ESBL - Producing Escherichia coli : Antibiotic Selection , Risk Factors and Population Structure

Urinary tract infection (UTI) is one the most common bacterial infections and is regularly treated in primary health care. The most common cause of UTI is extraintestinal pathogenic Escherichia coli (ExPEC) already present in the intestinal microflora, often as the dominating strain. Resistance in E.coli is increasing and especially isolates producing Extended-Spectrum Beta-Lactamases (ESBL) have been reported worldwide. Treatment of UTI is usually initiated by the general practitioners and a significant proportion of clinical isolates are now resistant to first line antibiotics. The global dissemination of resistant E.coli has in particular been driven by the spread of a few specific E.coli-lineages and it seems that there is a difference between the sequence types found among resistant E.coli, ESBL-producing E.coli and antibiotic susceptible E.coli. The overall objectives of this thesis were to investigate (i) antibiotics involved in selection of ESBL-producing E.coli, in an experimental mouse model in vivo, (ii) risk factors for UTI with ESBL-producing E.coli and (iii) to describe the phylogenetic composition of E.coli populations with different resistance patterns. We found that different antibiotics can select for the ESBL-producing E.coli, even anti-Grampositive antibiotics as dicloxacillin and clindamycin showed selective abilities. While dicloxacillin has no effect on anaerobic Gram-negatives, this is the case for clindamycin. The selective abilities of other beta-lactam antibiotics varied, with selection identified by cefotaxime, cefuroxime and penicillin. The triple-case control study showed that exposure to antibiotics is not a good predictor for risk of UTI with ESBL-producing E.coli. There were few differences between the case groups when compared to the uninfected group. However, when case groups where compared to each other, healthcare association and hospital admission proved to be independent risk factors for UTI with ESBL-producing E.coli. When typing uropathogenic E.coli, we less frequently saw ST131 among non-ESBL than among ESBL-producing E.coli. We found that ESBL-producing E.coli, resistant E.coli and susceptible E.coli in turn were dominated by different MLVA codes and sequence types. Overall the susceptible E.coli was a much more diverse group, whereas resistant and ESBL-producing E.coli were found in larger clusters, indicating that the success of resistant lineages like O25b-ST131 is mainly due to positive selection of previously specialized UPEC with newly gained resistance.