Impact of High-Dose Cefepime During the Initial 48 h on Intensive Care Unit Survival in Sepsis: A Retrospective Observational Study

<b>Background/Objectives:</b> Sepsis is a life-threatening condition associated with high mortality. Optimal dosing strategies for β-lactam antibiotics in sepsis remain controversial, particularly in patients with renal impairment. Cefepime (CFPM) is widely used as empiric therapy; however, its appropriate initial dosing in critically ill patients is unclear. This study aimed to evaluate whether high-dose CFPM administration during the first 48 h improves survival in patients with sepsis, irrespective of renal function. <b>Methods:</b> This single-center, retrospective, observational study included adult intensive care unit (ICU) patients with sepsis who received CFPM as initial therapy between January 2017 and December 2024. Patients were categorized into High-dose (12 g within 48 h; 2 g every 8 h) and Low-dose (<12 g/48 h) groups. The primary outcome was ICU survival. To address confounding, inverse probability of treatment weighting (IPTW) based on serum creatinine was applied, with sensitivity analyses using 1% trimmed and stabilized IPTW. <b>Results:</b> Of 122 eligible patients, 84 were analyzed (High-dose: n = 27; Low-dose: n = 57). After IPTW adjustment, high-dose CFPM was significantly associated with improved ICU survival (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.60-18.39, <i>p</i> = 0.0066). This association remained consistent in the 1% trimmed IPTW analysis (OR 4.07, 95% CI 1.19-13.97, <i>p</i> = 0.0256). Stabilized IPTW yielded a similar effect estimate, though without statistical significance (OR 5.43, 95% CI 0.72-41.16, <i>p</i> = 0.1017). Overall, results were consistent in direction and magnitude across models. <b>Conclusions:</b> High-dose CFPM administration during the initial 48 h was associated with improved ICU survival in patients with sepsis, independent of renal function.