Neurotoxicity risk associated with cefepime versus piperacillin – tazobactam in hospitalized patients with pneumonia: a real-world cohort study

BACKGROUND Cefepime (FEP) and piperacillin – tazobactam (TZP) are antipseudomonal β-lactams widely prescribed for pneumonia. Although FEP-associated neurotoxicity is increasingly recognized, comparative safety data remain limited, particularly outside critical care settings.RESEARCH DESIGN AND METHODS This single-center retrospective cohort study included adults with pneumonia who received empirical intravenous FEP or TZP at National Taiwan University Hospital (2016–2019). Patients receiving concurrent neurotoxic agents or antibiotic therapy < 48 hours were excluded. The primary outcome was antibiotic-associated neurotoxicity, adjudicated by two pharmacists using the Naranjo scale (score ≥ 5). Firth’s penalized likelihood logistic regression examined the antibiotic-neurotoxicity association.RESULTS Among 842 patients (FEP, 137; TZP, 705), neurotoxicity occurred in 5 (3.7%) FEP-treated and 1 (0.1%) TZP-treated patients (p = 0.0006). In an exploratory, unadjusted analysis, FEP exposure was associated with neurotoxicity (OR 19.50, 95% CI 3.17–120.01; p = 0.0014). However, the wide confidence interval and likely under-ascertainment of the outcome – delirium and the highest-risk patients were excluded – render these estimates exploratory.CONCLUSIONS FEP may be associated with a higher neurotoxicity risk than TZP in hospitalized patients with pneumonia; however, given the single-center design and very small number of events, these findings should be regarded as exploratory and hypothesis-generating rather than confirmatory.