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Objectives: The aim of this study was to investigate the impact of age on the diagnostic properties of typical symptoms of urinary tract infection (UTI) in women presenting in general practice with symptoms suggestive of UTI with significant bacteriuria as the reference standard., Design: Diagnostic accuracy study., Setting: General practice, Copenhagen, Denmark., Participants: Adult 15 years or older. Women presenting in general practice with symptoms suggestive of UTI where urine was collected for investigation., Primary and Secondary Outcome Measures: Accuracy of four symptoms of UTI (dysuria, frequency, urge and abdominal pain) in six different age groups., Results: 90 practices included 1178 adult women. The prevalence of bacteriuria varied between 30% in women aged 30-44 years and 67% in women aged 75-89 years. The likelihood ratios for dysuria varied between age groups with the best performance in women aged 15-29 (positive likelihood ratio (pLR): 1.62 (1.30-1.94), negative likelihood ratio (nLR): 0.36 (0.19-0.54)) and women aged 30-44 (pLR: 1.74 (1.30-2.17), nLR: 0.48 (0.27-0.68)). CIs included or approximated one for the remaining symptoms in most age groups. When symptoms were combined to calculate post-test probabilities, the combined effect of the varying prevalence of bacteriuria and the varying diagnostic values resulted in a large variation of the post-test probabilities between age groups., Conclusions: The diagnostic value of symptoms of UTI as well as the prevalence of bacteriuria in women presenting to general practice with suspected UTI vary between age groups with considerable clinical implications. Diagnostic studies should take demographics such as age into consideration., Trial Registration Number: ClinicalTrials.gov: NCT02698332., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Urinary tract infection (UTI) is a common condition in general practice, and urine culture can help reduce inappropriate antibiotic prescriptions. In case of delay of the result, antibiotic treatment can be guided by one or more point-of-care (POC) tests. In Denmark, POC microscopy and POC urine culture are widely used for this purpose., Objectives: To investigate if availability of POC microscopy or POC culture in general practice was associated with a more appropriate treatment decision in patients with suspected UTI while waiting for the result from the microbiological laboratory., Methods: This prospective observational study was conducted in 2016 in general practice in the Copenhagen area, Denmark. Data on all patients presenting in general practice with symptoms of UTI were registered anonymously and a urine sample was sent for culture at the microbiological laboratory. The association between the availability of POC tests and the appropriateness of antibiotic prescribing was assessed with multivariable logistic regression., Results: Seventy-six general practices included 1545 patients (83% female); 71% received appropriate treatment in practices with POC culture available and 65% in practices without POC culture available ( p  = 0.042). Having a microscope available was not associated with more appropriate treatment (70% vs. 69%, p  = 0.54)., Conclusion: Availability of POC culture marginally increased appropriate treatment while waiting for the result from the microbiological laboratory. Practices should adopt a strategy where they either perform culture within the practice or send urine for culture at the microbiological laboratory., Trial Registration Number: ClinicalTrials.gov NCT02698332.

