Restriction Evaluation of Appropriate Carbapenem Therapy (REACT): A Multisite Observational Study

Introduction: Overuse of carbapenem antibiotics can lead to patient harm through adverse effects and further development of bacterial resistance. The purpose of this study was to investigate the sustained impact of meropenem restriction criteria on utilization volume and appropriateness. Methods: A retrospective observational study was conducted to evaluate meropenem restriction criteria among 5 adult hospitals (1 academic hospital and 4 community hospitals) in a single health system. Total meropenem days of therapy/1000 patient days (DOT/1000 PDs) and drug spending was compared before (January 2022) and after implementation (July 2023) were reviewed to investigate total impact of restriction criteria in the first year after implementation. Statistical comparisons used t tests or Mann-Whitney U tests for continuous data and chi square or Fisher's exact tests for categorical data; significance was defined as P < 0.05. Results: A total of 161 meropenem orders were included in this study, with 61 (39%) found to be inappropriate based on approved restriction criteria. The top 3 reasons for inappropriate meropenem use were undocumented or non-anaphylactic penicillin allergies (31%), lack of qualifying resistant organism within 3 months (26%), and starting meropenem prior to completing 48 hours of empiric therapy with cefepime or piperacillin/tazobactam (23%). The median meropenem DOT/1000 PD decreased from 40.5 to 20 (P < 0.001). Median monthly drug spend on meropenem across the hospital system decreased by 42% during the study period (P = 0.001). Conclusions: Meropenem restriction criteria across a multi-site health system can sustainably reduce carbapenem use and associated costs, supporting their continued adoption in antimicrobial stewardship policy.