Pivmecillinam for febrile UTI – a randomized controlled trial

Bacterial infections are the second-leading cause of death worldwide, and urinary tract infection (UTI) is the second most common infection with more than 150 million cases every year. Escherichia coli is the predominant pathogen in UTI, and the most common cause of bloodstream infections. E. coli is also the leading cause of death attributable to antibiotic resistance with > 250,000 deaths per year.

Treatment of febrile UTI (fUTI), i.e.

UTI with systemic infection and fever, is becoming increasingly challenging due to the increasing prevalence of resistant bacteria and the lack of new oral antibiotics.

Resistance rates in E. coli against the first-line oral treatment ciprofloxacin are already 13.8% in Sweden and 25-40% in Southern Europe. Therefore, there is an urgent need to investigate if existing old antibiotics can be repurposed and used for fUTI.

We propose the first randomized controlled trial to evaluate the efficacy of a narrow-spectrum penicillin, orally administered pivmecillinam, for E. coli fUTI versus standard of care.

Pivmecillinam has high activity against E. coli (>95%) and is associated with a lower risk of side effects and resistance development compared to the current standard treatments. The study will be conducted at hospitals in Sweden, Norway and Denmark. If non-inferiority is shown, pivmecillinam will be a much-needed addition to the sparse therapeutic arsenal for fUTI.

The results might have an immediate impact on treatment practice and guidelines.