International journal of antimicrobial agents · 2026
Association between tazobactam-piperacillin exposure and the subsequent emergence in gram-negative rods: Findings from a single-institution cohort study.
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Masayoshi Ezaki, Noriko Kato, Kentaro Nagaoka, Yushi Murai, Kazushige Sugie, Yusuke Kamihara, Hiroyuki Hounoki, Toru Watanabe, Toshiomi Kawagishi, Naohiro Yonemoto, Hitoshi Kawasuji, Hideki Niimi, Yoshitomo Morinaga, Yuki Ohama, Yukihiro Akeda, Yoshihiro Yamamoto
Аннотация
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 1619 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.
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 1619 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.