| Summary: | Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a critical public health threat, and carbapenem use contributes to their spread. Antimicrobial stewardship programs (ASPs) have proven successful in reducing antimicrobial use. However, evidence on the impact of carbapenem resistance remains unclear. We evaluated the impact of a multifaceted ASP on carbapenem use and incidence of CR-GNB in a high-endemic hospital. An interrupted time-series analysis was conducted one year before and two years after starting the ASP to assess carbapenem consumption, CR-GNB incidence, death rates of sentinel events, and other variables potentially related to CR-GNB incidence. An intense reduction in carbapenem consumption occurred after starting the intervention and was sustained two years later (relative effect −83.51%; 95% CI −87.23 to −79.79). The incidence density of CR-GNB decreased by −0.915 cases per 1000 occupied bed days (95% CI −1.743 to −0.087). This effect was especially marked in CR-<i>Klebsiella pneumoniae</i> and CR-<i>Escherichia coli</i>, reversing the pre-intervention upward trend and leading to a relative reduction of −91.15% (95% CI −105.53 to −76.76) and −89.93% (95% CI −107.03 to −72.83), respectively, two years after starting the program. Death rates did not change. This ASP contributed to decreasing CR-GNB incidence through a sustained reduction in antibiotic use without increasing mortality rates.
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