Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

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

Journal of Perinatology volume 42, pages 947–952 (2022)Cite this article

Subjects

Abstract

Objective

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.

Result

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]).

Conclusion

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

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Study Flow Diagram.

Similar content being viewed by others

References

  1. Osowicki J, Gwee A, Noronha J, Britton PN, Isaacs D, Lai TB, et al. Australia-wide point prevalence survey of antimicrobial prescribing in neonatal units: how much and how good? Pediatr Infect Dis J. 2015;34:e185–190.

    Article  Google Scholar 

  2. Patel SJ, Oshodi A, Prasad P, Delamora P, Larson E, Zaoutis T, et al. Antibiotic use in neonatal intensive care units and adherence with Centers for Disease Control and Prevention 12 Step Campaign to Prevent Antimicrobial Resistance. Pediatr Infect Dis J. 2009;28:1047–51.

    Article  Google Scholar 

  3. Pammi M, Hollister E, Neu J. Gut injury and the microbiome in neonates. Clin Perinatol. 2020;47:369–82.

    Article  Google Scholar 

  4. Schwartz DJ, Langdon AE, Dantas G. Understanding the impact of antibiotic perturbation on the human microbiome. Genome Med. 2020;12:82. https://doi.org/10.1186/s13073-020-00782-x.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ting JY, Synnes A, Roberts A, Deshpandey A, Dow K, Yoon E, et al. Association of antibiotic utilization and neonatal outcomes in very-low-birth-weight infants without proven sepsis. JAMA Pediatrics. 2016;170:1181–7.

    Article  Google Scholar 

  6. Ting JY, Synnes A, Roberts A, Deshpandey AC, Dow K, Yang J, et al. Association of antibiotic utilization and neurodevelopmental outcomes among extremely low gestational age neonates without proven sepsis or necrotizing enterocolitis. Am J Perinatol. 2018;35:972–8.

    Article  Google Scholar 

  7. Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev. 2020;10:CD005496.

    PubMed  Google Scholar 

  8. Principi N, Gnocchi M, Gagliardi M, Argentiero A, Neglia C, Esposito S. Prevention of clostridium difficile infection and associated diarrhea: an unsolved problem. Microorganisms. 2020;8:1640.

    Article  CAS  Google Scholar 

  9. King S, Tancredi D, Lenoir-Wijnkoop I, Gould K, Vann H, Connors G, et al. Does probiotic consumption reduce antibiotic utilization for common acute infections? A systematic review and meta-analysis. Eur J Public Health. 2019;29:494–9.

    Article  Google Scholar 

  10. Shah PS, Seidlitz W, Chan P, Yeh S, Musrap N, Lee SK, et al. Internal audit of the Canadian Neonatal Network data collection system. Am J Perinatol. 2017;34:1241–9.

    Article  Google Scholar 

  11. Singh B, Shah PS, Afifi J, Simpson CD, Mitra S, Dow K, et al. Probiotics for preterm infants: a national retrospective cohort study. J Perinatol. 2019;39:533–9.

    Article  Google Scholar 

  12. Health Canada Government of Canada. Licensed Natural Health Products Database (LNHPD). (Accessed 24th May 2021). https://health-products.canada.ca/lnhpd-bdpsnh/index-eng.jsp.

  13. Canadian Neonatal Network. CNN Abstractor’s Mannual. (Accessed May 24, 2021) http://www.canadianneonatalnetwork.org/portal/Portals/0/CNN%20Manual_19Sep2011.pdf.

  14. Richardson DK, Corcoran JD, Escobar GJ, Lee SK. SNAP-II and SNAPPE-II: simplified newborn illness severity and mortality risk scores. J Pediatr. 2001;138:92–100.

    Article  CAS  Google Scholar 

  15. Beltempo M, Shah PS, Ye XY, Afifi J, Lee S, McMillan DD, et al. SNAP-II for prediction of mortality and morbidity in extremely preterm infants. J Matern Fetal Neonatal Med. 2019;32:2694–701.

    Article  Google Scholar 

  16. Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.

    Article  CAS  Google Scholar 

  17. Lui K, Vento M, Modi N, Kusuda S, Lehtonen L, Hakansson S, et al. Inter-center variability in neonatal outcomes of preterm infants: a longitudinal evaluation of 298 neonatal units in 11 countries. Semin Fetal Neonatal Med. 2021;26:101196.

    Article  Google Scholar 

  18. Morgan RL, Preidis GA, Kashyap PC, Weizman AV, Sadeghirad B, McMaster Probiotic P, et al. Probiotics reduce mortality and morbidity in preterm, low-birth-weight infants: a systematic review and network meta-analysis of randomized trials. Gastroenterology. 2020;159:467–80.

    Article  CAS  Google Scholar 

  19. Suez J, Zmora N, Segal E, Elinav E. The pros, cons, and many unknowns of probiotics. Nat Med. 2019;25:716–29.

    Article  CAS  Google Scholar 

  20. Nguyen M, Holdbrooks H, Mishra P, Abrantes MA, Eskew S, Garma M, et al. Impact of probiotic B. infantis EVC001 feeding in premature infants on the gut microbiome, nosocomially acquired antibiotic resistance, and enteric inflammation. Front Pediatr. 2021;9:618009.

