Evaluation of antioxidant co-therapy for polymyxin B-associated nephrotoxicity and mortality: a real-World...

Polymyxin B is increasingly used to treat infections caused by multidrug-resistant gram-negative bacteria; however, its widespread clinical use is hindered by the high incidence of nephrotoxicity. Antioxidants, such as vitamin C, N-acetylcysteine (NAC), and methionine, have demonstrated renoprotective effects in preclinical models, although clinical evidence remains limited. This study aimed to investigate the potential protective effects of these antioxidants against polymyxin B-associated acute kidney injury (AKI) in real-world clinical practice.

This retrospective cohort study included adult in patients who received intravenous polymyxin B for ≥ 3 days between August 2018 and August 2020. The patients were classified into an antioxidant group (co-administered vitamin C, NAC, or methionine for ≥ 3 days) or a control group. Propensity score weighting was applied to balance the baseline covariates. The primary outcome was the incidence of polymyxin B-associated AKI and the secondary outcome was discharge mortality.

A total of 321 patients were included, with 77 and 244 patients in the antioxidant and control groups, respectively. After propensity score adjustment, there were no statistically significant differences in AKI incidence (26.9% vs. 19.2%, P = 0.352) or discharge mortality (7.7% vs. 15.4%, P = 0.220) between the groups. Subgroup analyses of individual antioxidants also showed no significant differences in AKI or mortality, except for a lower unadjusted mortality in the methionine group (0% vs. 13.9%, P = 0.042), which lost significance after adjustment.

This exploratory study did not provide conclusive evidence that vitamin C, NAC, or methionine reduced the risk of polymyxin B-associated AKI. The potential association between antioxidant use and reduced mortality warrants further investigation. Large-scale prospective studies are required to confirm the clinical utility of antioxidant cotherapy in patients receiving polymyxin B.