The aim of the present study was to investigate whether replacement of broad-spectrum cephalosporins (CEPs) by piperacillin/tazobactam (TZP) as first-line empirical therapy may have an effect on β-lactam resistance among Klebsiella pneumoniae and Escherichia coli in a tertiary care hospital. Data regarding CEP and TZP consumption and resistance were collected on a bimonthly basis during an open-label 2-year (1 year observational and 1 year interventional) study. Consumption of ceftazidime was reduced by 64.5%. In contrast, consumption of the other third-generation CEPs (cefotaxime and ceftriaxone) remained almost stable, whereas an increase in consumption of TZP by 2.8-fold was observed. A significant decrease in resistance to third-generation cephalosporins among K. pneumoniae isolates was observed, and the incidence of extended-spectrum β-lactamase-producing isolates was notably reduced. These findings were less evident among E. coli isolates. Despite the significant increase in TZP consumption, the respective resistance rates of both bacterial species examined have remained almost unchanged.

• Quantitative data - Quantitative data were used during the intervention

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• Healthcare delivery