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Antimicrobial utilization in very-low-birth-weight infants: association with probiotic use



To examine the association between probiotic use and antimicrobial utilization.

Study design

We retrospectively evaluated very-low-birth-weight (VLBW) infants admitted to tertiary neonatal intensive care units in Canada between 2014 and 2019. Our outcome was antimicrobial utilization rate (AUR) defined as number of days of antimicrobial exposure per 1000 patient-days.


Of 16,223 eligible infants, 7279 (45%) received probiotics. Probiotic use rate increased from 10% in 2014 to 68% in 2019. The AUR was significantly lower in infants who received probiotics vs those who did not (107 vs 129 per 1000 patient-days, aRR = 0.89, 95% CI [0.81, 0.98]). Among 13,305 infants without culture-proven sepsis or necrotizing enterocolitis ≥Stage 2, 5931 (45%) received probiotics. Median AUR was significantly lower in the probiotic vs the no-probiotic group (78 vs 97 per 1000 patient-days, aRR = 0.85, 95% CI [0.74, 0.97]).


Probiotic use was associated with a significant reduction in AUR among VLBW infants.

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Fig. 1: Study Flow Diagram.


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The authors thank all site investigators and data abstractors of the Canadian Neonatal Network (CNN). A list of participating CNN site investigators and their affiliations is presented in the Supplementary Infromation. We thank the staff at the Maternal-infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada, for organizational support of the CNN. In particular, we thank Heather McDonald Kinkaid, PhD, a scientific writer at MiCare, for editorial support in preparing this paper.


Although no specific funding was received for this study, organizational support for the Canadian Neonatal Network was provided by the Maternal-infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by the Canadian Institutes of Health Research (CTP 87518), the Ontario Ministry of Health and Long-Term Care, and Mount Sinai Hospital. Dr JYT receives salary support from the Investigator Grant Award Program of the British Columbia Children’s Hospital Research Institute.

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Authors and Affiliations




JYT conceptualized and designed the study, interpreted the data, drafted the paper, and critically revised the paper for important intellectual content. EWY conducted the statistical analysis, interpreted the data, and critically revised the paper. PSS conceptualized and designed the study, contributed to the statistical analysis and interpreted the data, critically revised the paper for important intellectual content, obtained funding, and provided technical and material support as well as overall study supervision. CAF, TD, and VB interpreted the study data and critically reviewed and revised the paper for important intellectual content. All authors approved the final version of this paper as submitted, and all agree to be accountable for all aspects of the work.

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Correspondence to Prakesh S. Shah.

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Ting, J.Y., Yoon, E.W., Fajardo, C.A. et al. Antimicrobial utilization in very-low-birth-weight infants: association with probiotic use. J Perinatol 42, 947–952 (2022).

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