Abstract
Background: Third and fourth generation cephalosporins are listed by the World Health Organization as critically important antimicrobials, with the highest priority for human medicine. The main mechanism of resistance to third and fourth generation cephalosporins, also referred to as Extended Spectrum Cephalosporins (ESC), is degradation of the antimicrobial by enzymes.
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In species of Enterobacteriaceae, different families of Extended Spectrum Beta-Lactamases (ESBL) and plasmid-mediated AmpC beta-lactamases (pAmpC) are the most predominant enzymes. In poultry and poultry products, occurrence of ESBL/pAmpC in isolates of Escherichia coli and Salmonella enterica has been extensively described. Therefore, poultry has been suggested as a reservoir of ESBL/pAmpC-producing E. coli and Salmonella causing infections in humans. Data of ESBL/pAmpC-producing E. coli and Salmonella from poultry is scarce in Latin America. A research-driven initiative for integrated surveillance of Antimicrobial Resistance (AMR) was introduced in Colombian poultry production. Before this initiative, data on the status of AMR in agricultural settings was absent in the country. Aims of the research: The aims of the present thesis were i) to describe an initiative to develop an integrated program on AMR surveillance in Colombia; ii) to provide a highly-detailed characterization of ESBL/pAmpC genetic determinants in E. coli and S. enterica from poultry; iii) to reflect on the impact of poultry farming and commerce in the dissemination of ESBL/pAmpC. Results: The description of an initial consortium of stakeholders for the initiative of an integrated surveillance system in Colombia was provided (Chapter 2). From this initiative, baseline data of resistance to ESC was collected for Salmonella and E. coli. As a result, high level of similarity of ESBL/pAmpC genes and carrying plasmids was observed within E. coli (Chapter 3) and Salmonella (Chapter 4) in the country. Some gene-plasmid combinations were common between E. coli and Salmonella (e.g. blaCMY-2-IncI1 and blaSHV-12-IncI1) (Chapter 5). Overall, the combination of blaCMY-2 and IncI1/Sequence Type (ST) 12 plasmids was the most prevalent, and a high genomic relatedness was found among these plasmids within and between E. coli and Salmonella from Colombia and from other countries (Chapter 5). A marked geographical clustering within the most prevalent Salmonella serovar-STs in Colombia, S. Paratyphi B variant Java (here referred as S. Java) ST28 and S. Heidelberg ST15 was observed (Chapter 4). Subsequent analysis including S. Java ST28 genomes from other Latin American countries, showed high level of genomic relatedness across Latin American countries, indicating the circulation of a conserved clone of S. Java ST28 within the region (Chapter 6). Conclusions: In E. coli in poultry from Colombia and other countries, dissemination of ESBL/pAmpC is mainly mediated by transfer of genes and plasmids. In S. enterica from Colombia, dissemination is mainly mediated by clonal spread of genes, plasmids and strains combined. The dissemination within and between countries of poultry-associated ESBL/pAmpC can occur due to common practices of poultry farming and commerce. In order to measure the success of future interventions against AMR, it is necessary to implement integrated surveillance systems at national scale in Latin American countries.
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