Therapeutic strategies for multi-resistant Escherichia coli in urinary tract infections—a cause for concern

Abstract Antimicrobial resistance (AMR) is a serious and growing public health concern driven by multiple factors. Urinary tract infection (UTI) is one of the infections commonly associated with AMR, and more than 80% of UTIs are caused by Escherichia coli. MDR E. coli is a significant problem that requires urgent intervention, particularly in complicated UTIs (cUTIs) with underlying comorbidities. Although prevalence rates of MDR E. coli vary globally, it remains a critical clinical and economic challenge on every continent. The majority of MDR E. coli strains produce ESBLs, followed by AmpC enzymes, making them generally resistant to penicillins, cephalosporins and aztreonam. While there are some therapeutic options for uncomplicated UTIs (uUTIs), choices are limited for cUTIs, with carbapenems being the mainstay of treatment. However, carbapenem resistance is on the rise, severely impeding clinical regimens. With very few options available, combinations of antimicrobial agents for synergistic activity are increasingly relied upon for carbapenem-resistant E. coli. This situation has compelled the search for novel antimicrobial agents, which are slowly entering the market, although not as quickly as AMR is spreading worldwide. Current focus is shifting towards alternative antimicrobial therapies that exhibit broad-spectrum bactericidal activity and immunomodulatory effects, considered for both preventive and therapeutic strategies. A multi-disciplinary approach combining novel antimicrobials, innovative therapies and robust infection control measures will be essential to effectively manage MDR E. coli in uUTIs and cUTIs and mitigate the global threat of antibiotic resistance.