Antimicrobial Stewardship Interventions in a Hospital Setting

Study Overview
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Brief Summary
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The emerging crisis of multidrug-resistant bacteria is accelerated by a massive overuse and misuse of antibiotics. It has been estimated that 50% of antibiotic prescriptions are inappropriate. Antibiotic interventions to improve prescribing patterns have been successfully implemented in primary care in Sweden and other countries. However, much of the last-resort antibiotics are used in hospitals in which decisions on therapy for bacterial infections are more complex. In this project we will explore the appropriateness of antibiotic prescribing in a hospital setting and measures to improve the quality of antimicrobial therapy. Antimicrobial stewardship interventions will be conducted at selected hospital departments using prospective audit and feedback in a multifaceted and cross-disciplinary approach. The intervention effects on antibiotic consumption, appropriateness of prescriptions, patient outcome and emergence of resistance will be evaluated, and a financial cost-effectiveness analysis will be performed.

Detailed Description
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Background: In this project we will address the issue of inappropriate antibiotic prescribing in a hospital setting using a systematic and cross-disciplinary approach. We believe that a substantial reduction in antibiotic use and a significant improvement in prescribing patterns can be achieved, which will benefit the patients by reducing the risks of side effects such as antibiotic-induced Clostridium difficile enteritis. Aim: The aim of this study is to implement and evaluate antibiotic interventions at targeted hospital wards. Method: Hospital wards will be randomised to one of two antimicrobial stewardship intervention arms stratified by specialty (medicine or surgery). Prospective audit and feedback is a core intervention strategy in both arms. Statistics: Interrupted time-series analysis (ITS) will be used for the primary endpoint; volume of antimicrobial prescribing. Monthly baseline data at least five years prior to start of the intervention and a during a follow-up period of at least 12 months after end of the intervention period will be used to assess immediate and sustained effects. Endpoints and outcomes: Primary endpoint is reduction in antibiotic use, days of antibiotic therapy (DOTs)/100 patient days Secondary endpoints include outcome measures for quantity of antibiotic use, appropriateness of prescriptions, clinical and microbiological outcome and cost-effectiveness. Data on antibiotic use and trends in prescriptions of key antibiotics will be obtained from hospital pharmacies. Data on duration of hospitalization, patient mortality, re-admissions and side effects including antibiotic-associated Clostridium difficile enteritis will be extracted from the medical records to assess potential impact on patient outcome caused by the intervention. Data on emergence of resistance during therapy and general trends in resistance epidemiology will be recorded. The outcome assessment will include a survey to participating physicians on the value different aspects of the stewardship intervention in their daily care of patients with infections. A cost-effectiveness analysis of the intervention will be performed.

Official Title
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A Randomized Antimicrobial Stewardship Trial in a Hospital Setting

Conditions
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Infectious Disease

Intervention / Treatment
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* Other: Implementation of prospective audit and feedback stewardship interventions to reduce unnecessary use of antimicrobials and improve quality of prescriptions


Participation Criteria
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Eligibility Criteria
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Randomization to intervention arms is performed on ward level. Eligibility criteria: - Surgical or medical wards Patient level (too be included in the outcome analyses) Inclusion Criteria: At least 18 years of age Ongoing antimicrobial therapy on a study ward Signed informed consent Exclusion Criteria: Patients in palliative care with very short life expectancy Patients from another county than study site

Ages Eligible for Study
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Minimum Age: 18 Years

