Abstract
Antimicrobial stewardship programs (ASPs) are critical for combating antimicrobial resistance (AMR), yet their longitudinal ecological impacts remain debated. This study evaluated the association between a carbapenem post-prescription audit and the susceptibility of seven Gram-negative bacteria over 6 years. A retrospective interrupted time-series (ITS) study was conducted in a tertiary hospital, comparing pre-implementation (2015-2017) and post-implementation (2018-2020) phases. Autoregressive Integrated Moving Average (ARIMA) modeling was utilized to assess trend modifications and immediate level changes in pathogen susceptibility before and after audit enforcement. The audit was associated with pathogen-specific trend reversals. Proteus mirabilis imipenem susceptibility reversed from a significantly declining baseline to a positive recovery trend post-intervention (β = 9.465, P = 0.005). Conversely, Klebsiella pneumoniae and Pseudomonas aeruginosa experienced significant downward post-intervention trend reversals for targeted carbapenems despite rising baselines. Ecologically, immediate susceptibility gains in third-generation cephalosporins for Acinetobacter baumannii and Escherichia coli contrasted with significant collateral susceptibility declines for fluoroquinolones and β-lactam/ β-lactamase inhibitors, including a severe immediate drop in P. mirabilis susceptibility to amoxicillin-clavulanate (β = - 43.023, P = 0.024). While targeted carbapenem audits are temporally associated with the reversal of specific declining susceptibility trajectories, they may also coincide with the displacement of selective pressure onto broad-spectrum alternatives. Comprehensive ASPs must concurrently monitor total institutional antibiograms to identify and manage this potential ecological displacement.