The Relationship Between Antibiotic Administration Timing and Short-Term and Long-Term Prognosis in Elderly Septic Patients

Background: Sepsis management in elderly populations presents unique challenges due to age-related physiological changes and comorbidities. Current guidelines remain conflicted regarding optimal antibiotic timing. We conducted a retrospective, multicenter study to evaluate the association between antibiotic administration timing and short-term and long-term outcomes in elderly sepsis patients. Methods: This retrospective cohort study analyzed data from the MIMIC-IV (v3.1) database. Patients were categorized into the early group (antibiotics initiated within 1 h) and the late group (antibiotics initiated >1 h after diagnosis). Further analyses were stratified by shock status (septic shock vs non-septic shock) and pathogen type (Gram-positive vs Gram-negative bacteria). Multivariable Cox regression assessed associations between antibiotic administration timing and 28-/180-/365-day hospital mortality. Restricted cubic spline models evaluated dose-response relationships. The primary outcome was 28-day hospital mortality. Secondary outcomes included 180-day and 365-day mortality rates, along with the incidence of continuous renal replacement therapy (CRRT) and mechanical ventilation requirements. Results: A total of 12,425 patients met the inclusion criteria from the MIMIC-IV database. The multivariable-adjusted analysis demonstrated that delayed antibiotics administration was significantly associated with a 35% increased risk of 28-day all-cause hospital mortality (HR = 1.35, 95% CI 1.22-1.52; P < 0.001), a 43% elevated 180-day hospital mortality risk (HR = 1.43, 95% CI 1.30-1.56; P < 0.001), and a 45% higher 365-day mortality risk (HR = 1.45, 95% CI 1.33-1.56; P < 0.001). Stratified analyses revealed mortality benefits persisted in non-shock patients (28-day HR = 1.31, P < 0.001) and Gram-positive infections (28-day HR = 1.63, P < 0.001), whereas no significant associations emerged in septic shock (28-day HR = 0.82, 95%CI 0.65-1.03; P = 0.081) or Gram-negative infections (HR = 1.04, 95%CI 0.87-1.24; P = 0.692). A linear relationship was observed between antibiotic delay and mortality (Nonlinear P = 0.88). Conclusions: Early antibiotic administration improves survival in elderly sepsis patients, particularly non-shock cases and Gram-positive infections. These insights advocate the importance of individualized selection based on patients’ clinical context in critical care practice.