Impact of Inappropriate Empirical Antibiotic on Outcomes in Community-acquired Third Generation Cephalosporin Resistant Enterobacterales Bacteremia

BACKGROUND: Currently, third generation cephalosporin resistant Enterobacterales (3GCRE) are becoming more common in community-acquired infection, leading to increasing consumption of carbapenems. Because community-acquired 3GCRE infections are generally less severe and of lower pathogenicity, the impact of inappropriate empirical antibiotics among patients with community-acquired 3GCRE bacteremia remains unknown. MATERIALS AND METHODS: This prospective cohort study included adult patients with 3GCRE bacteremia from April 2018 to December 2021. Participants were followed for 30 days to measure the primary outcome of mortality. Propensity score analysis was performed to adjust for treatment selection bias. RESULTS: A total of 155 patients met the eligible criteria (42 participants in the appropriate antibiotics group, and 113 participants in the inappropriate antibiotics group). Eight participants in the inappropriate antibiotics group never received appropriate antibiotics, three of whom died before microbiological results were made available. The most common clinical syndromes were urinary tract infection (56.8%) and biliary tract infection (22.6%). The overall 30-day mortality rate was 12.9%, 14.3% in the appropriate empirical antibiotics group and 12.4% in the inappropriate empirical antibiotics group. After propensity score weighted adjustment, the 30-day mortality rate in the inappropriate group was non-inferior to the appropriate group (mean difference 1.9%; 95% confidence interval: -10.1 - 14.0). From the multivariate analysis, acute respiratory failure and primary bacteremia were associated with 30-day mortality. CONCLUSION: Among patients with community-acquired 3GCRE bacteremia, inappropriate empirical treatment given within 24 hours after the onset of bacteremia was non-inferior to appropriate antibiotics. In the setting of a high prevalence of 3GCRE carriage in community, adjustment to carbapenem might be tolerable among patients with community-acquired infections. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03765749