Antimicrobial Stewardship Interventions in a Hospital Setting

Infectious Disease Clinical Trial

Official title:

A Randomized Antimicrobial Stewardship Trial in a Hospital Setting

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04001309
• Other study ID #: Dnr 2018-423
• Status: Completed
• Phase: N/A
• Start date: July 1, 2019
• Est. completion date: July 31, 2022

Study information

• Verified date: December 2022
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1312
• Est. completion date: July 31, 2022
• Est. primary completion date: July 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Infectious Disease

Intervention

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.

Locations

Country	Name	City	State
Sweden	Uppsala University Hospital	Uppsala
Sweden	Ystads lasarett	Ystad

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	Lund University

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Days of defined daily doses (DDDs)/100 patient days	Overall days of therapy per 100 patient days (PD) on the ward level	12 months
Secondary	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
Secondary	30-d mortality	All cause 30-d mortality	12 months
Secondary	In-hospital mortality	All-cause in-hospital mortality	12 months
Secondary	Hospital readmission within 30 d after discharge	Unplanned hospital readmission within 30 d after discharge	12 months
Secondary	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
Secondary	Hospital length of stay (LOS)	Hospital length of stay per admission	12 months
Secondary	Intensive Care Unit (ICU) transfer	Proportion of admissions transferred to ICU after initial non-ICU admission	12 months
Secondary	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
Secondary	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
Secondary	Intravenous to oral switch	Proportion of patients where intravenous antibiotics was shifted to oral therapy within 5 days (if appropriate)	12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Therapeutic drug monitoring (TDM)	Proportion of patients where TDM was used, when applicable according to local guideline	12 months
Secondary	Drug-drug interactions (DDI)	Important DDI taken into account when prescribing antimicrobial therapy	12 months
Secondary	Incidence of Clostridium difficile infections (CDI)	Incidence of healthcare-facility onset CDI denominated by 10 000 PD and admission	12 months
Secondary	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
Secondary	Costs of administered antimicrobials	Costs of administered antimicrobials (overall and by class) per admission and per patient receiving antibiotics	12 months
Secondary	Costs of the intervention	Total costs of the intervention	12 months