Introduction: Cefepime (FEP) has been associated with neurotoxicity, often at high doses and in patients with renal dysfunction or pre-existing seizure disorders. In this study, we compared neurologic and survival outcomes between FEP and ceftriaxone (CTX) in ICU patients with urinary tract infection and severe sepsis. Methods: Using TriNetX, a federated health research network, we identified adults admitted to the ICU from 2010 to 2024 with UTI and severe sepsis and treated with either FEP or CTX. Patients were identified using ICD-10, CPT, and RxNorm codes. Exclusion criteria: pre-existing neoplasms, concomitant pneumonia, pressure ulcers. Cohorts were propensity-score matched by demographics, comorbidities including cardiovascular disease, dementia, and epilepsy, and antiepileptic drug use. Outcomes assessed at 1 month included seizures, convulsions, encephalopathy, myoclonus and all-cause mortality. Statistical analyses, including risk/odds ratios, Kaplan-Meier survival curves, and regression-based hazard ratios, were performed via TriNetX’s built-in analytics. Abstract drafted with assistance of large language model. Results: After matching, 4080 patients remained in each cohort. At 1 month, there was a slightly increased risk of convulsions in patients treated with FEP (3.6%) vs CTX (2.7%) (OR 1.32, p=0.031). There was no statistically significant increase in seizures (2.5% vs 2.2%, OR 1.16, p=0.307), myoclonus (0.3% vs 0.2%, OR = 1.30, p=0.531), delirium (1.7% vs 1.4%, OR 1.15, p=0.421), or encephalopathy (14.0% vs 12.8%, OR 1.10, p=0.119) in patients treated with FEP vs patients treated with CTX. All-cause mortality was higher in the FEP group (1-month HR 1.82, p=0.042). Conclusions: In this study of ICU patients with urosepsis, FEP was not associated with a significant increase in seizures, myoclonus, delirium, or encephalopathy compared to CTX, although it was associated with a small increase in convulsions. Mortality was higher in the cefepime group, potentially reflecting residual confounding. These findings suggest that cefepime, when dosed appropriately and without predisposing factors, may not carry a clinically significant excess risk of neurotoxicity in ICU patients hospitalized for urosepsis. This study demonstrates in a large cohort study what anecdotal evidence has previously suggested.
Peverini et al. (Sun,) studied this question.