Antimicrobial Stewardship for Enterobacterales Bacteremia Management

A Cluster-randomized Controlled Pragmatic Trial to Evaluate Antimicrobial Stewardship Strategies for Short-course and Oral-switch Antibiotic Therapy for Bloodstream Infections Due to Enterobacterales

We hypothesize that a multifaceted antibiotic stewardship intervention incorporating physician education, prospective chart review with antibiotic recommendation, and provision of follow-up by a multidisciplinary antibiotic stewardship team, is more effective than physician education and reminders alone in improving physicians' prescription of short-course and oral-switch antibiotic therapy for patients with bloodstream infections due to Enterobacterales (BSI-E).

This study is to:

1. determine the effectiveness of a multifaceted antibiotic stewardship intervention in improving physicians' prescription of short-course antibiotic therapy for BSI-E
2. determine the effectiveness of a multifaceted antibiotic stewardship intervention in improving physicians' de-escalation to oral antibiotic therapy for BSI-E

Study Overview

• Status: Not yet recruiting
• Conditions: Infections
• Intervention / Treatment: Behavioral: multifaceted antibiotic stewardship intervention

Detailed Description

Antimicrobial resistance is a major global threat, causing 5 million deaths globally in 2019. One of the crucial strategies to control the emergence and spread of multidrug-resistant organisms (MDRO) is to minimize unnecessary antibiotics exposure.

Shorter duration of antibiotic therapy and oral-switch therapy for bloodstream infection due to Enterobacterales (BSI-E) had demonstrated similar treatment success and clinical outcomes as compared with longer courses in randomized controlled trials. Despite the release of such data, clinicians may be reluctant to shortern duration of therapy for BSI-E and adopt oral-switch approach.

This study aims to determine the optimal approach to aid clinicians in adopting evidence-based practice in a clinical setting. This study is a pragmatic cluster-randomized controlled trial in the medical wards of an acute hospital. A cluster, as the unit of randomization, is a medical ward. Medical wards will be randomized to three groups: (1) physician education only; (2) physician education and paper reminder; (3) multifaceted antibiotic stewardship intervention. The prescription of antibiotic therapy by treating physicians and outcomes of patients with BSI-E will be studied.

Patients' antibiotics regimen and clinical outcomes in the three groups will be compared.

• Study Type: Interventional
• Enrollment (Estimated): 420
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Catherine Cheung; Phone Number: 35053376; Email: catherinecheung@cuhk.edu.hk

Study Locations

• Hong Kong
  • Sha Tin, Hong Kong
    • Prince Of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• aged ≥18 years;
• hospitalization in one of the medical wards of the hospital; and
• isolation of Enterobacterales in at least one blood culture bottle, where Enterobacterales include Escherichia coli, Klebsiella, Proteus, Enterobacter, Serratia, Citrobacter, Providencia and Morganella species.

Exclusion Criteria:

