A noninferiority cluster-randomized controlled trial on antibiotic postprescription review and authorization by trained general pharmacists and infectious disease clinical fellows

Abstract

Objective We compared the effectiveness of antibiotic postprescription review and authorization (PPRA) determined by infectious disease (ID) clinical fellows with that of trained general pharmacists.Methods We conducted a noninferiority cluster-randomized controlled trial in 6 general medical wards at Siriraj Hospital in Bangkok, Thailand. Three wards were randomly assigned to the intervention (ie, the pharmacist PPRA group), and another 3 wards were assigned to the control (ie, the fellow PPRA group). We enrolled all patients in the study wards who received 1 or more doses of the targeted antibiotics: piperacillin/tazobactam, imipenem/cilastatin, and meropenem. The noninferiority margin was 10% for the favorable clinical response and 1.5 defined daily doses (DDDs) for the targeted antibiotics.Results We enrolled 303 patients in the pharmacist PPRA group and 307 patients in the ID fellow PPRA group. The baseline and clinical characteristics were similar in the 2 groups. The difference in the favorable response of patients who received the targeted antibiotics (ie, the pharmacist PPRA group minus the fellow PPRA group) was 5.15% (95% confidence interval [CI], -2.69% to 12.98%); the difference in the DDD of targeted antibiotic use (ie, the pharmacist PPRA group minus the fellow PPRA group) was 0.62 (95% CI, -1.57 to 2.82). We observed no significant difference in the DDD of overall antibiotics, 28-day mortality, 28-day ID-related mortality, favorable microbiological outcome, or antibiotic-associated complications.Conclusions We confirmed the noninferiority of pharmacist PPRA in terms of favorable clinical response; however, noninferiority in targeted antibiotic consumption could not be established. Therefore, using trained general pharmacists rather than ID clinical fellows could be an alternative in a resource-limited setting. Clinical trials registration: clinicaltrials.gov identifier: NCT 01797133 © 2018 by The Society for Healthcare Epidemiology of America. All rights reserved.