Antimicrobial Stewardship Interventions in a Hospital Setting

A Randomized Antimicrobial Stewardship Trial in a Hospital Setting

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.

Study Overview

• Status: Completed
• Conditions: Infectious Disease
• Intervention / Treatment: Other: Implementation of prospective audit and feedback stewardship interventions to reduce unnecessary use of antimicrobials and improve quality of prescriptions

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 1312
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden
    • Uppsala University Hospital
  • Ystad, Sweden
    • Ystads lasarett

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infectious diseases physician led; 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; Prospective audit and feedback of antimicrobial therapy at hospital wards, by interventions performed by infectious diseases specialists alone or using a team-based approach.
Experimental: Multiprofessional team; 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; Prospective audit and feedback of antimicrobial therapy at hospital wards, by interventions performed by infectious diseases specialists alone or using a team-based approach.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Uppsala University
• Collaborators: Lund University
• Investigators: Principal Investigator: Thomas Tängdén, MD, Phd, Uppsala University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): July 31, 2022
• Study Completion (Actual): July 31, 2022

Study Registration Dates

• First Submitted: June 20, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (Actual): June 28, 2019

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: randomized trial; antimicrobial stewardship; prospective audit and feedback; infectious diseases
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Bacterial Agents; Anti-Infective Agents
• Other Study ID Numbers: Dnr 2018-423

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No