    Article  Google Scholar 

  21. Stiemsma LT, Michels KB. The role of the microbiome in the developmental origins of health and disease. Pediatrics. 2018;141:e20172437.

    Article  Google Scholar 

  22. Tamburini S, Shen N, Wu HC, Clemente JC. The microbiome in early life: implications for health outcomes. Nat Med. 2016;22:713–22.

    Article  CAS  Google Scholar 

  23. Russell JT, Lauren Ruoss J, de la Cruz D, Li N, Bazacliu C, Patton L, et al. Antibiotics and the developing intestinal microbiome, metabolome and inflammatory environment in a randomized trial of preterm infants. Sci Rep. 2021;11:1943.

    Article  CAS  Google Scholar 

  24. Alcon-Giner C, Dalby MJ, Caim S, Ketskemety J, Shaw A, Sim K, et al. Microbiota supplementation with bifidobacterium and lactobacillus modifies the preterm infant gut microbiota and metabolome: an observational study. Cell Rep Med. 2020;1:100077.

    Article  Google Scholar 

  25. Barrett E, Kerr C, Murphy K, O’Sullivan O, Ryan CA, Dempsey EM, et al. The individual-specific and diverse nature of the preterm infant microbiota. Arch Dis Child Fetal Neonatal Ed. 2013;98:F334–340.

    Article  Google Scholar 

  26. Baldassarre ME, Di Mauro A, Capozza M, Rizzo V, Schettini F, Panza R, et al. Dysbiosis and prematurity: is there a role for probiotics? Nutrients. 2019;11:1273.

    Article  CAS  Google Scholar 

  27. Henrick BM, Chew S, Casaburi G, Brown HK, Frese SA, Zhou Y, et al. Colonization by B. infantis EVC001 modulates enteric inflammation in exclusively breastfed infants. Pediatr Res. 2019;86:749–57.

    Article  CAS  Google Scholar 

  28. Casaburi G, Duar RM, Vance DP, Mitchell R, Contreras L, Frese SA, et al. Early-life gut microbiome modulation reduces the abundance of antibiotic-resistant bacteria. Antimicrob Resist Infect Control. 2019;8:131.

    Article  Google Scholar 

  29. Underwood MA, Sohn K. The microbiota of the extremely preterm infant. Clin Perinatol. 2017;44:407–27.

    Article  Google Scholar 

  30. Mueller NT, Differding MK, Ostbye T, Hoyo C, Benjamin-Neelon SE. Association of birth mode of delivery with infant faecal microbiota, potential pathobionts, and short chain fatty acids: a longitudinal study over the first year of life. BJOG. 2020;128:1293–303.

    Article  Google Scholar 

  31. Arshad M, Seed PC. Urinary tract infections in the infant. Clin Perinatol. 2015;42:17–28. vii

    Article  Google Scholar 

  32. Pramanik AK, Rangaswamy N, Gates T. Neonatal respiratory distress: a practical approach to its diagnosis and management. Pediatr Clin North Am. 2015;62:453–69.

    Article  Google Scholar 

  33. Beltempo M, Shah P, Yoon E, Chan P, Members of the Annual Report Committee. The Canadian Neonatal Network Annual Report 2019. (Accessed May 20, 2021). http://www.canadianneonatalnetwork.org/portal/Portals/0/Annual%20Reports/2019%20CNN%20report%20final_links.pdf.

  34. Shah P, Yoon E, Chan P, Members of the Annual Report Committee. The Canadian Neonatal Network Annual Report 2016. (Accessed May 20, 2021). http://www.canadianneonatalnetwork.org/portal/Portals/0/Annual%20Reports/2016%20CNN%20report_final_amendment1.pdf.

  35. Schuller SS, Kramer BW, Villamor E, Spittler A, Berger A, Levy O. Immunomodulation to prevent or treat neonatal sepsis: past, present, and future. Front Pediatr. 2018;6:199.

    Article  Google Scholar 

  36. Underwood MA. Arguments for routine administration of probiotics for NEC prevention. Curr Opin Pediatr. 2019;31:188–94.

    Article  Google Scholar 

Download references

Acknowledgements

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.

