Pivmecillinam in the treatment of urinary tract infections caused by ESBL-producing bacteria - a randomized study

Antibiotic resistance is a major threat to public health causing treatment failure and complications for the patients and higher costs for health care.

The situation is particularly worrisome in gram-negative bacteria such as Escherichia coli – the predominant pathogen in urinary tract infections (UTI), and one of the leading causes of sepsis. Multidrug-resistant E. coli producing extended-spectrum beta-lactamases (ESBLs) are increasingly prevalent worldwide.

In many cases, evidence-based oral therapy is lacking.

Research evaluating oral treatments for febrile UTI caused by ESBL-producing bacteria has been ranked high priority in a recent systematic review and in a national expert consensus.

Specifically, finding alternatives to the intravenously administered broad-spectrum carbapenems, associated with high risks of collateral damage in the microbiota and resistance development, is urgently needed.

In the planned randomized controlled trial, we will evaluate the efficacy and safety of a narrow-spectrum penicillin, pivmecillinam, for febrile UTI caused by ESBL-producing E. coli.

In the 1-year project, coordinated from Uppsala University, we will establish the study protocol in national and international collaboration, assess the feasibility of the study, and submit applications to ethics and medical products authorities.

If non-inferiority is found, we expect the results will have an immediate impact on treatment guidelines that will benefit future patients and health care.