Assessing antimicrobial resistance among uropathogens

UTIs are extremely common, affecting >400-million people worldwide annually. The burden of UTIs is increasing globally and is complicated by rising rates of antimicrobial resistance (AMR). UTIs are the most common infectious disease affecting our ageing population, and one of the most frequent healthcare-associated infections, particularly in patients with urinary catheters. Severe infections are a frequent cause of sepsis presentations to the Emergency Department. One in four women will have recurrent infections, representing a substantial global healthcare problem, with negative consequences for quality of life, mental health, socialising, engagement with work and daily activities, and sexual wellbeing. There is a clear and pressing need for the development of effective oral antibiotics for the treatment of uncomplicated urinary tract infections (UTIs) caused by multidrug-resistant (MDR) uropathogens. New oral agents, such as gepotidacin and tebipenem provide optimism for the future antibiotic armamentarium, but development of resistance proportional to their use remains a concern. Current recommended oral antibiotic for UTIs, such as nitrofurantoin, fosfomycin tromethamine, ciprofloxacin and amoxicillin-clavulanate, and pivmecillinam have limited urinary pharmacokinetic (PK) and pharmacodynamic (PD) data to inform UTI-specific susceptibility breakpoints and dosing schedules that correlate with clinical and microbiological outcomes. Our work examines how PK/PD investigations can advance the treatment options for patients with UTIs to provide a pathway for UTI drug development, inform susceptibility breakpoints, and optimise dosing schedules to prevent the emergence of resistance and preserve antibiotic activity for the future. Short term projects include the validation of direct antimicrobial susceptibility testing on urine samples and broth microdilution (BMD) antimicrobial susceptibility testing of urinary isolates collected into the UTI Isolate Repository. Longer term projects include assessing bacterial kill and emergence of resistance within a dynamic bladder infection in vitro model.