• concomitant isolation of pathogens other than Enterobacterales in blood or other relevant clinical specimens;
• infections requiring prolonged courses of antibiotics, such as intra-abdominal abscess, central nervous system infection, endocarditis, lung abscess or empyema, osteomyelitis, and prostatitis;
• focus of infection not controlled;
• nosocomial infection with onset within 7 days; or
• Presence of neutropenia, allogenic stem cell transplant within one year, use of high-dose steroid (>40mg prednisolone or equivalent for > 2 weeks), or
• died before day 7 will be excluded from the analysis, or
• already on more than 7 days of antibiotics for BSI-E at the time of screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group 1 wards (physician education); For Group 1 wards, physician education will be provided. All physicians treating patients in general medical wards will undergo a training session at the start of the study. Education content includes latest evidence on short-course antibiotic therapy and criteria for de-escalation to oral antibiotics for BSI-E. The educational materials will be prepared by Infectious Diseases physicians, and will be presented during one of the monthly departmental meetings, which routinely involve physician education. Ample time will be provided for answering questions from physicians. During the study period, the same material will be presented to new medical staff joining the department. The educational materials will be sent to all physicians in the department regardless of their attendance of the meeting. Patients will receive standard of care.	Behavioral: multifaceted antibiotic stewardship intervention; Group 3 wards will receive a multifaceted antibiotic stewardship intervention. Physician education will be provided as in Group 1. All consecutive patients fulfilling inclusion and exclusion criteria for study eligibility will be assessed by an Antibiotic Stewardship team. A trained nurse will first assess the patients for clinical and host criteria to determine eligibility for short-course antibiotic therapy. The antibiotic susceptibility test results and the prescribed antibiotics treatment will be reviewed. An Infectious Diseases physician will subsequently make written recommendations for the duration and choice of antibiotic therapy, and provide an appointment within 2 weeks after hospital discharge to review patients' clinical condition when indicated.
Active Comparator: Group 2 wards (physician education + paper reminder); For Group 2 wards, physician education will be provided as in Group 1. A paper reminder will be attached in the medical records of all consecutive patients on the first working day after Enterobacterale is isolated from blood culture. The reminder documents (1) the clinical and host criteria that should be considered for prescribing short-course antibiotic therapy, and (2) options of oral antibiotics to complete the treatment course. These recommendations are based on results of the trials demonstrating non-inferiority of short-course and oral-switch therapy for BSI-E.	Behavioral: multifaceted antibiotic stewardship intervention; Group 3 wards will receive a multifaceted antibiotic stewardship intervention. Physician education will be provided as in Group 1. All consecutive patients fulfilling inclusion and exclusion criteria for study eligibility will be assessed by an Antibiotic Stewardship team. A trained nurse will first assess the patients for clinical and host criteria to determine eligibility for short-course antibiotic therapy. The antibiotic susceptibility test results and the prescribed antibiotics treatment will be reviewed. An Infectious Diseases physician will subsequently make written recommendations for the duration and choice of antibiotic therapy, and provide an appointment within 2 weeks after hospital discharge to review patients' clinical condition when indicated.
Active Comparator: Group 3 wards (multifaceted antibiotic stewardship intervention); Group 3 wards will receive a multifaceted antibiotic stewardship intervention. Physician education will be provided as in Group 1. All consecutive patients fulfilling inclusion and exclusion criteria for study eligibility will be assessed by an Antibiotic Stewardship team. A trained nurse will first assess the patients for clinical and host criteria to determine eligibility for short-course antibiotic therapy. The antibiotic susceptibility test results and the prescribed antibiotics treatment will be reviewed. An Infectious Diseases physician will subsequently make written recommendations for the duration and choice of antibiotic therapy, and provide an appointment within 2 weeks after hospital discharge to review patients' clinical condition when indicated.	Behavioral: multifaceted antibiotic stewardship intervention; Group 3 wards will receive a multifaceted antibiotic stewardship intervention. Physician education will be provided as in Group 1. All consecutive patients fulfilling inclusion and exclusion criteria for study eligibility will be assessed by an Antibiotic Stewardship team. A trained nurse will first assess the patients for clinical and host criteria to determine eligibility for short-course antibiotic therapy. The antibiotic susceptibility test results and the prescribed antibiotics treatment will be reviewed. An Infectious Diseases physician will subsequently make written recommendations for the duration and choice of antibiotic therapy, and provide an appointment within 2 weeks after hospital discharge to review patients' clinical condition when indicated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients receiving 7 days effective antibiotic therapy for the treatment of BSI-E	proportion of patients receiving 7 days of effective antibiotic therapy for the treatment of BSI-E	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
proportion of patients with susceptible oral antibiotics completed the course with an oral antibiotic	proportion of patients with susceptible oral antibiotics completed the course with an oral antibiotic	during hopsitalization
30-day all-cause mortality	30-day all-cause mortality	30 day since hospital admission
clinical failure	clinical failure , defined as relapse of BSI-E due to the same Enterobacterales, local suppurative complications or distant complications due to the same pathogen within 90 days	within 90 days since hopsitalization
length of stay in hospital	length of stay in hospital	from the admission up to the discharge
re-admission to hospital within 90 days	re-admission to hospital within 90 days	within 90 days since discharge

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 6, 2024
• First Posted (Actual): February 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: ASP BSI Protocol

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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