Antibiotic resistance gone wild : A One Health perspective on carriage, selection and transmission of Extended-Spectrum Cephalosporinase- and Carbapenemase-producing Enterobacteriaceae

Abstract: Antibiotics have saved millions of lives since they came into clinical use during the Second World War in the 1940s. Today, our effective use of antibiotics is under great threat due to emerging antibiotic resistance in bacteria. This thesis addresses the problems of antibiotic resistance from a ”One Health” perspective. The focus is on antibiotic resistant Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) in the environment and wildlife, and also considering the situation in healthy humans and livestock. In Paper I-III, high occurrence of Extended-Spectrum Beta-Lactamase (ESBL) -producing E. coli and/or K. pneumoniae was detected in fecal samples from wild birds, and the bacteria had genetic similarities to bacteria that cause disease in humans. Proximity to humans was associated with higher occurrence of cephalosporinase (ESBL and pAmpC)-producing E. coli in wild gulls. In Paper IV, ciprofloxacin resistant E. coli was enriched in the gut of mallards exposed to low concentrations of ciprofloxacin, and plasmid conjugation between E. coli bacteria readily took place. In Paper V, carbapenem resistant and blaOXA-48 harbouring- E. coli/K. pneumoniae was rare, but present in healthy humans in rural Cambodia, while cephalosporinase-producing E. coli/K. pneumoniae was common in both humans and livestock. The same ESBL/pAmpC genes were detected in humans and livestock, and exposure to animal manure and slaughter products were risk factors for fecal carriage in humans.In conclusion, wild birds can function as potential resistance reservoirs and sentinels for antibiotic resistant E. coli. Environmental pollution from humans is the primary source for antibiotic resistant Enterobacteriaceae found in wildlife, but selection for antibiotic resistant bacteria may also occur in wild birds. The results indicate that transmission of cephalosporinase-producing E. coli/K. pneumoniae occur between wildlife, humans and livestock, but more in-depth molecular work is needed to determine the mechanisms of dissemination. The high community carriage of multidrug-resistant bacteria in rural Cambodia is worrying and highlights Southeast Asia as a hotspot for antibiotic resistance. Antibiotic resistance surveillance is biased towards high-income countries and research should be focused more on low- and middle-income countries, and also include the important “One Health” perspective.