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infectious diseases physician led<br>Prospective audit and feedback of antimicrobial therapy by infectious disease physicians twice weekly Also including standard of care infectious disease consultant on demand hospital antimicrobial stewardship program as usual (education, general information, feedback on prescribing) | Other: Implementation of prospective audit and feedback stewardship interventions to reduce unnecessary use of antimicrobials and improve quality of prescriptions<br>* Prospective audit and feedback of antimicrobial therapy at hospital wards, by interventions performed by infectious diseases specialists alone or using a team-based approach.<br>|
| Experimental: Multiprofessional team<br>Prospective audit and feedback of antimicrobial therapy by infectious disease physicians once weekly, ward clinical pharmacists thrice weekly and engagement of ward nurses in the stewardship intervention Also including standard of care infectious disease consultant on demand hospital antimicrobial stewardship program as usual (education, general information, feedback on prescribing) | Other: Implementation of prospective audit and feedback stewardship interventions to reduce unnecessary use of antimicrobials and improve quality of prescriptions<br>* Prospective audit and feedback of antimicrobial therapy at hospital wards, by interventions performed by infectious diseases specialists alone or using a team-based approach.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change and trends in days of antibiotic therapy (DOT)/100 patient days | Monthly DOT of antibiotics per 100 patient days on ward level assessed 5 y pre-intervention and 1 y post-intervention. Data will be analysed using interrupted time series analysis to assess immediate changes following implementation and comparison of trends before and after the intervention. | 7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days of defined daily doses (DDDs)/100 patient days | Overall days of therapy per 100 patient days (PD) on the ward level | 12 months | 
| Treatment duration (Days per treatment period overall) | Overall days per treatment episode. A treatment episode is defined as antimicrobial treatment not interrupted by more than one calendar day. | 12 months | 
| 30-d mortality | All cause 30-d mortality | 12 months | 
| In-hospital mortality | All-cause in-hospital mortality | 12 months | 
| Hospital readmission within 30 d after discharge | Unplanned hospital readmission within 30 d after discharge | 12 months | 
| Hospital readmission due to relapse of infection within 30 d after discharge | Unplanned hospital readmission due to relapse of infection within 30 d after discharge | 12 months | 
| Hospital length of stay (LOS) | Hospital length of stay per admission | 12 months | 
| Intensive Care Unit (ICU) transfer | Proportion of admissions transferred to ICU after initial non-ICU admission | 12 months | 
| Guideline compliance | Proportion of patients treated where antimicrobial therapy was in compliance with local guideline, or in absence of local guideline national guideline | 12 months | 
| De-escalation or shift to targeted therapy | Proportion of patients where de-escalation or shift to targeted antibiotic therapy occurred within 72 hours after initiation of treatment | 12 months | 
| Intravenous to oral switch | Proportion of patients where intravenous antibiotics was shifted to oral therapy within 5 days (if appropriate) | 12 months | 
| Appropriate diagnostic examinations | Proportion of patients with appropriate diagnostic examinations performed, according to local guidelines, or in the absence of local guidelines national guidelines | 12 months | 
| Dose adjustment for renal function within 48 h after initiation of antimicrobial therapy at admission | Dose adjustment of antimicrobial after the most critical phase of the infection | 12 months | 
| Dose adjustment for renal function when initiating antimicrobial therapy in a non-acute situation | Proportion of antimicrobial prescription in non-acute situations where dosing was according to renal function | 12 months | 
| Therapeutic drug monitoring (TDM) | Proportion of patients where TDM was used, when applicable according to local guideline | 12 months | 
| Drug-drug interactions (DDI) | Important DDI taken into account when prescribing antimicrobial therapy | 12 months | 
| Incidence of Clostridium difficile infections (CDI) | Incidence of healthcare-facility onset CDI denominated by 10 000 PD and admission | 12 months | 
| Incidence of multidrug-resistant organisms (MDRO) | Incidence of clinical cultures with multidrug resistant organisms (methicillin-resistant Staphylococcus aureus (MRSA), Extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E), carbapenemase-producing Enterobacteriaceae (CPE), vancomycin-resistant enterococci (VRE), multidrug resistant P. aeruginosa) denominated per 1000 PD and admissions | 12 months | 
| Costs of administered antimicrobials | Costs of administered antimicrobials (overall and by class) per admission and per patient receiving antibiotics | 12 months | 
| Costs of the intervention | Total costs of the intervention | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antimicrobial stewardship, prospective audit and feedback, infectious diseases, randomized trial