Improving Antimicrobial Prescribing Practices in the Neonatal ICU

Study Overview
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Brief Summary
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To determine if 3 randomly assigned bundles of stewardship interventions would reduce overall and inappropriate antimicrobial use in the neonatal intensive care unit (NICU), a pre-post study was performed in 4 NICUs.

Detailed Description
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Antimicrobial stewardship can improve the safety and quality of healthcare, reduce antimicrobial resistance, and reduce healthcare costs. However, the optimal strategies for the NICU population are unknown and few studies have evaluated the impact of stewardship in this population. To determine if 3 randomly assigned bundles of stewardship interventions would reduce overall and inappropriate antimicrobial use in the NICU. The investigators hypothesized that the bundle using all three interdisciplinary antimicrobial stewardship strategies (education, computer decision support and prescriber audit and feedback) would more effectively reduce overall and inappropriate antimicrobial use compared to usual care. A pre-post intervention study (one baseline year without interventions - May 1, 2009 - April 30, 2010, followed by two years of interventions - May 1, 2010 - April 30, 2012) was performed in 4 academically affiliated, level III NICUs. The sites were randomly assigned to usual care, one intervention, two interventions, or three interventions.

Official Title
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Improving Antimicrobial Prescribing Practices in the Neonatal Intensive Care Unit

Conditions
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Infants in Neonatal Intensive Care Units

Intervention / Treatment
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* Other: Education Plus (E+)
* Other: Clinical Decision Support
* Other: Prescriber Audit and Feedback


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: infants admitted to study NICUs <7 days of age who remained hospitalized 4 days or more days Exclusion Criteria: Infants admitted to study NICUs 7 days of age and older who were hospitalized less than 4 days
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A pre-post intervention study followed by two years of use of randomly assigned interventions
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: NICU A - E+, CDS, and PAF<br>This site was assigned to three interventions, Education Plus (E+), Clinical Decision Support (CDS), and Prescriber Audit and Feedback (PAB). | Other: Education Plus (E+)<br>* Education Plus was an intervention developed by the study team based on the Center for Disease Control (CDC) 12 Step Campaign to Prevent Antimicrobial Resistance in Healthcare Settings. The study team provided Education Plus quarterly to prescribers at the three sites (NICU A, B, C) randomized to this intervention. Examples of topics presented were an overview of antimicrobial stewardship principles, epidemiology of healthcare-associated infections (HAIs), prevention of surgical site infections, antimicrobial susceptibility testing, and pharmacokinetic principles. Educational formats included didactic lectures, participation via the audience response system, case vignettes, and panel discussions.<br>Other: Clinical Decision Support<br>* The CDS tool was an intervention developed in consultation with neonatologists and pediatric infectious disease physicians from NICU A and B. Algorithms for empiric and targeted antimicrobial therapy for common pathogens and common clinical scenarios using local antimicrobial susceptibility patterns were developed. The CDS tool also provided additional components to facilitate antimicrobial prescribing, e.g., patient weight, day of life, previous culture results, antimicrobial orders, and selected laboratory results including white blood cell and platelet count, C-reactive protein, creatinine, and therapeutic drug levels. NICUs A and B also received E+<br>Other: Prescriber Audit and Feedback<br>* The prescriber audit and feedback (PAF) intervention was developed by the study team which held focus groups with neonatologists at NICU A (the site randomized to this intervention) to determine the feedback parameters and feedback format as previously described. Neonatologists at NICU A were provided aggregated prescribing data bimonthly that described inappropriate use as described below and prolonged therapy (>7 days) for culture-negative late onset sepsis. NICU A also received CDS and E+.<br>|
| Other: NICU B - E+ and CDS<br>This site was assigned to two interventions, Education Plus (E+) and Clinical Decision Support (CDS). | Other: Education Plus (E+)<br>* Education Plus was an intervention developed by the study team based on the Center for Disease Control (CDC) 12 Step Campaign to Prevent Antimicrobial Resistance in Healthcare Settings. The study team provided Education Plus quarterly to prescribers at the three sites (NICU A, B, C) randomized to this intervention. Examples of topics presented were an overview of antimicrobial stewardship principles, epidemiology of healthcare-associated infections (HAIs), prevention of surgical site infections, antimicrobial susceptibility testing, and pharmacokinetic principles. Educational formats included didactic lectures, participation via the audience response system, case vignettes, and panel discussions.<br>Other: Clinical Decision Support<br>* The CDS tool was an intervention developed in consultation with neonatologists and pediatric infectious disease physicians from NICU A and B. Algorithms for empiric and targeted antimicrobial therapy for common pathogens and common clinical scenarios using local antimicrobial susceptibility patterns were developed. The CDS tool also provided additional components to facilitate antimicrobial prescribing, e.g., patient weight, day of life, previous culture results, antimicrobial orders, and selected laboratory results including white blood cell and platelet count, C-reactive protein, creatinine, and therapeutic drug levels. NICUs A and B also received E+<br>|
| Other: NICU C - E+<br>This site was assigned to one intervention, Education Plus (E+). | Other: Education Plus (E+)<br>* Education Plus was an intervention developed by the study team based on the Center for Disease Control (CDC) 12 Step Campaign to Prevent Antimicrobial Resistance in Healthcare Settings. The study team provided Education Plus quarterly to prescribers at the three sites (NICU A, B, C) randomized to this intervention. Examples of topics presented were an overview of antimicrobial stewardship principles, epidemiology of healthcare-associated infections (HAIs), prevention of surgical site infections, antimicrobial susceptibility testing, and pharmacokinetic principles. Educational formats included didactic lectures, participation via the audience response system, case vignettes, and panel discussions.<br>|
| No Intervention: NICU D - Usual Care<br>This site was not introduced to an interdisciplinary intervention. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Antimicrobial Use measured as days of therapy per 100 patient-days | The indications for initiation of intravenous antimicrobials were categorized as initiation of empiric therapy (antibiotics started prior to culture results), definitive therapy (culture results available prior to initiation of antibiotics), or prophylaxis (e.g., antibiotics for postoperative prophylaxis). | Through study completion for 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of therapy per 100 patient-days | 2 agents received on same day counted as one day | Through study completion for 2 years | 
| Inappropriate Antimicrobial Use | Determined on 4th calendar-day of treatment as redundant therapy and failure to target the pathogen | Through study completion for 2 years | 
| Number of infants initiated on ineffective empiric therapy | Initiation of ineffective empiric therapy for infants thought to be infected | Through study completion for 2 years | 
| Proportion of infants treated for culture negative late onset sepsis | The proportion of infants treated for culture negative late onset sepsis lasting more than 7 days | Through study completion for 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neonatal ICU, antimicrobial stewardship