Yes / Antimicrobial resistance (AMR) is a growing global crisis with an increasing number of untreatable or exceedingly difficult-to-treat bacterial infections, due to their growing resistance to existing drugs. It is predicted that AMR will be the leading cause of death by 2050. In addition to ongoing efforts on preventive strategies and infection control, there is ongoing research towards the development of novel vaccines, antimicrobial agents, and optimised diagnostic practices to address AMR. However, developing new therapeutic agents and medicines can be a lengthy process. Therefore, there is a parallel ongoing worldwide effort to develop materials for optimised drug delivery to improve efficacy and minimise AMR. Examples of such materials include functionalisation of surfaces so that they can become self-disinfecting or non-fouling, and the development of nanoparticles with promising antimicrobial properties attributed to their ability to damage numerous essential components of pathogens. A relatively new class of materials, metal-organic frameworks (MOFs), is also being investigated for their ability to act as carriers of antimicrobial agents, because of their ultrahigh porosity and modular structures, which can be engineered to control the delivery mechanism of loaded drugs. Biodegradable polymers have also been found to show promising applications as antimicrobial carriers; and, recently, several studies have been reported on delivery of antimicrobial drugs using composites of MOF and biodegradable polymers. This review article reflects on MOFs and polymer-MOF composites, as carriers and delivery agents of antimicrobial drugs, that have been studied recently, and provides an overview of the state of the art in this highly topical area of research.

The environment is increasingly recognised as a key player in the emergence and mobilisation of antibiotic resistance, which negatively impacts human health, healthcare systems, and farming practices worldwide. Recent work has demonstrated concentrations of antibiotics in the natural environment may select for resistance in situ, but a scarcity of meaningful data has prevented rigorous environmental risk assessment of antibiotics. Without such data, mitigation strategies, such as improved antibiotic stewardship or environmental discharge limits, cannot be effectively designed or implemented. This thesis designed and developed two methods for determining effect concentrations of antibiotics in complex microbial communities, thereby generating a significant amount of data to address this knowledge gap. Minimal selective concentrations (MSCs) were determined in long term selection experiments for four classes of antibiotic at concentrations as low as 0.4 μg/L, which is below many measured environmental concentrations. Lowest observed effect concentrations were determined using a short term, growth based assay which were highly predictive of MSCs. A novel finding was significant selection for cefotaxime resistance occurred at a wide range of antibiotic concentrations, from 125 μg/L - 64 mg/L, which has important clinical implications. Determination of MSC in single species assays was also shown to be a poor predictor of MSC in a complex microbial community. Co-selection for antimicrobial resistance was demonstrated in selection experiments and through improved understanding of class 1 integron evolution, assessing selective effects on resistance gene acquisition using a novel PCR method and next-generation sequencing. In the final study, a novel resistance determinant (UDP-galactose 4-epimerase) conferring cross-resistance to biocides and antibiotics was discovered, providing a target for further study. These findings indicate selection and co-selection for antimicrobial resistance is likely to occur in the environment, and provides the means to rapidly generate further data to aid in the development of appropriate mitigation strategies.

Aim: This thesis aims to explore and investigate the level and process of adoption of Antimicrobial Stewardship Programmes (ASPs) and factors influencing their implementation in Saudi Ministry of Health (MOH) hospitals. The findings of this study will provide hospitals and policy makers with evidence-based recommendations on how barriers to ASPs adoption can be overcome, which will ultimately improve antimicrobial use and reduce antimicrobial resistance (AMR). Method: A mixed method approach was carried out using both qualitative and quantitative research methods. Semi-structured interviews were conducted with healthcare professionals in three Saudi hospitals to explore the enablers and barriers to their adoption of ASPs. A survey was then developed based on these findings to investigate the level of hospitals' adoption of ASPs and factors influencing their implementation at a national level. Further, a case study using in-depth interviews was utilised to understand the process of ASP adoption in a Saudi hospital, and how adoption challenges were addressed. Finally, a self-administered questionnaire was used to examine patients' knowledge and perceptions of antimicrobial use and resistance, and to evaluate the institutional role of patient education on antimicrobial use in two Saudi hospitals. The overall methodology of the research is summarised in Figure I. Results: Despite the introduction of a national ASP strategy, adoption of ASPs in Saudi MOH hospitals remains low. Organisational barriers such as the lack of senior management support, lack of supportive IT infrastructure and the shortage of ASP team members hinder hospitals' efforts to adopt ASPs. Further barriers relate to the lack of formal enforcement by MOH and the physicians fears of patients' complications and clinical liability. Patients admitted to Saudi hospitals lack knowledge and perceptions of AMR, and the adoption of ASPs may improve hospitals' role in patients' education. Conclusions: Despite the established benefits of ASPs, their adoption in Saudi MOH hospitals remains low. Urgent action is needed to address the strategies priorities associated with AMR, including access to antimicrobials, antimicrobial stewardship and education and research. Policy makers are urged to consider making ASPs adoption in hospitals a regulatory requirement supported by national guidelines and surveillance programmes. It is essential to increase the provision of ID and infection control residency and training programmes to meet the extreme shortage of ID physicians, pharmacists, microbiologists and infection control practitioners. Higher education institutions and teaching hospitals are required to introduce antimicrobial prescribing and stewardship competencies into undergraduate Medical, Pharmacy, Dental, Nursing and Veterinary curriculum, as well as introduction of AMR topics in order to increase knowledge and awareness of ASPs and AMR. Collaboration between ASPs adopting and non-adopting hospitals is essential to share implementation experience, strategies and solutions to overcome barriers. Healthcare specialised associations are needed to be part of AMR conversation and guide healthcare professionals' training and accreditation. Multiple stakeholders should be actively part of the conversations around tacking AMR. Primary care, secondary care, community pharmacies and policy makers should strive to create a shared culture of responsibility among all healthcare partners to improve antimicrobial therapy and reduce risks of AMR.