Characterization of ESBL/pAmpC-producing Escherichia coli isolates from long-term recurrent bloodstream infections using whole genome data and an in vivo mouse infection model

The aim of the current study was to investigate the rate of recurrent infections within individual patients caused by Extended-spectrum beta-lactamase and plasmid-AmpC-producing Escherichia coli (ESBL/pAmpC Ec) isolates, with more than one year interval. Thirty-one ESBL/pAmpC Ec isolates from 15 unrelated patients were collected from January 2014 through June 2017. The isolates were whole genome sequenced and analyzed for resistance genes, virulence genes and MLST. The isolates were further typed by cgMLST and CH-typing. Ten of the 15 patients experiencing recurrent infections were found to be infected a second or a third time with a highly similar strain, presumably as a relapsed infection with their own strain. The resistance and virulence properties of the strains were similar within individual patients, however quite diverse when comparing between patients. Strains suspected to cause relapsed infections were further studied in a murine peritonitis model. Representative strains from seven of the patients were able to cause infection in the mouse model, while the remaining three showed low virulence capability in the peritonitis mouse model. Relapsed bloodstream infections with ESBL/pAmpC Ec of closely related strains, occurring in the same patient with more than 12 month intervals, might be related to the previous episode and to less extend be caused by reinfection from a common source. From our analysis, strains able to cause such relapsed infection were relatively diverse between patients. Knowledge about host and strain factors influencing such recurring infections is needed to implement preventive measures.