Epidemiology of extended-spectrum β-lactamase-producing Escherichia coli

Abstract: Extended-Spectrum β-Lactamase and plasmid mediated AmpC (ESBL/pAmpC)-producing Escherichia coli (E. coli) has during the last decades emerged worldwide and is now an increasing problem in both human and animal health. In order to slow down the spread it is important to study success factors and transmission routes so that preventive measures can be efficient. In paper I we studied what sectors that contribute to human carriage and human clinical infections by investigating the molecular epidemiology of ESBL/pAmpC-producing E. coli in leafy greens, meats, farm animals, human community carriers and human blood stream infections. We found that different ESBL/pAmpC-genes, plasmids and E. coli MLST lineages dominated in isolates from humans compared to isolates in farm animals, foods and meats, but some traits overlapped. All in all, we concluded that a very small proportion of human bloodstream infections with ESBL/pAmpC-producing E. coli could have originated from the foods we consume. To better understand the prevalence of ESBL/pAmpC-producing E. coli in the community we performed two carrier studies described in papers II and III. In paper II we found that 4.7% of the Swedish population carried ESBL/pAmpC-producing E. coli in their intestine. Risk factors associated with carriage was travel to countries in Asia and Africa and a diet that did not include pork. In paper II we also explored which E. coli populations that accumulated in clinical infections compared to carriers and found that the ESBL-gene blaCTX-M-15 and E. coli ST131 and its subclone H30-Rx/C2 were overrepresented in bloodstream infections. In paper III we joined forces with our neighbouring countries around the Baltic Sea, Finland, Latvia, Russia, Poland and Germany to investigate the prevalence of ESBL-producing E. coli and K. pneumoniae in specific populations in all participating countries. We found large differences in prevalence between countries with the highest in Russia (23.4%) and the lowest in Latvia (1.6%). No carbapenemase producing isolates were identified in any of the investigated countries. In paper II E. coli ST131 was identified as the most common ST to cause bloodstream infections in Swedish patients. This lineage is internationally wide-spread and commonly cause severe infections. In paper IV we explored the Swedish epidemiology of this highly pathogenic ESBL-producing E. coli lineage by conducting a phylogenetic comparison between Swedish and international isolates. We found, in accordance with our hypothesis, that several introductions from the international lineage have shaped the Swedish ST131 population. Tight genetic relationships between isolates in clonal clusters makes it difficult to perform outbreak investigations with ST131. In addition, we identified highly conserved plasmids in all clusters with Swedish isolates even though they had been separated for several years indicating a strong co-evolution of plasmids in some ST131 lineages. Taken together our studies show that although there is a high prevalence of ESBL/pAmpC-producing E. coli, particularly in poultry and chicken meat products, the major source for ESBL/pAmpC producing E. coli causing human infections is humans to human transmission. Although we do not see a great contribution from the animal and food sector in Sweden it could change in the future if an epidemiological shift to more human pathogenic strains take place in e.g. poultry. This is why a multi-sectorial approach to reduce the levels of ESBL/pAmpC-producing E. coli in all sectors is needed. Of particular interest is the highly pathogenic E. coli lineage ST131 that is responsible for a large proportion of infection with ESBL/pAmpC-producing E. coli. Carriers of ST131 could therefore be at greater risk of getting an infection and there might be incentive for considering them as high risk carriers. The high clinical relevance of ESBL-producing E. coli ST131 prompts further monitoring since this lineage has large potential to accumulate resistance to last resort drugs such as carbapenems and colistin.