Association of different piperacillin/tazobactam ratios and dosages with the risk of hypokalemia: a propensity score-matched retrospective cohort study.

Background: To investigate the association of different piperacillin/tazobactam (TZP) ratios and dosages with hypokalemia, to characterize hypokalemia-related disproportionality signals for selected penicillin-class antibiotics, and to discuss potential mechanistic explanations in relation to chemical structure, with the aim of providing evidence for rational clinical medication use. Methods: This single-center retrospective cohort study included hospitalized patients who received TZP at the First People's Hospital of Zunyi between January 1, 2020 and January 25, 2025. TZP ratio and dosage were defined as exposure variables, and hypokalemia (serum potassium <3.5 mmol/L after TZP initiation) was the clinical outcome. Propensity score matching (PSM) was used to balance measured baseline characteristics, laboratory parameters, infection sites, and concomitant medication categories. In addition, reports involving selected penicillin-class antibiotics were retrieved from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). Reporting odds ratio (ROR), proportional reporting ratio (PRR), and corresponding 95% confidence intervals (95% CIs) were calculated to identify disproportionality signals; these measures were interpreted as reporting signals rather than incidence, clinical risk, or causality. Results: A total of 1,825 patients treated with TZP were included. In the ratio comparison, 678 patients received TZP at a ratio of 8:1 and 716 received TZP at a ratio of 4:1. In the dosage comparison, 678 patients received TZP 3.375 g q8h and 431 received TZP 4.5 g q8h. After 1:1 PSM, 1,356 patients were matched in the ratio groups, with 678 patients in each group, and the incidence of hypokalemia did not differ significantly (33.186% vs. 33.481%; Conclusion: Within this TZP-treated cohort, the 8:1 and 4:1 component ratios were not associated with a detectable difference in hypokalemia incidence, whereas the 4.5 g q8h regimen was associated with a higher observed incidence than the 3.375 g q8h regimen after matching. FAERS findings support the presence of hypokalemia reporting signals for TZP and ampicillin but do not establish comparative clinical risk or causality. These observations support careful serum potassium monitoring during TZP therapy, particularly with higher-dose regimens.