Effective Antimicrobial StewaRdship StrategIES (ARIES)

Study Overview
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Brief Summary
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Background Prospective review and feedback (PRF) of antibiotic prescriptions is a labor-intensive core strategy of antimicrobial stewardship (AMS). The investigators hypothesized that a computerized decision support system (CDSS) providing recommendations for antibiotics, investigations and referrals would reduce the requirement for PRF without causing harm. Methods A parallel-group, 1:1 block-cluster randomized, cross-over study was conducted in 32 medical and surgical wards from March to August 2017. The intervention arm comprised voluntary use of CDSS at first prescription of piperacillin-tazobactam or a carbapenem, while the control arm was compulsory CDSS. PRF was continued for both arms. Primary outcome was 30-day mortality.

Detailed Description
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Increasing antimicrobial resistance due to inappropriate antimicrobial use is a global concern. Multi-disciplinary antimicrobial stewardship teams have become an integral part of the response to this issue. Through prospective review of antibiotic prescriptions and feedback (PRF) to healthcare providers, antimicrobial stewardship has been shown to improve clinical response, reduce adverse effects and mortality. However, this strategy is labor-intensive to implement and skilled healthcare workers are an expensive and scarce resource. Antibiotic computerized decision support systems (CDSS) have been used to facilitate these processes and may circumvent the limitations of lack of manpower. In previous studies, CDSS led to increased susceptibility of Pseudomonas aeruginosa to imipenem and Enterobacteriaceae to gentamicin and ciprofloxacin, and an overall reduction in broad-spectrum antibiotic use. CDSS could improve clinical outcomes. Currently, there are limited studies comparing the combined effects of these two strategies. At Tan Tock Seng Hospital, a university teaching hospital in Singapore, antimicrobial stewardship has focused on PRF by a multi-disciplinary team since 2009. This team reviews piperacillin-tazobactam and carbapenem orders against hospital antibiotic guidelines from day two of antibiotic prescription. In March 2010, we implemented CDSS triggered at the point of antibiotic ordering and compulsory for the prescriber to review. Prescribers are free to accept or reject the CDSS recommendations. While PRF and CDSS are performed following the same institutional guidelines, there may be differences in physicians' acceptance of recommendations and the accessibility to recommendations between these two interventions. In previous studies, PRF recommendations had an acceptance of 60-70% while compulsory CDSS was 40%. The investigators hypothesized that compulsory CDSS and PRF would improve clinical outcomes compared with voluntary CDSS and PRF, and compulsory CDSS would improve appropriate antibiotic practice and reduce the requirement for subsequent PRF.

Official Title
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Effective Antimicrobial StewaRdship StrategIES (ARIES): Cluster-randomized Trial of a Computerized Decision Support System Versus Antibiotic Prospective Review and Feedback in Antimicrobial Stewardship

Conditions
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Infection, Bacterial

Intervention / Treatment
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* Other: Compulsory CDSS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are started on the 1st episode of piperacillin-tazobactam or carbapenem during the study period. Medical and surgical wards Exclusion Criteria: Intensive care unit (ICU), high dependency and step-down care wards

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: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Voluntary CDSS<br>Voluntary use of computerized decision support with prospective review and feedback | Other: Compulsory CDSS<br>* Compulsory CDSS use with prospective review feedback in patients prescribed with piperacillin tazobactam or carbapenems<br>|
| No Intervention: Compulsory CDSS<br>Compulsory use of computerized decision support with prospective review and feedback | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day mortality | Death at 30 days | Follow-up up to 30 days from the start date of the first episode of piperacillin-tazobactam or carbapenem use | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day clinical response | resolution of systemic inflammatory response syndrome | Follow-up up to 7 days from the date of the first episode of piperacillin-tazobactam or carbapenem use | 
| 30-day re-infection | Re-start of piperacilin-tazobactam or carbapenem 30 days after the cessation of first episode of piperacillin-tazobactam or carbapenem use | Re-start of piperacilin-tazobactam or carbapenem 30 days after the cessation of first episode of piperacillin-tazobactam or carbapenem use | 
| 30-day readmission | Readmission after the cessation of first episode of piperacillin-tazobactam or carbapenem use | Readmissions 30 days after the cessation of first episode of piperacillin-tazobactam or carbapenem use | 
| length of stay | Duration of admission | It is assessed from the date of admission till the date of discharge or up to 6 months | 
| 6-months incidence of multi-drug resistant organisms | MRSA, VRE, ESBL, MDR-A. baumannii, XDR- A baumannii, MDR- P. aeruginosa, XDR-P aeruginosa, C difficile , Carbapenem resistant enterobacterales | up to 6 months (Clinical cultures only) | 
| Diarrhea this admission | Incidence of diarrhea from start of first episode of piperacillin-tazobactam or carbapenem use till discharge | From the start date from the first episode of piperacillin-tazobactam or carbapenem use until the discharge date or up to 6 months whichever occurred earlier | 
| Appropriateness of antibiotics | first episode of piperacillin-tazobactam or carbapenem use according to hospital guidelines. Appropriateness will be described as yes or no. | It is assessed only once at the point of the first episode of piperacillin-tazobactam or carbapenem use in the index admission. It is only assessed once till discharge or up to 6 months | 
| Index antibiotic days of therapy, | Duration of the first episode of piperacillin-tazobactam or carbapenem use | From the start date of the first episode of piperacillin-tazobactam or carbapenem use to the end date of this antibiotic which is followed up till discharge or up to 6 months. | 
| Gross hospitalization costs | Gross hospitalization costs | Gross hospitalization costs incured from date of admission till date of discharge or up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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computerized decision support, prospective review and feedback, antimicrobial stewardship