Objective: To predict antibiotic use after initial treatment with ibuprofen using data from a randomised controlled trial comparing ibuprofen to pivmecillinam in the treatment of women with symptoms of an uncomplicated urinary tract infection (UTI)., Setting: 16 sites in a primary care setting in Norway, Sweden and Denmark., Participants: Data from 181 non-pregnant women aged 18-60 presenting with symptoms of uncomplicated UTI, initially treated with ibuprofen., Methods: Using the least absolute shrinkage and selection operator logistic regression model, we conducted analyses to see if baseline information could help us predict which women could be treated with ibuprofen without risking treatment failure and which women should be recommended antibiotics., Results: Of the 143 women included in the final analysis, 77 (53.8%) recovered without antibiotics and 66 (46.2 %) were subsequently prescribed antibiotics. In the unadjusted binary logistic regression, the number of days with symptoms before inclusion (<3 days) and feeling moderately unwell or worse (≥4 on a scale of 0-6) were significant predictors for subsequent antibiotic use. In the adjusted model, no predictors were significantly associated with subsequent antibiotic use. The area under the curve of the final model was 0.66 (95% CI: 0.57 to 0.74)., Conclusion: We did not find any baseline information that significantly predicted the use of antibiotic treatment. Identifying women who need antibiotic treatment to manage their uncomplicated UTI is still challenging. Larger data sets are needed to develop models that are more accurate., Trial Registration Number: ClinicalTrials.gov (NCT01849926)., Competing Interests: Competing interests: All authors have completed the International Committee of Medical Journal Editors (ICMJE) uniform disclosure form at http://www.icmje.org/conflicts-of-interest/ and declare: support from The Norwegian Research Council for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to describe and characterize the prescription of antibiotics for urinary tract infection (UTI) in general practice in Denmark and to evaluate compliance with current recommendations., Design: National registry-based study Setting: Danish general practice Patients: 267.539 patients who redeemed a prescription for antibiotics with the clinical indication UTI at community pharmacies between July 1 st 2012 and June 31 st 2013., Main Outcome Measures: Antibiotics prescribed for 1) acute lower UTI, 2) acute upper UTI and 3) recurrent UTI presented as amount of prescriptions, number of treatments per 1000 inhabitants per day (TID) and defined daily doses per 1000 inhabitants per day (DID)., Results: A total of 507.532 prescriptions were issued to 267.539 patients during the one year study period, representing 2.35 DID. Acute lower UTI was the most common reason for prescription of antibiotics (89.5%) followed by recurrent UTI (8.4%). The majority of the prescriptions were issued to people above 60 year old (57.6%). Pivmecillinam was the most commonly prescribed antibiotic in acute lower (45.8%) and acute upper (63.3%) UTI. Trimethroprim was the most commonly prescribed antibiotic in recurrent UTI (45.9%). Prescription of quinolones increased with increasing patient-age (p = <.0001)., Conclusion: Compliance with current Danish recommendations was moderately high. Pivmecillinam is the first line antibiotic for the management of acute lower and upper UTI, and trimethroprim is the first line option of recurrent UTI. A high proportion of the antibiotic prescriptions were issued in the elderly population including a relatively high prescription rate of quinolones. Key points Urinary tract infection (UTI) is a common cause for prescription of antibiotics in general practice Poor compliance in general practice with recommendations for first-line treatment of UTI may increase antibiotic resistance Danish general practitioners are generally compliant with national and regional guidelines for antibiotic treatment of UTI There is high use of antibiotics in the elderly population including a worrisome high use of broad-spectrum antibiotics, such as Quinolones.

