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

The randomized PROGRESS trial (ClinicalTrials.gov NCT03333304) proved that early stop of antibiotics in sepsis guided by procalcitonin (PCT) changes leads, among others, to decrease of the incidence of antibiotic-associated diarrhea (AAD) and preservation of gut microbiome diversity. We aimed to explore an association of AAD with baseline microbiome composition. Patients with sepsis were followed-up for 28 days for AAD development. As PCT guidance led to decrease of AAD, only patients of the comparator arm, i.e. under treatment with standard-of-care (SoC) duration of antimicrobials, were considered for this exploratory analysis. In case of diarrhea, Clostridioides difficile infection was thoroughly investigated and excluded. Fecal samples were collected before initiation of antimicrobials and microbiome analysis was done by 16S rRNA Nanopore sequencing. Shannon diversity index was similar at baseline in 31 AAD (3.01; Q1-Q3, 2.49-3.49) and 54 non-AAD (2.83; Q1-Q3, 2.16-3.27; p: 0.456) patients. Relative abundance of Bacillota was lower (p: 0.038) and of Pseudomonadota higher (p: 0.019) in AAD patients. Abundance of the butyrate-producing anaerobic genus Faecalibacterium ≥ 0.15% was protective against AAD whereas abundance of Pseudomonas at baseline ≥ 0.75% (ORadj, 5.70; 95% CI, 1.70-19.06; p: 0.005) and Enterococcus at baseline ≥ 2.1% (ORadj, 7.16; 95% CI, 2.12-24.25; p: 0.002), were independent risk factors. Development of AAD in sepsis patients is associated with dysbiosis before start of antimicrobial treatment.