It is estimated that resistance against antibiotics will result in 10 million deaths every year by 2050, followed by a reduction in Gross Domestic Product (GDP) ranging between 2% and 3.5%. The threat of antibiotic resistance is listed by the World Health Organization among the five top factors with impact on world health and economy. Extended-spectrum cephalosporins rank among the most frequently prescribed antibiotics for serious human bacterial infections. However, their excessive use in human and veterinary medicine resulted in a global increase of bacteria resistant to these antibiotics among humans but also livestock and companion animals. Typical for these bacteria is that they can transfer resistance to cephalosporins to other bacteria. As a result there are no limitations to their potential to spread. In addition to their transmission from human-to-human, the transmission of bacteria resistant to extended-spectrum cephalosporins or their DNA from animals-to-humans and vice versa has been strongly suggested. As a consequence, the collection of data regarding the relatedness of these bacteria or DNA of human and animal origin, as well as the assessment of their cross-transmission are essential for proposing interventions to resolve this well-acknowledged health threat. The studies presented in this thesis provide insights on emerging trends among bacteria resistant to extended-spectrum cephalosporins of human and animal origin, their cross-transmission within and between humans and animals, as well as the complexity of their epidemiology in order to assess the role of animals as a relevant source of such resistant bacteria for humans.