Shotgun metagenomics for microbiome and resistome detection in septic patients with urinary tract infection

In sepsis, early and appropriate antibiotic therapy is key but is frequently challenging due to the increasing incidence of multidrug-resistant bacteria. The feasibility of shotgun metagenomics (SM) has been scarcely assessed in urinary tract infections (UTIs). In this study, the feasibility of SM to detect both the microbiome and the resistome in patients with confirmed UTI-related sepsis was evaluated. Urine samples were obtained from 40 adult patients with UTI-related sepsis. Conventional culture was used as a reference. Following total DNA extraction and depletion of human DNA, SM was performed using Ion Proton^TM technology. Bioinformatics analysis was conducted using Geneious^Ⓡ software as well as online tools from the Center for Genomic Epidemiology. For the microbiome, SM was consistently concordant when urine culture was positive with only one bacterium (mainly Escherichia coli). For the resistome, results were in agreement with antimicrobial susceptibility testing with no major discrepancies. SM consistently identified bla_CTX-M genes responsible for resistance to third-generation cephalosporins. Resistance to aminoglycosides and fluoroquinolones was identified in all patients. This pilot study confirms that SM can provide clinically relevant information both on the microbiome and the resistome from urine samples of patients with UTI-related sepsis.