Background: Although uncomplicated urinary tract infections (UTIs) are often self-limiting, most patients will be prescribed antibiotic treatment. We assessed whether treatment with ibuprofen was non-inferior to pivmecillinam in achieving symptomatic resolution by day 4, with a non-inferiority margin of 10%., Methods and Findings: This was a randomized, controlled, double-blind non-inferiority trial. We recruited patients from 16 sites in a general practice setting in Norway, Sweden, and Denmark. Non-pregnant women aged 18-60 years presenting with symptoms of uncomplicated UTI were screened for eligibility from 11 April 2013 to 22 April 2016. Patients with informed consent were randomized (1:1 ratio) to treatment with either 600 mg ibuprofen or 200 mg pivmecillinam 3 times a day for 3 days. The patient, treating physician, and study personnel were blinded to treatment allocation. The primary outcome was the proportion of patients who felt cured by day 4, as assessed from a patient diary. Secondary outcomes included the proportion of patients in need of secondary treatment with antibiotics and cases of pyelonephritis. A total of 383 women were randomly assigned to treatment with either ibuprofen (n = 194, 181 analyzed) or pivmecillinam (n = 189, 178 analyzed). By day 4, 38.7% of the patients in the ibuprofen group felt cured versus 73.6% in the pivmecillinam group. The adjusted risk difference with 90% confidence interval was 35% (27% to 43%) in favor of pivmecillinam, which crossed the prespecified non-inferiority margin. Secondary endpoints were generally in favor of pivmecillinam. After 4 weeks' follow-up, 53% of patients in the ibuprofen group recovered without antibiotic treatment. Seven cases of pyelonephritis occurred, all in the ibuprofen group, giving a number needed to harm of 26 (95% CI 13 to 103). Five of these patients were hospitalized and classified as having serious adverse events; 2 recovered as outpatients. A limitation of the study was the extensive list of exclusion criteria, eliminating almost half of the patients screened. We did not register symptoms in the screening process; hence, we do not know the symptom burden for those who declined to participate. This might make our results less generalizable., Conclusions: Ibuprofen was inferior to pivmecillinam for treating uncomplicated UTIs. More than half of the women in the ibuprofen group recovered without antibiotics. However, pyelonephritis occurred in 7 out of 181 women using ibuprofen. Until we can identify those women who will develop complications, we cannot recommend ibuprofen alone as initial treatment to women with uncomplicated UTIs., Trial Registration: ClinicalTrials.gov NCT01849926 EU Clinical Trials Register (EU-CTR), EudraCT Number 2012-002776-14.

Objectives: To investigate the effect of adding point-of-care (POC) susceptibility testing to POC culture on appropriate use of antibiotics as well as clinical and microbiological cure for patients with suspected uncomplicated urinary tract infection (UTI) in general practice., Design: Open, individually randomised controlled trial., Setting: General practice., Participants: Women with suspected uncomplicated UTI, including elderly patients above 65, patients with recurrent UTI and patients with diabetes. The sample size calculation predicted 600 patients were needed., Interventions: Flexicult SSI-Urinary Kit was used for POC culture and susceptibility testing and ID Flexicult was used for POC culture only., Main Outcome Measures: Primary outcome: appropriate antibiotic prescribing on the day after consultation defined as either (1) patient with UTI: to prescribe a first-line antibiotic to which the infecting pathogen was susceptible or a second line if a first line could not be used or (2) patient without UTI: not to prescribe an antibiotic. UTI was defined by typical symptoms and significant growth in a reference urine culture performed at one of two external laboratories., Secondary Outcomes: clinical cure on day five according to a 7-day symptom diary and microbiological cure on day 14. Logistic regression models taking into account clustering within practices were used for analysis., Results: 20 general practices recruited 191 patients for culture and susceptibility testing and 172 for culture only. 63% of the patients had UTI and 12% of these were resistant to the most commonly used antibiotic, pivmecillinam. Patients randomised to culture only received significantly more appropriate treatment (OR: 1.44 (95% CI 1.03 to 1.99), p=0.03). There was no significant difference in clinical or microbiological cure., Conclusions: Adding POC susceptibility testing to POC culture did not improve antibiotic prescribing for patients with suspected uncomplicated UTI in general practice. Susceptibility testing should be reserved for patients at high risk of resistance and complications., Trial Registration Number: NCT02323087; Results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To assess the clinical accuracy (sensitivity (SEN), specificity (SPE), positive predictive value and negative predictive value) of two point-of-care (POC) urine culture tests for the identification of urinary tract infection (UTI) in general practice., Design: Prospective diagnostic accuracy study comparing two index tests (Flexicult™ SSI-Urinary Kit or ID Flexicult™) with a reference standard (urine culture performed in the microbiological department)., Setting: General practice in the Copenhagen area patients. Adult female patients consulting their general practitioner with suspected uncomplicated, symptomatic UTI., Main Outcome Measures: (1) Overall accuracy of POC urine culture in general practice. (2) Individual accuracy of each of the two POC tests in this study. (3) Accuracy of POC urine culture in general practice with enterococci excluded, since enterococci are known to multiply in boric acid used for transportation for the reference standard. (4) Accuracy based on expert reading of photographs of POC urine cultures performed in general practice. Standard culture performed in the microbiological department was used as reference standard for all four measures., Results: Twenty general practices recruited 341 patients with suspected uncomplicated UTI. The overall agreement between index test and reference was 0.76 (CI: 0.71-0.80), SEN 0.88 (CI: 0.83-0.92) and SPE 0.55 (CI: 0.46-0.64). The two POC tests produced similar results individually. Overall agreement with enterococci excluded was 0.82 (0.77-0.86) and agreement between expert readings of photographs and reference results was 0.81 (CI: 0.76-0.85)., Conclusions: POC culture used in general practice has high SEN but low SPE. Low SPE could be due to both misinterpretation in general practice and an imperfect reference standard. Registration number: ClinicalTrials.gov NCT02323087.

