Procalcitonin-guided early cessation of antibiotics prevents gut inflammation and preserves gut microbiome: Data from the PROGRESS controlled trial.

The PROGRESS randomised trial (ClinicalTrials.gov: NCT03333304) showed that early stopof antibiotics guided by procalcitonin (PCT) decreased the incidence of infections by multidrug-resistant organisms and/or Clostridioides difficile and was associated with survival benefit. This study was conducted to investigate whether this survival benefit is associated with microbiome dysbiosis. Patients with sepsis due to lung infection, acute pyelonephritis or primary bacteraemia were randomised to standard-of-care (SoC) duration of antibiotics or early stop using PCT. Faecal samples were collected before, and 7 and 28 days after randomisation and analysed using 16S rRNA Nanopore sequencing. Calprotectin was measured using an enzyme immunoassay. Median (Q1-Q3) antimicrobial duration was 5 (5-7.5) days in the PCT arm and 11 (8-15) days in the SoC arm (P < 0.001). Faecal calprotectin levels were similar in the two treatment arms at baseline. By day 7, the levels of faecal calprotectin were significantly increased in the SoC arm (P = 0.002) but were unchanged in the PCT arm. Microbiome α- and β-diversity was similar at baseline in the PCT (n=81) and SoC (n=76) treatment arms. Shannon's index was significantly lower in the SoC arm on day 7 compared with baseline (median [Q1-Q3], 2.88 [2.37-3.39] at day 1 vs. 2.24 [1.52-3.08] at day 7; Pt-test = 0.0013). This was not the case for the PCT arm (median [Q1-Q3], 2.73 [2.26-3.4] at day 1 vs. 2.43 [1.81-3.21] at day 7; Pt-test = 0.037, Bonferroni corrected α = 0.0125). The relative abundance of Actinomycetota and Pseudomonadota was decreased in the PCT arm by day 7 and that of Bacillota was increased. Early PCT-guided stop of antibiotics contributes to decreased microbiome dysbiosis by day 7.