Development of antibiotic-associated diarrhoea in sepsis patients is associated with dysbiosis at baseline: Data from the PROGRESS Controlled Trial

OBJECTIVE: The randomized PROGRESS trial (ClinicalTrials.gov NCT03333304) proved that the early stopping of antibiotics in sepsis guided by procalcitonin changes leads, among others, to a decrease in the incidence of antibiotic-associated diarrhoea (AAD) and preservation of gut microbiome diversity. We aimed to explore the association of AAD with baseline microbiome composition. METHODS: Patients with sepsis were followed for 28 d for AAD development. As procalcitonin guidance led to a decrease in AAD, only patients of the comparator arm (i.e. under treatment with standard-of-care duration of antimicrobials) were considered for this exploratory analysis. In the case of diarrhoea, Clostridioides difficile infection was thoroughly investigated and excluded. Faecal samples were collected before initiation of antimicrobials and microbiome analysis was done by 16S rRNA Nanopore sequencing. RESULTS: The Shannon diversity index was similar at baseline in 31 patients with AAD (3.01; Q1-Q3: 2.49-3.49) and 54 patients without AAD (2.83; Q1-Q3: 2.16-3.27; P: 0.456). Relative abundance of Bacillota was lower (P: 0.038) in patients with AAD, and the relative abundance of Pseudomonadotawas higher (P: 0.019) in patients with AAD. Abundance of the butyrate-producing anaerobic genus Faecalibacterium ≥ 0.15% was protective against AAD, whereas abundance of Pseudomonas at baseline ≥ 0.75% (adjusted OR: 5.70; 95% CI: 1.70-19.06; P: 0.005) and Enterococcus at baseline ≥ 2.1% (adjusted OR: 7.16; 95% CI: 2.12-24.25; P: 0.002) were independent risk factors. CONCLUSIONS: Development of AAD in patients with sepsis is associated with dysbiosis before the start of antimicrobial treatment.