ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1622392
Piperacillin-Tazobactam-Associated Leukopenia: A Retrospective Cohort Analysis and Mechanistic Study of Risk Factors and Autophagy Signaling Pathways
Provisionally accepted
Wenzhen Dai*
Li Zeng- Bishan hospital of Chongqing Medical University, Chongqing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Background: Piperacillin-tazobactam (PTZ), a β-lactam/β-lactamase inhibitor combination, is widely used for severe infections but is associated with leukopenia. This study aimed to identify clinical risk factors and molecular mechanisms of PTZ-associated leukopenia. Methods: A retrospective cohort study of 263 PTZ-treated patients assessed demographic, clinical, and treatment-related risk factors. Logistic and Cox regression analyses evaluated leukopenia and delayed leukocyte recovery. In vitro experiments examined PTZ effects on HL-60 cell proliferation, apoptosis, differentiation, and transcriptomic profiles. Results: Advanced age (≥65 years, OR=1.78), kidney dysfunction (eGFR <60 mL/min/1.73m², OR = 2.12), diabetes mellitus (OR = 1.67), high cumulative PTZ dose (≥200 g, OR=2.05), prolonged duration (≥10 days, OR = 2.33), and combination therapy (PTZ with other antibiotics, OR = 2.18) were independent risk factors. High-dose and prolonged therapy delayed leukocyte recovery (HR=2.08 and 2.25). PTZ inhibited HL-60 proliferation via G1 arrest, promoted apoptosis, and enhanced differentiation. Transcriptomic profiling indicated significant enrichment of autophagy signaling in PTZ-treated HL-60 cells. Conclusions: PTZ-associated leukopenia involves patient-specific vulnerabilities, dose-dependent toxicity, and autophagy-mediated apoptosis. Personalized dosing and monitoring are critical to mitigate risks.
Keywords: Piperacillin-tazobactam, Retrospective cohort study, Leukopenia, Autophagy signaling pathway, proliferation, Apoptosis
Received: 03 May 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Dai and Zeng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenzhen Dai, Bishan hospital of Chongqing Medical University, Chongqing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.