Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorOttawa Hospital Research Institute

About this trial

As antibiotic resistance increases globally, it becomes more difficult to select empiric antibiotic therapy, particularly in patients with sepsis who stand to benefit from early adequate treatment. In particular it is difficult for clinicians to balance antibiotic stewardship principles (the need to avoid unnecessary prescribing of antibiotics that have an excessively broad spectrum of activity that favour resistance development) and under treatment. The integration of multiple risk variables for resistance are hard for clinicians to translate into clinical action, and is seemingly at odds with the natural inclination to provide heuristic/emotion-based antibiotic selection. The inappropriate treatment of sepsis is not uniformly too broad, or too narrow, and there is a need to optimize and tailor selection of antibiotic therapy to each patient, such that those that are at risk for resistant organisms receive broad therapy, and those that are not at risk, receive narrower antibiotic agents.

Clinicians need support picking the right antibiotic for each patient, and from this they can potentially drive reduction of unnecessarily broad antibiotic prescribing while preserving adequacy of treatment. Individualized clinical prediction models and decision support interventions are promising approaches that meet these needs by improving the classification of patient risk for antibiotic resistant or susceptible infections in sepsis. Unfortunately, few have been validated in the clinical setting and larger rigorous studies are needed to provide the evidence to support broader clinical adoption.

The investigators will perform a cluster randomized cross-over trial of an individualized antibiotic prescribing decision support intervention for providers treating hospitalized patients with suspected sepsis. The aim of this trial is to determine whether a stewardship led clinical decision support intervention can improve antibiotic de-escalation in patients with sepsis while maintaining or improving adequacy of antibiotic coverage. This decision support intervention will be based on a combination of proven decision heuristics (for Gram-positive organisms) and modelled predicted susceptibilities (for Gram-negative organisms) that are individualized to the patient. The primary outcome will be the proportion of patients de-escalated from their initial empiric regimen at 48 hours.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Admitted

Age >18 years old

Blood cultures ordered (within 12 hours before or after initiation of index antibiotics).

Pregnancy/breastfeeding

Disqualifiers

Explanatory molecular test (e.g. legionella urinary antigen test, sars-cov-2 testing) within 72 hours prior to assessment.

Receipt of antimicrobials (not chronic suppression or prophylaxis) in the prior 24-72 hours (except if started in the outpatient setting or ED prior to admission in the 24-72 hours).

The index prescription is a continuation of an antibiotic given for suppressive chronic therapy or long-standing treatment of an established infection.

Index antibiotics are peri-operative only or ordered for <24 hours.

Trial design

Design model

Crossover

Treatments tested in this trial

  • Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis

    Other intervention

    A clinical decision support algorithm for empiric antibiotic selection in suspected infection.

Treatment groups

1,440 Participants
are divided into 2 treatment groups
Group A: Clinical Decision Support Algorithm for Empiric Antibiotics in SepsisExperimental treatment 1 intervention
Group B: Standard of CareNo intervention 0 interventions

Trial outcomes

Primary outcomes

1

Number of Patients De-escalated

De-escalation from empiric antibiotic regimen at 48 hours (or at time of discharge if earlier) from receipt of index antibiotics \[Binary\].

Time frame
48 hours

Secondary outcomes

1

Time to adequate therapy for positive blood cultures

Time to adequate therapy for patients with positive blood cultures (hours from time of first index blood culture collection to first dose of agent(s) active against all pathogen(s) in the peri-index positive blood cultures). \[Continuous\] \[Stratified by ampC organisms\]

Time frame
0-7 days
2

Time to adequate therapy for positive non-screening cultures

Time to adequate therapy for patients with positive non-screening cultures including blood cultures (hours from time of first index blood culture collection to first dose of agent(s) active against all pathogen(s) in the peri-index positive cultures). \[Continuous\]\[Stratified by ampC organisms\]

Time frame
0-7 days
3

Number of Patients Receiving Adequate Therapy at 48 hours based on blood cultures

Receipt of adequate antibiotic therapy within 48 hours (or discharge if earlier) from first index blood culture collection for patients with positive blood cultures (active against all pathogens in peri-index positive blood cultures). \[Binary\]

Time frame
48 hours
4

Number of Patients Receiving Adequate Therapy at 48 hours based on non-screening cultures

Receipt of adequate antibiotic therapy within 48 hours (or discharge if earlier) from first index blood culture collection for patients with positive non-screening cultures including blood (active against all pathogens in peri-index positive cultures). \[Binary\]

Time frame
48 hours

Other outcomes

Sponsors and contacts

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Ottawa Hospital Research Institute

Lead sponsor

Canadian Institutes of Health Research (CIHR)

Collaborator