Impact of selective digestive decontamination on the pangenome composition of ESBL-E. coli

In Dutch ICUs patients receive selective digestive decontamination (SDD) as a prophylactic antimicrobial treatment to prevent colonisation with potentially pathogenic microorganisms and subsequent infections, with a beneficial effect on 28-day mortality. In the R-GNOSIS ICU study, conducted outside of The Netherlands, SDD consisted of a mix of an oropharyngeal paste and a gastric suspension containing colistin, tobramycin and nystatin. These topical antimicrobial agents aim to target aerobic Gram-negative bacteria, S. aureus and yeast. SDD improves patient outcome, but its effects on the resistome and pangenome of potentially pathongenic microorganisms have not been extensively studied. In this work, we compared 129 genomes of E. coli isolates from patients that received SDD and patients that did not receive SDD, but standard care only (baseline patients) in five ICUs located across three European countries (R-GNOSIS ICU study). We found that the overall pangenome compositions of E. coli recovered from both patient groups were highly similar. Variations in the accessory genome were strongly associated with the phylogeny of isolates but not with the use of SDD. Similarly, the plasmidome variations were not explained by treatment, but rather by the interaction between ICU location and phylogroup. One antibiotic resistance gene, which confers resistance to tobramycin, was found to be more prevalent in SDD patients. This gene was flanked by IS26 elements and significantly co-occurred with blaCTX-M-15 in various plasmid backbones and chromosomal contexts. Notably, no mcr genes coding for colistin resistance were detected.