Active surveillance and risk prediction of piperacillin/tazobactam‑associated hypokalaemia: development and external validation of a clinical nomogram

Piperacillin/tazobactam (TZP) is widely used in hospitalised adults. Real‑world data suggest a higher risk of hypokalaemia than previously recognised.

To investigate incidence, severity and risk factors of TZP‑induced hypokalaemia, and to develop and externally validate a nomogram for individualised risk prediction.

This retrospective study included hospitalised adults receiving TZP (2021-2025). TZP‑induced hypokalaemia was defined as serum potassium < 3.5 mmol/L ≥ 48 h after TZP initiation. Logistic regression identified predictors. A nomogram was constructed. Model performance was assessed by discrimination (area under the ROC curve, AUC), calibration (Hosmer‑Lemeshow test, calibration intercept/slope), Brier score and decision‑curve analysis (DCA), with internal and external validation.

Among 643 patients, 122 (19.0%) developed TZP‑induced hypokalaemia (mild: 78.7%; moderate: 16.4%; severe: 4.9%). Median time to onset was 5.0 days. Independent predictors were age ≥ 65 years (OR = 2.118, 95% CI 1.003-4.472, p = 0.049), body mass index (OR = 0.671, 95% CI 0.591-0.762, p < 0.001), intensive care unit admission (OR = 2.915, 95% CI 1.504-5.651, p = 0.002), daily dose (OR = 1.280, 95% CI 1.110-1.476, p < 0.001), and baseline serum potassium (OR = 0.123, 95% CI 0.056-0.271, p < 0.001). The nomogram showed good discrimination (training AUC 0.881, internal 0.876, external 0.813), calibration (Hosmer‑Lemeshow p > 0.05), Brier scores < 0.25 and positive net benefit on DCA.

TZP‑induced hypokalaemia is common in hospitalised adults. A nomogram based on five readily available clinical variables may facilitate early identification of high‑risk patients, although prospective validation in diverse settings is required before clinical implementation.