Effects of antibiotic duration on the intestinal microbiota and resistome

Background: Antibiotic overuse is one of the major causes of the increase of antibiotic resistance. The effect of antibiotic treatment on gut microbiota from patients randomized to different antibiotic durations has never been investigated. In present work, we challenged the hypothesis according to which halving the duration of antibiotic therapy should prevent from the selection of antibiotic resistance genes compared to long treatments.Methods: we analysed by whole metagenome shotgun sequencing the faecal microbiota profiles from 44 patients included in “the Point-of-care, informatics-based randomised controlled trial for decreasing overuse of antibiotic therapy in Gram-negative bacteraemia” (PIRATE) trial. Patients were administered with antibiotics against Gram-negative bacteremia either for 7±2 or 14 ±3 days. Sequencing reads were mapped to bacterial species reference genomes and queried against ResFinder database for detection of antibiotic resistance genes (ARGs). Findings: we detect genetic resistance several days after the termination of antibiotic therapy irrespective of treatment duration. We did not find significant differences in microbiota profile between short-term and long-term treated patients. Recovery of microbiota from antibiotic therapy resulted in a significant increase in butyrate-producing species.Interpretation: Shorter antibiotic courses does not result in a decreased emergence of ARGs in the intestinal microbiome overall compared to longer treatments.