Short- versus long-course antibiotic therapy for sepsis: a post hoc analysis of the nationwide cohort study.

Background: The appropriate duration of antibiotic treatment in patients with bacterial sepsis remains unclear. The purpose of this study was to evaluate the association of a shorter course of antibiotics on 28-day mortality in comparison with a longer course using a national database in Japan. Methods: We conducted a post hoc analysis from the retrospective observational study of patients with sepsis using a Japanese claims database from 2010 to 2017. The patient dataset was divided into short-course (≤ 7 days) and long-course (≥ 8 days) groups according to the duration of initial antibiotic administration. Subsequently, propensity score matching was performed to adjust the baseline imbalance between the two groups. The primary outcome was 28-day mortality. The secondary outcomes were re-initiated antibiotics at 3 and 7 days, during hospitalization, administration period, antibiotic-free days, and medical cost. Results: After propensity score matching, 448,146 pairs were analyzed. The 28-day mortality was significantly lower in the short-course group (hazard ratio, 0.94; 95% CI, 0.92–0.95; P < 0.001), while the occurrence of re-initiated antibiotics at 3 and 7 days and during hospitalization were significantly higher in the short-course group (P < 0.001). Antibiotic-free days (median [IQR]) were significantly shorter in the long-course group (21 days [17 days, 23 days] vs. 17 days [14 days, 19 days], P < 0.001), and short-course administration contributed to a decrease in medical costs (coefficient $-212, 95% CI; − 223 to − 201, P < 0.001). Subgroup analyses showed a significant decrease in the 28-day mortality of the patients in the short-course group in patients of male sex (hazard ratio: 0.91, 95% CI; 0.89–0.93), community-onset sepsis (hazard ratio; 0.95, 95% CI; 0.93–0.98), abdominal infection (hazard ratio; 0.92, 95% CI; 0.88–0.97) and heart infection (hazard ratio; 0.74, 95% CI; 0.61–0.90), while a significant increase was observed in patients with non-community-onset sepsis (hazard ratio; 1.09, 95% CI; 1.06–1.12). Conclusions: The 28-day mortality was significantly lower in the short-course group, even though there was a higher rate of re-initiated antibiotics in the short course. [ABSTRACT FROM AUTHOR]