Development of a national neonatal intensive care unit-specific antimicrobial stewardship programme in Canada: protocol for a cohort study

Joseph Y Ting, Ashley Roberts, Peter Tilley, Joan L Robinson, Michael S Dunn, Vanessa Paquette, Kyong-Soon Lee, Vibhuti Shah, Eugene Yoon, Lindsay L Richter, Abhay Lodha, Sandesh Shivananda, Nisha Thampi, Julie Autmizguine, Prakesh S Shah, Canadian Neonatal Network Investigators, Joseph Y Ting, Ashley Roberts, Peter Tilley, Joan L Robinson, Michael S Dunn, Vanessa Paquette, Kyong-Soon Lee, Vibhuti Shah, Eugene Yoon, Lindsay L Richter, Abhay Lodha, Sandesh Shivananda, Nisha Thampi, Julie Autmizguine, Prakesh S Shah, Canadian Neonatal Network Investigators

Abstract

Introduction: Early empiric treatment with broad-spectrum antimicrobials is common in neonatal intensive care units (NICU) due to the non-specific clinical presentation of infection. However, excessive and inappropriate antimicrobial use can lead to the emergence of drug-resistant organisms and adverse neonatal outcomes. This study aims to develop and implement a nationwide NICU-specific antimicrobial stewardship programme (ASP) to promote judicious antimicrobial use and control the emergence of multidrug-resistant organisms (MDROs) in Canada.

Methods and analysis: Our study population will include all very low-birth-weight neonates admitted to participating tertiary NICU in Canada. Based on the existing limited literature, we will develop consensus on NICU antimicrobial stewardship interventions to enhance best practices. Using an expanded Canadian Neonatal Network (CNN) platform, we will collect data on antimicrobial use and the susceptibility of organisms identified in clinical samples from blood and cerebrospinal fluid over a period of 2 years. These data will be used to provide all NICU stakeholders with benchmarked centre-adjusted antimicrobial use and MDRO prevalence reports. An ASP plan will be developed at both individual unit and national levels in the subsequent years. Knowledge translation strategies will be implemented through the well-established Evidence-based Practice for Improving Quality methodology.

Ethics and dissemination: Ethics for the study has been granted by the University of British Columbia Children's & Women's Research Ethics Board (H19-02490) and supported by CNN Executive Committee. The study results will be disseminated through national organisations and open access peer-reviewed publications.

Trial registration number: NCT04388293.

Keywords: infectious diseases; neonatal intensive & critical care; neonatology.

Conflict of interest statement

Competing interests: JT is supported by the Investigator Grant Award Program through the British Columbia Children’s Hospital Research Institute. Dr Prakesh S Shah reported holding an Applied Research Chair in Reproductive and Child Health Services and Policy Research awarded by the Canadian Institutes of Health Research (grant APR-126340).

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Approximate timeline of national neonatal intensive care unit-specific ASP plan. ASP, antimicrobial stewardship programme; iKT, integrated knowledge translation; MDRO, multidrug-resistant organism.

