| Summary: | <p>Antibiotic resistance (AMR) presents a significant global threat, exacerbated by the extensive use of antibiotics in food-producing animals. To address this issue, there is an urgent need to identify effective alternatives to clinical antibiotics currently employed in livestock farming. Nitroxoline (8-hydroxy-5-nitroquinoline, NTX), an established antibiotic, primarily used for uncomplicated urinary tract infections (UTIs) in human, has emerged as a potential candidate for farm animal use due to its promising pharmacological properties and low toxicity. However, crucial data regarding its efficacy and safety in target animals appear to be very limited, hindering its comprehensive evaluation and optimisation for poultry production.</p>
<p>My thesis aims to evaluate NTX’s potential as an alternative antibiotic for farm animals, with a focus on broiler production. Firstly, a molecular epidemiology analysis of colistin resistance in Laos was initiated, applying a one-health sampling model (Chapter 3). This study confirmed the widespread occurrence of mobile colistin resistance (<em>mcr</em>) genes across human, animal, and the environmental sectors, with flies potentially involved in the dissemination of <em>mcr</em> genes, posing a potential risk to human health. Subsequent investigations focus on identifying and characterising NTX as a novel antibiotic for animal use.</p>
<p><em>In-vitro</em> experiments (Chapter 4) demonstrated the promising antibacterial activity of NTX against multiple animal bacterial pathogens, coupled with its low potential for selecting resistance. NTX-resistant mutants, when obtained, were unstable and posed a significant fitness cost. <em>In-vivo</em> evaluation (Chapter 5) established an optimal dosage regimen (100 mg/kg of NTX in feed) for treating <em>Salmonella</em> infections in poultry without promoting the development of resistance. Pharmacokinetic (PK) profiles in chicken plasma (Chapter 6) and drug residue clearance patterns of NTX in tissues (Chapter 7) were investigated using an established ultra-high performance liquid chromatography-MS/MS (UPLC-MS/MS) method, providing valuable insights into NTX's pharmacological properties, and thus, determining withdrawal times and ensuring drug-food safety-levels. Furthermore, understanding the effect of NTX on modulating the chicken gastrointestinal microbiota was determined by 16S rRNA sequencing analysis following NTX administration (Chapter 8) and clearly demonstrated its impact on microbial communities, guiding future antibiotic stewardship practices.</p>
<p>My studies and thesis underscore the potential of NTX as a viable alternative for bacterial infection prevention/treatment in poultry farming. The findings contribute to the development and prudent use of NTX in farm animal production, offering a promising solution to the challenge of AMR in agriculture.</p>
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