Funding

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.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Alberta, Edmonton, AB, Canada

    Joseph Y. Ting

  2. Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada

    Joseph Y. Ting

  3. Maternal-infant Care Research Centre, Mount Sinai Hospital, Toronto, ON, Canada

    Eugene W. Yoon & Prakesh S. Shah

  4. Department of Pediatrics, University of Calgary, Calgary, AB, Canada

    Carlos A. Fajardo

  5. Department of Pediatrics, University of Ottawa, Ottawa, ON, Canada

    Thierry Daboval

  6. Department of Pediatrics, Université de Sherbrooke, Sherbrooke, QC, Canada

    Valérie Bertelle

  7. Department of Paediatrics, University of Toronto, Toronto, ON, Canada

    Prakesh S. Shah

  8. Mount Sinai Hospital, Toronto, ON, Canada

    Prakesh S. Shah & Shoo K. Lee

  9. Montreal Children’s Hospital at McGill University Health Centre, Montréal, QC, Canada

    Marc Beltempo & Martine Claveau

  10. Victoria General Hospital, Victoria, BC, Canada

    Jaideep Kanungo

  11. British Columbia Women’s Hospital, Vancouver, BC, Canada

    Jonathan Wong

  12. Royal Columbian Hospital, New Westminster, BC, Canada

    Zenon Cieslak

  13. Surrey Memorial Hospital, Surrey, BC, Canada

    Rebecca Sherlock

  14. Foothills Medical Centre, Calgary, AB, Canada

    Ayman Abou Mehrem

  15. Royal Alexandra Hospital, Edmonton, AB, Canada

    Jennifer Toye & Joseph Y. Ting

  16. Alberta Children’s Hospital, Calgary, AB, Canada

    Carlos Fajardo

  17. Regina General Hospital, Regina, SK, Canada

    Jaya Bodani

  18. Royal University Hospital, Saskatoon, SK, Canada

    Lannae Strueby

  19. Winnipeg Health Sciences Centre, Winnipeg, MB, Canada

    Mary Seshia & Deepak Louis

  20. St. Boniface General Hospital, Winnipeg, MB, Canada

    Ruben Alvaro

  21. Hamilton Health Sciences Centre, Hamilton, ON, Canada

    Amit Mukerji

  22. London Health Sciences Centre, London, ON, Canada

    Orlando Da Silva

  23. Windsor Regional Hospital, Windsor, ON, Canada

    Sajit Augustine

  24. Hospital for Sick Children, Toronto, ON, Canada

    Kyong-Soon Lee

  25. Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Eugene Ng

  26. The Ottawa Hospital, Ottawa, ON, Canada

    Brigitte Lemyre

  27. Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada

    Thierry Daboval

  28. Kingston General Hospital, Kingston, ON, Canada

    Faiza Khurshid

  29. Jewish General Hospital, Montréal, QC, Canada

    Victoria Bizgu

  30. Hôpital Sainte-Justine, Montréal, QC, Canada

    Keith Barrington, Anie Lapointe & Guillaume Ethier

  31. Centre Hospitalier Universitaire de Québec, Sainte Foy, QC, Canada

    Christine Drolet & Bruno Piedboeuf

  32. Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada

    Marie St-Hilaire

  33. Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada

    Valerie Bertelle & Edith Masse

  34. Moncton Hospital, Moncton, New Brunswick, Canada

    Roderick Canning

  35. Everett Chalmers Hospital, Fredericton, NB, Canada

    Hala Makary

  36. Saint John Regional Hospital, Saint John, NB, Canada

    Cecil Ojah & Luis Monterrosa

  37. Janeway Children’s Health and Rehabilitation Centre, St. John’s, NF, Canada

    Julie Emberley

  38. IWK Health Centre, Halifax, NS, Canada

    Jehier Afifi

  39. Cape Breton Regional Hospital, Sydney, NS, Canada

    Andrzej Kajetanowicz

Authors
  1. Joseph Y. Ting
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eugene W. Yoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlos A. Fajardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thierry Daboval
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Valérie Bertelle
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Prakesh S. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Canadian Neonatal Network (CNN) Investigators

  • Prakesh S. Shah
  • , Marc Beltempo
  • , Jaideep Kanungo
  • , Jonathan Wong
  • , Zenon Cieslak
  • , Rebecca Sherlock
  • , Ayman Abou Mehrem
  • , Jennifer Toye
  • , Joseph Y. Ting
  • , Carlos Fajardo
  • , Jaya Bodani
  • , Lannae Strueby
  • , Mary Seshia
  • , Deepak Louis
  • , Ruben Alvaro
  • , Amit Mukerji
  • , Orlando Da Silva
  • , Sajit Augustine
  • , Kyong-Soon Lee
  • , Eugene Ng
  • , Brigitte Lemyre
  • , Thierry Daboval
  • , Faiza Khurshid
  • , Victoria Bizgu
  • , Keith Barrington
  • , Anie Lapointe
  • , Guillaume Ethier
  • , Christine Drolet
  • , Bruno Piedboeuf
  • , Martine Claveau
  • , Marie St-Hilaire
  • , Valerie Bertelle
  • , Edith Masse
  • , Roderick Canning
  • , Hala Makary
  • , Cecil Ojah
  • , Luis Monterrosa
  • , Julie Emberley
  • , Jehier Afifi
  • , Andrzej Kajetanowicz
  •  & Shoo K. Lee

Contributions

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.

Corresponding author

Correspondence to Prakesh S. Shah.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1038/s41372-022-01382-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41372-022-01382-w

Search

Advanced search

Quick links