Half of all urine infections in some UK communities no longer respond to first-line antibiotics, forcing GPs to prescribe stronger drugs that are themselves losing effectiveness. This programme tackles a dangerous cycle: when GPs switch antibiotics in response to rising resistance, the replacement drugs can also breed resistance, leaving fewer options. The research will run three staggered clinical trials across different NHS regions, each testing a tailored intervention—such as promoting pivmecillinam or fosfomycin—based on local resistance patterns. The team will combine national surveillance data with whole-genome sequencing of bacteria to understand how resistance spreads at the microbial level. If successful, the programme could shift antibiotic stewardship from a one-size-fits-all approach to a dynamic system where prescribing policy adapts to real-time local resistance data. That would mean fewer patients suffering prolonged, severe infections that require multiple courses of antibiotics. The results are expected to inform national antimicrobial policy, and the programme is designed so the NHS can continue the trials indefinitely after the grant ends.
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Research question The aim is to optimise UK antibiotic prescribing for urinary tract infections (UTIs) in primary care, in response to local antimicrobial resistance (AMR) trends. Background AMR is a serious threat to health. Unchecked, infections become untreatable with some experts predicting more AMR than cancer deaths by 2050. Urinary tract infection (UTI) is the most common bacterial infection treated by the NHS, mostly using antibiotics prescribed in primary care. In some patients, UTI AMR rates are as high as 50%, resulting in longer, more severe infections, requiring multiple antibiotic courses. The National Institute for Health and Care Excellence recommends nitrofurantoin or trimethoprim first-line. In recent years, GPs and nurses have been encouraged to prioritise nitrofurantoin over trimethoprim. Some studies suggest this has reduced trimethoprim AMR, but at the expense in some areas of increasing nitrofurantoin AMR, as well as increasing rates of co-amoxiclav and cephalexin. Although there are options, such as encouraging the use of pivmecillinam/ fosfomycin over trimethoprim/ nitrofurantoin) there is a lack of evidence to support decision making. Aims, objectives and methods This programme seeks to: (i) provide the evidence needed by policy makers; and (ii) deliver a step-change in antibiotic stewardship research by focussing primarily on AMR and not just antibiotic prescribing. The overall aim is to establish a virtuous cycle of common protocol , efficient design randomised controlled trials (RCTs) that provide evidence to inform antibiotic prescribing policy in response to local AMR challenges in community managed UTIs. We propose four integrated workstreams (WS). WS1 activities, occurring once, will: (i) use routine UK Health Security Agency (UKHSA) data to describe where AMR UTIs are most prevalent; (ii) select candidate Integrated Care Boards (ICBs) for intervention; and (iii) in line with MRC guidance, develop a behaviour change intervention that can be delivered at scale by ICB medicine optimisation/ antimicrobial stewardship teams. WS2, 3 and 4 will repeat within each RCT, conducted in a different ICB. WS2 will: (i) determine the AMR characteristics needed to inform RCT design; (ii) compare UKHSA AMR data with research laboratory AMR testing of urinary isolates from the selected ICB; (iii) identify microbial pre- and co-resistance, virulence and population structure using whole genome sequencing; and (iv) tailor the WS1 developed intervention to the needs of the selected ICB. WS3, the RCT internal pilot, will: (i) conduct a mixed methods process evaluation; (ii) evaluate intervention effects on antibiotic dispensing and patient safety; (iv) establish the feasibility of cost data collection and develop a health economics analysis plan; and (v) report results against stop/go criteria. WS4 will complete, analyse and report the RCT. Timelines for delivery A five-year programme: WS1 starting 1.7.2023. Each RCT (WS2, 3 and 4) lasts 36 months, staggered internal pilots starting 1.7.2024, 1.4.2025 and 1.1.2026. Final report submitted July 2028. Anticipated impact and dissemination Results expected to influence national antimicrobial policy. Outputs to include final report, publications, plain English and technical summaries. End of programme event to disseminate results and invite NIHR and UKHSA to subsume funding to perpetuate programme.
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