Optimizing treatment in men with urinary tract infection: a retrospective cohort study based on linked routine care data from general practice, microbiological laboratory and hospital

Background and relevance

Urinary tract infections (UTIs) without signs of tissue invasion (afebrile UTI (a-UTI)) in men are common in general practice but the scientific evidence for the best treatment is scarce. The NHG (Dutch College of General Practitioners (GPs)) UTI guideline recommends nitrofurantoin 100mg SR twice daily for 7 days as first-line treatment, and always ordering a urine culture in parallel. This is not based on clinical evidence but on expert consensus only. Further evidence is needed to optimize management of this common condition, as was highlighted in the Dutch Research Agenda for General Practice.

Problem definition and objectives

Recent observational studies have shown nitrofurantoin failure in 25-30% of a-UTI episodes in men. This could lead to potentially preventable morbidity, such as pyelonephritis and urosepsis, and mortality. Furthermore, it has been suggested that Dutch GPs perform a urine culture in only 40% of cases. Whether this deviation from recommended practice leads to worse patient outcomes is currently unknown.

Our objectives are therefore, in men with a-UTI, to:

• 1.1 Determine the percentage for whom a urine culture is ordered as well as the variation between GP practices;
• 1.2 Compare patient characteristics between those for whom a urine culture was and was not ordered;
• 1.3 Compare the therapy failure percentages, including type of failure (persisting symptoms, complications (e.g. pyelonephritis) without hospitalization, and complications (e.g. urosepsis) with hospitalization), of nitrofurantoin and other individual antibiotics between those for whom a urine culture was and was not ordered;
• 1.4 Identify predictors of treatment success of nitrofurantoin such as age, co-morbidity, sensitivity of causative uropathogen, recent hospitalization and recent outpatient visit to urology.

Among men with a-UTI for whom a urine culture was ordered to:

• 2.1 Determine the age-specific microbiological urine profile (presence of uropathogens and antibiotic resistance pattern);
• 2.2 Assess how frequent urine culture results lead to adjustment of the antibiotic treatment regimen;
• 2.3 Determine the rate of therapy failure of nitrofurantoin and other antibiotics in relation to the detected uropathogens and their resistance profiles.

Using the results of our analysis results, information in the published literature and expert input, we finally aim to:

• 3. Explore the potential cost-effectiveness of culturing urine from men with a-UTI routinely.

Research design

Retrospective cohort study using linked routine care data. Pseudonymized data on a-UWI in men from general practices in the Utrecht region (Julius Huisartsen Netwerk database; 2018-2022) will be linked by a Trusted Third Party to urine culture data from the regional diagnostic laboratory (Saltro/Unilabs) and data on outpatient visits and hospitalizations (Dutch Hospital Data). Study population Men (≥18 years) with GP-diagnosed a-UTI (ICPC codes U01 (dysuria), U02 (frequent micturition) or U71 (cystitis)) and relevant antibiotic prescriptions. Treatment failure will be defined as a new antibiotic prescription for persistence or worsening of symptoms or acute referral to urology or internal medicine >1 day and ≤30 days after the first antibiotic prescription for the a-UTI episode.

Intervention

As this is an observational cohort study no interventions will be performed.

Intended results

With randomised controlled trial evidence unlikely to become available in the coming years, our study will provide pivotal real-world evidence to inform the management of a-UTI in men, both in terms of treatment decisions and the potential for cost-effectiveness of routine urine culturing.

Impact

Current guideline recommendations for men with a-UTI are consensus based due to a paucity of supporting evidence. Our project will generate key knowledge about the most optimal management decisions in men with a-UTI and therefore inform future guideline development.