN 150642).