References

    1. Hornik CP, Fort P, Clark RH, et al. . Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev 2012;88 Suppl 2:S69–74. 10.1016/S0378-3782(12)70019-1
    1. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am 2013;60:367–89. 10.1016/j.pcl.2012.12.003
    1. Mukhopadhyay S, Puopolo KM. Antibiotic use and mortality among premature infants without confirmed Infection-Perpetrator or innocent bystander? JAMA Pediatr 2016;170:1144–6. 10.1001/jamapediatrics.2016.2836
    1. Cantey JB, Patel SJ. Antimicrobial stewardship in the NICU. Infect Dis Clin North Am 2014;28:247–61. 10.1016/j.idc.2014.01.005
    1. Patel SJ, Oshodi A, Prasad P, 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. 10.1097/INF.0b013e3181b12484
    1. Ting JY, Roberts A, Sherlock R, et al. . Duration of initial empirical antibiotic therapy and outcomes in very low birth weight infants. Pediatrics 2019;143:e20182286. 10.1542/peds.2018-2286
    1. Ting JY, Synnes A, Roberts A, et al. . Association of antibiotic utilization and neonatal outcomes in very-low-birth-weight infants without proven sepsis. JAMA Pediatrics 2016;170:1181–7.
    1. Ting JY, Synnes A, Roberts A, 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. 10.1055/s-0038-1632390
    1. Cotten CM. Adverse consequences of neonatal antibiotic exposure. Curr Opin Pediatr 2016;28:141–9. 10.1097/MOP.0000000000000338
    1. Cotten CM, McDonald S, Stoll B, et al. . The association of third-generation cephalosporin use and invasive candidiasis in extremely low birth-weight infants. Pediatrics 2006;118:717–22. 10.1542/peds.2005-2677
    1. Neu J, Douglas-Escobar M, Lopez M. Microbes and the developing gastrointestinal tract. Nutr Clin Pract 2007;22:174–82. 10.1177/0115426507022002174
    1. Kuppala VS, Meinzen-Derr J, Morrow AL, et al. . Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants. J Pediatr 2011;159:720–5. 10.1016/j.jpeds.2011.05.033
    1. Dellit TH, Owens RC, McGowan JE, et al. . Infectious diseases Society of America and the Society for healthcare epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007;44:159–77. 10.1086/510393
    1. Patel SJ, Saiman L. Antibiotic resistance in neonatal intensive care unit pathogens: mechanisms, clinical impact, and prevention including antibiotic stewardship. Clin Perinatol 2010;37:547–63. 10.1016/j.clp.2010.06.004
    1. Ting J, Roberts A, Yoon E, et al. . ePAS2019:2826.208 Variability and trends in antimicrobial utilization rates among infants born at <33 weeks’ gestational age. Pediatric Academic Societies Meeting. USA: Baltimore MD, 2019.
    1. Ting JY, Paquette V, Ng K, et al. . Reduction of inappropriate antimicrobial prescriptions in a tertiary neonatal intensive care unit after antimicrobial stewardship care bundle implementation. Pediatr Infect Dis J 2019;38:54–9. 10.1097/INF.0000000000002039
    1. Centres for Disease Control and Prevention Cdc 12-step program to prevent antimicrobial resistance in health care settings. Available: [Accessed 19 Apr 2002].
    1. Johnson CL, Saiman L. A blueprint for targeted antimicrobial stewardship in neonatal intensive care units. Infect Control Hosp Epidemiol 2017;38:1144–6. 10.1017/ice.2017.183
    1. Ting JY, Shah PS. Antibiotic stewardship in neonates: challenges and opportunities. Transl Pediatr 2020;9:198–201. 10.21037/tp-20-134
    1. Araujo da Silva AR, Marques A, Di Biase C, et al. . Effectiveness of antimicrobial stewardship programmes in neonatology: a systematic review. Arch Dis Child 2020;105:563–8. 10.1136/archdischild-2019-318026
    1. Douglas-Escobar M, Elliott E, Neu J. Effect of intestinal microbial ecology on the developing brain. JAMA Pediatr 2013;167:374–9. 10.1001/jamapediatrics.2013.497
    1. Shah PS, Chan P, Yoon EY. Canadian Neonatal Network - Major anomalies list, 2013: 124–7.
    1. Shah P, Yoon E, Chan P, et al. . The Canadian neonatal network annual report, 2014. Available:
    1. Shah P, Yoon E, Chan P, et al. . The Canadian neonatal network annual report, 2015. Available:
    1. Shah P, Yoon E, Chan P, et al. . The Canadian neonatal network annual report, 2016. Available:
    1. Shah P, Yoon E, Chan P, et al. . The Canadian neonatal network annual report, 2017. Available:
    1. Shirai Y, Arai H, Tamaki K, et al. . Neonatal methicillin-resistant Staphylococcus aureus colonization and infection. J Neonatal Perinatal Med 2017;10:439–44. 10.3233/NPM-16166
    1. Huang Y-C, Chou Y-H, Su L-H, et al. . Methicillin-Resistant Staphylococcus aureus colonization and its association with infection among infants hospitalized in neonatal intensive care units. Pediatrics 2006;118:469–74. 10.1542/peds.2006-0254
    1. Kent A, Kortsalioudaki C, Monahan IM, et al. . Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study. Arch Dis Child Fetal Neonatal Ed 2016;101:F507–12. 10.1136/archdischild-2015-309554
    1. Tsai M-H, Chu S-M, Hsu J-F, et al. . Risk factors and outcomes for multidrug-resistant gram-negative bacteremia in the NICU. Pediatrics 2014;133:e322–9. 10.1542/peds.2013-1248
    1. Chiu C-H, Michelow IC, Cronin J, et al. . Effectiveness of a guideline to reduce vancomycin use in the neonatal intensive care unit. Pediatr Infect Dis J 2011;30:273–8. 10.1097/INF.0b013e3182011d12
    1. Calil R, Marba ST, von Nowakonski A, et al. . Reduction in colonization and nosocomial infection by multiresistant bacteria in a neonatal unit after institution of educational measures and restriction in the use of cephalosporins. Am J Infect Control 2001;29:133–8. 10.1067/mic.2001.114223
    1. Kitson AL, Rycroft-Malone J, Harvey G, et al. . Evaluating the successful implementation of evidence into practice using the PARiHS framework: theoretical and practical challenges. Implement Sci 2008;3:1. 10.1186/1748-5908-3-1
    1. Kitson A, Harvey G, McCormack B. Enabling the implementation of evidence based practice: a conceptual framework. Qual Health Care 1998;7:149–58. 10.1136/qshc.7.3.149
    1. Roberts A. Using Antimicrobials Judiciously in an Age of Drug Resistance: Teaching Principles of Antimicrobial Stewardship to the next generation of Health Care Providers [program. Vancouver BC, Canada.: UBC Teaching and Learning Enhancement Fund: 2015–7.
    1. Canadian neonatal network Abstracors' manual, 2015. Available:
    1. Lee SK, Shah PS, Singhal N, et al. . Association of a quality improvement program with neonatal outcomes in extremely preterm infants: a prospective cohort study. CMAJ 2014;186:E485–94. 10.1503/cmaj.140399

Source: PubMed

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