Egill Snaebjörnsson Arnljots

Rational use of antibiotics in urinary tract infections in adults

Antibiotic resistance is a serious and growing public health problem. It is essential that antibiotics are used properly. Elderly people are often prescribed antibiotics, sometimes on false grounds. Recurrent urinary tract infections contribute to the extensive use of antibiotics.

Nonspecific symptoms, without concomitant urinary tract symptoms, are often misinterpreted as urinary tract infections and contribute to a large number of antibiotic prescriptions, whereby interventions to reduce unnecessary use of antibiotics are very much needed. There is weak but insufficient scientific support for methenamine hippurate as a preventive treatment for recurrent urinary tract infections.

New treatment guidelines were introduced in 2013 for acute cystitis in men, switching to pivmecillinam or nitrofurantoin instead of quinolones. As this was done without a previous clinical trial, an analysis of complication frequency is very much needed.

Aim

To evaluate if changed guidelines for acute cystitis have resulted in failure of therapy, recurrence, and infection complications. To identify factors contributing to prescription of urinary tract antibiotics to the elderly and to develop and evaluate a multifaceted intervention to lower antibiotic use. To determine if methenamine hippurate is effective against recurrent urinary tract infections.

Paper I is a register study including men ≥ 18 years in the Västra Götaland region between December 2011 and January 2020. Regression analyses will be performed to determine connections between complications and choice of antibiotic in the primary infection.

Semi-structured interviews will be conducted in Paper II to investigate which factors influence decisions to prescribe urinary tract antibiotics to the elderly. Based on these results, a “toolbox” of aids and instruments will be developed to support optimization of antibiotic prescription.

In Paper III, nursing homes are randomized to the multifaceted antibiotic stewardship intervention from Paper II or to a control group. Evaluation will be based on diagnostics and antibiotic use in suspected urinary tract infection and follow-up of complications.

Paper IV is a triple-blind, randomized clinical trial of safety and efficacy in prophylactic treatment with methenamine hippurate in elderly women with recurrent urinary tract infections. A total of 400 women ≥ 70 years will be randomized to placebo or methenamine hippurate 1g x 2 for 6 months. Primary outcome variable: Number of treatments with urinary tract antibiotics day 2-180. Secondary outcome variables: Number of treatments with urinary tract antibiotics during six months after end of treatment, side effects and complications.

Paper I will illuminate the consequences of the therapy shift from quinolones to pivmecillinam/nitrofurantoin in the treatment of acute cystitis in men.

If the intervention from Paper II-III increases compliance with guidelines for the diagnosis and treatment of urinary tract infections in the elderly, implementation may lead to a more rational use of antibiotics.

Regardless of the outcome, the results of Paper IV will be important: if methenamine hippurate reduces the need for antibiotic usage in urinary tract infections, this will be of great importance. If, on the other hand, it has no effect, recommendations to refrain from using methenamine hippurate can be made.

University of Gothenburg
Main Supervisor Pär-Daniel Sundvall, MD, PhD