Impact of corticosteroids on lung antibiotic resistance genes in patients with lower respiratory tract infections

Lower respiratory tract infections (LRTIs) are a major global health concern, complicated by rising antibiotic resistance driven by antibiotic resistance genes (ARGs). Despite its role in the treatment of respiratory diseases, the impact of corticosteroids on ARGs in LRTI patients remains underexplored. Bronchial alveolar lavage (BAL) samples were collected from LRTI patients from two intensive care units (ICUs). Patients were classified into the corticosteroid group (CS group) and the non-corticosteroid group (NCS group) based on corticosteroid use. Next-generation sequencing assessed ARGs and associated microbes, with multivariable logistic regression analyzing the relationship between corticosteroid therapy and ARG accumulation. Ninety-one patients were recruited; the CS group ( n = 57) exhibited a distinct ARG profile, marked by higher alpha-diversity and increased prevalence of ARGs than the NCS group ( n = 34). The duration of corticosteroid therapy was positively associated with ARG accumulation, with individuals receiving treatment for more than 30 days exhibiting the highest ARG burden. The duration of corticosteroid therapy and the underlying hematological diseases were two independent risk factors for ARG accumulation. Our data provide new evidence that, in patients with LRTIs, extended corticosteroid use is associated with the accumulation of ARGs and modifications in the microbial composition of the lower respiratory tract.

IMPORTANCE

This research provides new evidence that prolonged use of corticosteroid drastically increases antibiotic resistance genes (ARGs) in the lungs of LRTI patients. It reveals a duration-dependent accumulation of ARGs, notably for common broad-spectrum antibiotics. These findings highlight the need to consider ARG burden when evaluating corticosteroid prescribing practices in patients with lower respiratory tract infections.