Recurrent infection with Extended-Spectrum Beta-Lactamase (ESBL) -producing Enterobacteriaceae

Abstract: Infections with Extended-Spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae (EPE) are increasing globally. The most common EPE are the gut pathogens Escherichia coli (ESBL-E. coli) and Klebsiella pneumoniae (ESBL-K. pneumoniae). The spread of antimicrobial resistance (AMR) in these organisms is due both to the spread of high-risk bacterial clones and to the transfer of AMR-genes via easily transmissible plasmids. This thesis focuses on factors of importance for recurrent EPE- infection. In paper I, the frequency of subsequent EPE-positive clinical cultures in an unselected patient group with a fecal screen or clinical culture positive for EPE was investigated. It was uncommon with a following clinical culture in patients with a positive fecal screen, but a new EPE-infection was common (almost 30%) in patients with a previous EPE-positive clinical culture (>90% urine cultures). In paper II, the rate of a change of species and possible ESBL-carrying plasmid transfer between clinical ESBL-E. coli and ESBL-K. pneumoniae isolates in subsequent infections was investigated by a novel plasmid typing technique, Optical DNA mapping (ODM). The rate of a change of species was shown to be low (<3%). Possible transfer of plasmids was found in a few cases. ODM in these cases rendered valuable information of plasmid numbers, plasmid sizes and the location of resistance genes. Paper III was a retrospective study of bacterial factors of importance for recurrent ESBL- E. coli UTI in 123 patients. Almost all isolates causing recurrences were of the same phylogroup as the index isolate. PFGE of a subset of isolates showed strain homology in 98%. Phylogroup B2 dominated, and within this phylogroup, presence of the subclone ST131- O25b-fimH30Rx was associated with multiple recurrences. In paper IV, ESBL-E. coli isolates from recurrent and sporadic UTI were prospectively collected. A comparison of bacterial characteristics with focus on ST131-O25b and its subclones showed an increase in risk of recurrence in patients infected with the virulent subclone. In conclusion, this thesis provides valuable new knowledge about factors influencing recurrences of EPE-infection.

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