Association between tazobactam-piperacillin exposure and the subsequent emergence in gram-negative rods: Findings from a single-institution cohort study.

BACKGROUND: The impact of tazobactam-piperacillin (TZP) exposure on subsequent resistance development remains unclear. We evaluated the association between TZP treatment duration and the emergence of TZP-resistant gram-negative rods (GNRs). METHODS: This single-institution retrospective observational study included all patients who received TZP at Toyama University Hospital (January 2021-December 2023). The primary outcome was the emergence of new TZP-resistant GNRs of interest, including Pseudomonas aeruginosa and Enterobacterales, within 180 days of the index exposure. Death was treated as a competing risk. Multivariable Fine-Gray regression analysis identified independent risk factors. RESULTS: Among 1,619 patients treated with TZP, 96 (5.9%) developed new TZP-resistant GNRs within 180 days. The cumulative incidence was higher in patients exposed to TZP for ≥14 days (12.0%). TZP-resistant isolates comprised P. aeruginosa (28%) and AmpC-producing Enterobacterales (42%). In multivariable analysis, prolonged TZP exposure (≥14 days) was independently associated with resistance emergence (adjusted subdistribution hazard ratio 1.73; 95% confidence interval 1.03-2.89). Additional independent risk factors included the initial isolation of P. aeruginosa or AmpC-producing Enterobacterales without baseline TZP resistance and specific infection foci or clinical conditions. CONCLUSIONS: Prolonged TZP exposure (≥14 days) was an independent risk factor for the subsequent emergence of TZP-resistant GNRs. Baseline microbiological characteristics also influenced resistance development. These findings support optimization of TZP treatment duration within antimicrobial stewardship programs to mitigate resistance emergence.