Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis

Study Overview
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Brief Summary
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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 within 48 hours.

Official Title
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Integrated Clinical Decision Support for Empiric Antibiotic Selection in Sepsis: A Cluster Randomized Cross-Over Trial (IDEAS-CRXO)

Conditions
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Sepsis, Bacterial Infections, Community-Acquired Infections, Hospital Infection

Intervention / Treatment
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* Other: Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted Age >18 years old Newly started (within 24 hours of assessment for eligibility) on at least one of the following antibiotic(s): I. Vancomycin II. Linezolid III. Daptomycin IV. Cefazolin V. Cloxacillin VI. Ceftriaxone VII. Ceftazidime VIII. Piperacillin-Tazobactam IX. Meropenem (or Imipenem or Ertapenem) X. Ciprofloxacin (or Moxifloxacin or Levofloxacin) XI. Gentamicin (or Tobramycin). Blood cultures ordered (within 12 hours before or after initiation of antibiotics). Exclusion Criteria: Documented end-of-life (palliative) care. Already enrolled in the trial. Positive clinical culture results for the index infection already available prior to giving advice. Receipt of antimicrobials (not chronic suppression) in the prior 24-72 hours.

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: Crossover Assignment
Interventional Model Description: Cluster Randomized Cross-Over Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis<br>The planned intervention consists of a pharmacist-facilitated clinical decision support intervention, where pharmacists provide options and recommendations on empiric sepsis antibiotic selection to hospital providers. | Other: Clinical Decision Support Algorithm for Empiric Antibiotics in Sepsis<br>* A clinical decision support algorithm for empiric antibiotic selection in suspected infection.<br>* Other names: Decision Support Tool;|
| No Intervention: Standard of Care<br>Non-intervention group. No decision support is provided. Patient care is routine. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients De-escalated | De-escalation from empiric antibiotic regimen within 48 hours of receipt of antibiotics [Binary]. | 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to adequate therapy | Time to adequate therapy for patients with positive blood cultures (hours from time of blood culture collection to first dose of agent(s) active against all pathogen(s) in the positive culture). | 0-7 days | 
| Number of Patients Receiving Adequate Therapy at 48 hours | Receipt of adequate antibiotic therapy within 48 hours from blood culture collection for patients with positive cultures. | 48 hours | 
| Mortality | In-hospital mortality, during index admission, and within 90 days of index event. | 90 days | 
| Length of stay | Hospital length of stay on index admission (days). | 0-90 days | 
| De-escalation extent | Extent of antibiotic de-escalation (ordinal value up or down the de-escalation cascade) | 48 hours | 
| Antibiotic spectrum at completion | Antibiotic spectrum ranking on the last day of antibiotic treatment. | Completion of therapy, up to 90 days | 
| C.difficile Infection | Positive stool testing for C. difficile during index admission, and within 90 days of index. | 90 days | 
| Dialysis | New requirement for dialysis during index admission, and within 90 days of index. | 90 days | 
| Days of antibiotic therapy | Total antibiotic days of therapy (DOT) during index admission, including by spectrum-level. | End of index admission, up to 90 days | 
| Escalation | Newly started Gram-positive or Gram-negative coverage, or increases in spectrum of antibiotic therapy, as part of the intervention recommendation. | 48hrs | 
| Recommended change in Gram-negative coverage | Recommended change in antibiotic therapy by Gram-negative model. | At time of assessment | 
| Accepted change in Gram-negative coverage | Recommended change in antibiotic therapy by Gram-negative model was accepted and ordered. | At time of assessment | 
| Recommended change in Gram-positive coverage | Recommended change in antibiotic therapy by Gram-positive algorithm. | at time of assessment | 
| Accepted change in Gram-positive coverage | Recommended change in antibiotic therapy by Gram-positive algorithm was accepted and ordered. | At 48 hrs | 
| Non-recommended escalation at 7 days | Escalation of antibiotic therapy (apart from recommended escalation) within 7 days of receipt of initial antibiotics | 7 days | 
| ICU admit or mortality | ICU admission or death at 7 days from receipt of initial antibiotics | 7 days |