Methenamine hippurate to prevent recurrent urinary tract infections in older women: protocol for a randomised, placebo-controlled trial (ImpresU).

INTRODUCTION: Methenamine hippurate is a urinary antiseptic used as preventive treatment for recurrent urinary tract infections (UTIs) in some Scandinavian countries. However, the scientific evidence for the preventive effect and safety for longer-term use is limited. The aim of this study is to assess whether methenamine hippurate can reduce the incidence of UTIs in older women with recurrent UTIs. METHODS AND ANALYSIS: The ImpresU consortium is a collaboration between Norway, Sweden, Poland and the Netherlands. The study is a randomised, controlled, triple-blind phase IV clinical trial. Women ≥70 years with recurrent UTIs are screened for eligibility in a general practice setting. We aim to include 400 women in total, with 100 recruited from each collaborating country. The participants are randomised to treatment with methenamine hippurate 1 g or placebo tablets two times per day for a treatment period of 6 months, followed by a drug-free follow-up period of 6 months. The primary outcome is number of antibiotic treatments for UTIs during the treatment period. The secondary outcomes include number of antibiotic treatments for UTIs during the follow-up period and self-reported symptom of severity and duration of UTI episodes. Differences in complications between the treatment groups are measured as safety outcomes. We also aim to investigate whether strain characteristics or phylogenetic subgroups of Escherichia coli present in the urine culture at inclusion have a modifying effect on the outcomes. ETHICS AND DISSEMINATION: Ethical approvals are obtained in all participating countries. The results will be communicated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04077580); EudraCT: 2018-002235-15.

Decisions on antibiotic prescribing for suspected urinary tract infections in frail older adults: a qualitative study in four European countries.

BACKGROUND: a suspected urinary tract infection (UTI) is the most common reason to prescribe antibiotics in a frail older patient. Frequently, antibiotics are prescribed unnecessarily. To increase appropriate antibiotic use for UTIs through antibiotic stewardship interventions, we need to thoroughly understand the factors that contribute to these prescribing decisions. OBJECTIVES: (1) to obtain insight into factors contributing to antibiotic prescribing for suspected UTIs in frail older adults. (2) To develop an overarching model integrating these factors to guide the development of antibiotic stewardship interventions for UTIs in frail older adults. METHODS: we conducted an exploratory qualitative study with 61 semi-structured interviews in older adult care settings in Poland, the Netherlands, Norway and Sweden. We interviewed physicians, nursing staff, patients and informal caregivers. RESULTS: participants described a chain of decisions by patients, caregivers and/or nursing staff preceding the ultimate decision to prescribe antibiotics by the physician. We identified five themes of influence: (1) the clinical situation and its complexity within the frail older patient, (2) diagnostic factors, such as asymptomatic bacteriuria, (3) knowledge (gaps) and attitude, (4) communication: interprofessional, and with patients and relatives and (5) context and organisation of care, including factors such as availability of antibiotics (over the counter), antibiotic stewardship efforts and factors concerning out-of-hours care. CONCLUSIONS: decision-making on suspected UTIs in frail older adults is a complex, multifactorial process. Due to the diverse international setting and stakeholder variety, we were able to provide a comprehensive overview of factors to guide the development of antibiotic stewardship interventions.

Multifaceted antibiotic stewardship intervention using a participatory-action-research approach to improve antibiotic prescribing for urinary tract infections in frail elderly (ImpresU): study protocol for a European qualitative study followed by a pragmatic cluster randomised controlled trial.

INTRODUCTION: Almost 60% of antibiotics in frail elderly are prescribed for alleged urinary tract infections (UTIs). A substantial part of this comprises prescriptions in case of non-specific symptoms or asymptomatic bacteriuria, for which the latest guidelines promote restrictiveness with antibiotics. We aim to reduce inappropriate antibiotic use for UTIs through an antibiotic stewardship intervention (ASI) that encourages to prescribe according to these guidelines. To develop an effective ASI, we first need a better understanding of the complex decision-making process concerning suspected UTIs in frail elderly. Moreover, the implementation approach requires tailoring to the heterogeneous elderly care setting. METHODS AND ANALYSIS: First, we conduct a qualitative study to explore factors contributing to antibiotic prescribing for UTIs in frail elderly, using semi-structured interviews with general practitioners, nursing staff, patients and informal caregivers. Next, we perform a pragmatic cluster randomised controlled trial in elderly care organisations. A multifaceted ASI is implemented in the intervention group; the control group receives care as usual. The ASI is centred around a decision tool that promotes restrictive antibiotic use, supported by a toolbox with educational materials. For the implementation, we use a modified participatory-action-research approach, guided by the results of the qualitative study. The primary outcome is the number of antibiotic prescriptions for suspected UTIs. We aim to recruit 34 clusters with in total 680 frail elderly residents ≥70 years. Data collection takes place during a 5-month baseline period and a 7-month follow-up period. Finally, we perform a process evaluation. The study has been delayed for 6 months due to COVID-19 and is expected to end in July 2021. ETHICS AND DISSEMINATION: Ethical approvals and/or waivers were obtained from the ethical committees in Poland, the Netherlands, Norway and Sweden. The results will be disseminated through publication in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT03970356.

Bacteriuria and vitamin D deficiency: a cross sectional study of 385 nursing home residents.

BACKGROUND: Up to half of elderly people at nursing homes have asymptomatic bacteriuria, and concentrations of 25-hydroxyvitamin D (25OHD) are generally low. Vitamin D is a modulator of the immune system and involved in protection of the epithelium in the urinary tract as well. The objective was to determine a possible association between bacteriuria and vitamin D deficiency among elderly people at nursing homes. METHODS: Cross-sectional study: Voided urine specimens and blood samples for cultivation and analysis of 25OHD were collected from elderly people at nursing homes in Sweden. Exclusion criteria were: urinary catheter, ongoing antibiotic treatment, incontinence or dementia too severe to provide a voided urine specimen or leave a blood sample, unwillingness to participate or terminal illness. Urine cultures and serum 25OHD concentrations were outcome measures and the association of bacteriuria with vitamin D deficiency was determined by logistic regression. RESULTS: Twenty-two nursing homes participated and 385 of 901elderly people provided voided urine specimens and blood samples. The mean age was 87 (SD 6.7), 69% women, 19% received vitamin D supplement, 13% had diabetes mellitus, and 54% were diagnosed with dementia. There was significant growth of potentially pathogenic bacteria in 32% (123/385) of voided urine specimens. Escherichia coli were present in 83% of positive urine cultures. The mean concentration of 25OHD in serum was 35 nmol/L (SD 21). Thirty-seven per cent (143/385) had 25OHD < 25 nmol/L, and 3.1% (12/385) 25OHD < 12.5 nmol/L. No association between bacteriuria and 25OHD < 25 nmol/L, OR 1.4 (0.86-2.3; p = 0.18) adjusted for age, gender, diabetes mellitus and dementia was found. However, if using 25OHD < 12.5 nmol/L as a cut-off for vitamin D deficiency the adjusted odds-ratio was 4.4 (1.1-17; p = 0.031). CONCLUSIONS: Bacteriuria and vitamin D deficiency was common. No association between bacteriuria and 25OHD < 25 nmol/L was found. If using 25OHD < 12.5 nmol/L as cut-off for vitamin D deficiency there was an association. However, this has to be interpreted with caution as causality cannot be evaluated as well as only few residents had 25OHD < 12.5 nmol/L.