Background: Urinary tract infection (UTI) is a common condition in primary care. Patient-reported outcome measures (PROMs) are crucial in the evaluation of interventions to improve diagnosis, treatment and prognosis of UTI. The aim of this study was to identify an existing condition-specific PROM to measure symptom severity, bothersomeness and impact on daily activities for adult patients with suspected urinary tract infection in primary care; or, in the absence of such a PROM, to test items identified from existing PROMs for coverage and relevance in single and group interviews and to psychometrically validate the resulting PROM., Methods: The literature was searched for existing PROMs covering the three domains. Items from the identified PROMs were tested in single and group interviews. The resulting symptom diary was psychometrically validated using the partial credit Rasch model for polytomous items in a cohort of 451 women participating in two studies regarding UTI., Results: No existing PROM fulfilled the inclusion criteria. Content validation resulted in one domain concerning symptom severity (18 items), one concerning bothersomeness (18 items), and one concerning impact on daily activities (7 items). Psychometrical validation resulted in four dimensions in each of the first two domains and one dimension in the third domain., Conclusions: Domains were not unidimensional, which meant that we identified dimensions of patient-experienced UTI that differed substantially from those previously found. We recommend that future studies on UTI, in which PROMs are to be used, should ensure high content validity of their outcome measures and unidimensionality of the included dimensions.

Background: Urinary tract infection (UTI) is a common infection in primary care and is the second leading reason for prescription of antibiotics in Denmark. The diagnosis is often based on symptoms and urine dip-stick, which has limited validity, causing the risk of unnecessary antibiotic prescription. Additionally, with increasing antibiotic resistance, the risk of choosing an antibiotic to which an infecting pathogen is resistant is rising. Combined point-of-care-tests (POCT) for urine culture and susceptibility testing have been developed and validated for primary care, and performing such a test in all patients with suspected UTI in primary care seems rational in order to reduce the use of inappropriate antibiotics. However, the clinical effect of the culture and susceptibility test has not yet been investigated. This study aims to investigate whether POCT urine culture and susceptibility testing decreases the inappropriate use of antibiotics and leads to faster patient recovery., Methods/design: Randomized controlled open label trial of two diagnostic approaches. 750 patients with symptoms of uncomplicated UTI, consecutively contacting their general practitioner (GP), randomized to either POCT urine culture and susceptibility testing and targeted treatment or POCT urine culture without susceptibility testing and empirical treatment. Treatment is started when the POCT is read. The two groups are compared with regard to appropriate choice of antibiotics, clinical remission, and microbiological cure rates., Discussion: The results of this study may provide important evidence to recommend POCT culture and susceptibility testing in all patients with suspected uncomplicated UTI. This could become an additional strategy to fight antibiotic resistance., Trial Registration: ClinicalTrials.gov NCT02323087 .

