Association between in-hospital antibiotic use and long-term outcomes in critically ill patients.

Objective: To assess whether antibiotic duration (AD) and one-year antibiotic-free days (AFD) are associated with key in-hospital and post-discharge outcomes among critically ill adults.

Design: Prospective observational study.

Setting: 611-bed, quaternary care academic medical center in the United States.

Patients: 126 critically ill adults (mean age 68.1 ± 15.6 yr, 51.6% male, median APACHE II score 20.5 [IQR 15-25]); 71.4% met sepsis criteria.

Methods: Secondary infection was defined as ≥3 consecutive antibiotic days within a year after the index sepsis admission. Multivariate analyses adjusted for age, APACHE II score, BMI, and glucocorticosteroid dose. Time-to-event analysis employed Cox proportional hazards modeling; cumulative infection burden was assessed via nonparametric tests using normalized antibiotic exposure (AD as a proportion of days alive).

Results: Within 30 days, longer AD correlated with increased hospital stay; each additional antibiotic day added ∼0.93 hospital days (P < 0.001) in adjusted linear regression. AD did not predict one-year mortality (OR 1.01, P = 0.739) or readmission (OR 1.01, P = 0.771). Normalized antibiotic exposure significantly differed by cumulative secondary infection episodes (P = 0.0033), with higher exposure among patients experiencing two or more secondary infections (P = 0.026 and P = 0.036, respectively). Cox regression showed a significant association between AD and time to first secondary infection (HR 1.10, 95% CI: 1.04-1.15, P = 0.001), indicating that longer AD predisposed to secondary infection or recurrent antibiotic use.

Conclusions: Extended AD, in critically ill patients, prolongs hospitalization without reducing mortality or readmission rates. These findings highlight the importance of robust antibiotic stewardship practices, where shorter, targeted regimens may minimize unintended complications.