Misconceptions and knowledge gaps about antibiotics contribute to inappropriate antibiotic use and antimicrobial resistance. This study aimed to identify and prioritize misconceptions and knowledge gaps about antibiotic use from a healthcare professionals' perspective. A modified Delphi study with a predefined list of statements, two questionnaire rounds, and an expert meeting was conducted. The statements were rated by healthcare professionals from France, Greece, Lithuania, Poland, and Spain, and from general practice, out-of-hour services, nursing homes, and pharmacies. A total of 44 pre-defined statements covered the following themes: (1) antimicrobial resistance in general, (2) use of antibiotics in general, (3) use of antibiotics for respiratory tract infections, and (4) use of antibiotics for urinary tract infections. Consensus was defined as ≥80% agreement between the professionals during the second Delphi round. For 30% of the statements, professionals from the four settings together reached consensus. In each setting individually, at least 50% of the statements reached consensus, indicating that there are still many misconceptions and knowledge gaps that need to be addressed. Six educational tools (leaflets, posters, checklists) were developed to address the knowledge gaps and misconceptions. These can be used by patients and healthcare professionals to improve the use of antibiotics in practice. [ABSTRACT FROM AUTHOR]

Background: Resistance to the prescribed antibiotic causes a longer duration of symptoms in patients with urinary tract infection. Yet, a study found that patients infected with trimethoprim-resistant Escherichia coli (E. coli) had a prolonged duration of symptoms even if treated with an antibiotic to which the strain was susceptible. The purpose of this study was to attempt to reproduce this finding in a different cohort. Methods: We analyzed data from two studies from general practice in the Capital Region of Denmark including patients from 2014 to 2016. The primary outcome was the severity of frequency and dysuria. The secondary outcome was the number of days until symptoms had disappeared. Results: We included 180 women treated for uncomplicated cystitis caused by E. coli. We found that 16.11% (n = 29) of the E. coli strains were resistant to all of the three selected antibiotics (ampicillin, sulfamethizole and trimethoprim). There was no significant difference in severity or time until the symptoms had disappeared between women infected with resistant or susceptible E. coli. Conclusions: Strains of E. coli resistant to ampicillin, sulfamethizole and trimethoprim causing uncomplicated cystitis do not result in more severe symptoms or a longer symptom duration if treated with an antibiotic to which they are susceptible. [ABSTRACT FROM AUTHOR]

Uptake was facilitated by the motivation experienced by GPs belonging to primary care networks. Thus, decreasing the inappropriate use of antibiotics in primary care is crucial not only to slow down the spread and development of antibiotic resistance, but also to deliver high quality health care to patients. 10.1002/14651858.CD011825.pub2 2 Costelloe C., Metcalfe C., Lovering A., Mant D., Hay A.D. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: Systematic review and meta-analysis. Primary care accounts for more than 80% of antibiotic use worldwide. [Extracted from the article]

Urinary tract infections (UTIs) are common in nursing home (NH) residents and Denmark is one of the countries with the highest antibiotic use in NHs. The aim of this study was to assess the quality of the diagnostic process and treatment decision on the day of the first contact from NHs to general practice and assess predictors for prescription of antibiotics in NH residents without an indwelling urinary catheter. The study was a prospective observational study in general practice in the Capital Region of Denmark; 490 patients were included; 158 out of 394 (40.1%, 95% CI 35; 45) patients with suspected UTI had urinary tract symptoms; 270 out of 296 (91.2%, 95% CI 87; 94) patients without urinary tract symptoms had a urine culture performed. Performing urine culture in the general practice was inversely associated to prescription of antibiotics on day one (OR 0.27, 95% CI 0.13; 0.56). It is imperative to support the implementation of interventions aimed at improving the quality of the diagnostic process on day one, as less than half of the patients given the diagnosis "suspected UTI" had urinary tract symptoms, and most patients without urinary tract symptoms had a urine culture performed. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented, that suggests careful consideration of over-the-counter nitrofurantoin for self-diagnosed uncomplicated cystitis as it may cause more harm, emphasizing the need for a health professional to assess suspected uncomplicated cystitis and perform diagnostic tests.