title: The Diagnosis of Urinary Tract infection in Young children (DUTY): a diagnostic prospective observational study to derive and validate a clinical algorithm for the diagnosis of urinary tract infection in children presenting to primary care with an acute illness.
abstract: It is not clear which young children presenting acutely unwell to primary care should be investigated for urinary tract infection (UTI) and whether or not dipstick testing should be used to inform antibiotic treatment.
  
  
  
  To develop algorithms to accurately identify pre-school children in whom urine should be obtained; assess whether or not dipstick urinalysis provides additional diagnostic information; and model algorithm cost-effectiveness.
  
  
  
  Multicentre, prospective diagnostic cohort study.
  
  
  
  Children < 5 years old presenting to primary care with an acute illness and/or new urinary symptoms.
  
  
  
  One hundred and seven clinical characteristics (index tests) were recorded from the child's past medical history, symptoms, physical examination signs and urine dipstick test. Prior to dipstick results clinician opinion of UTI likelihood ('clinical diagnosis') and urine sampling and treatment intentions ('clinical judgement') were recorded. All index tests were measured blind to the reference standard, defined as a pure or predominant uropathogen cultured at ≥ 10(5) colony-forming units (CFU)/ml in a single research laboratory. Urine was collected by clean catch (preferred) or nappy pad. Index tests were sequentially evaluated in two groups, stratified by urine collection method: parent-reported symptoms with clinician-reported signs, and urine dipstick results. Diagnostic accuracy was quantified using area under receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) and bootstrap-validated AUROC, and compared with the 'clinician diagnosis' AUROC. Decision-analytic models were used to identify optimal urine sampling strategy compared with 'clinical judgement'.
  
  
  
  A total of 7163 children were recruited, of whom 50% were female and 49% were < 2 years old. Culture results were available for 5017 (70%); 2740 children provided clean-catch samples, 94% of whom were ≥ 2 years old, with 2.2% meeting the UTI definition. Among these, 'clinical diagnosis' correctly identified 46.6% of positive cultures, with 94.7% specificity and an AUROC of 0.77 (95% CI 0.71 to 0.83). Four symptoms, three signs and three dipstick results were independently associated with UTI with an AUROC (95% CI; bootstrap-validated AUROC) of 0.89 (0.85 to 0.95; validated 0.88) for symptoms and signs, increasing to 0.93 (0.90 to 0.97; validated 0.90) with dipstick results. Nappy pad samples were provided from the other 2277 children, of whom 82% were < 2 years old and 1.3% met the UTI definition. 'Clinical diagnosis' correctly identified 13.3% positive cultures, with 98.5% specificity and an AUROC of 0.63 (95% CI 0.53 to 0.72). Four symptoms and two dipstick results were independently associated with UTI, with an AUROC of 0.81 (0.72 to 0.90; validated 0.78) for symptoms, increasing to 0.87 (0.80 to 0.94; validated 0.82) with the dipstick findings. A high specificity threshold for the clean-catch model was more accurate and less costly than, and as effective as, clinical judgement. The additional diagnostic utility of dipstick testing was offset by its costs. The cost-effectiveness of the nappy pad model was not clear-cut.
  
  
  
  Clinicians should prioritise the use of clean-catch sampling as symptoms and signs can cost-effectively improve the identification of UTI in young children where clean catch is possible. Dipstick testing can improve targeting of antibiotic treatment, but at a higher cost than waiting for a laboratory result. Future research is needed to distinguish pathogens from contaminants, assess the impact of the clean-catch algorithm on patient outcomes, and the cost-effectiveness of presumptive versus dipstick versus laboratory-guided antibiotic treatment.
  
  
  
  The National Institute for Health Research Health Technology Assessment programme.
authors.affiliation: Centre for Academic Primary Care, National Institute for Health Research (NIHR) School of Primary Care Research, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Hay
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Birnie
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: John
authors.initials: J
authors.lastname: Busby
authors.affiliation: Department of Primary Care and Public Health Sciences, National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
authors.forename: Brendan
authors.initials: B
authors.lastname: Delaney
authors.affiliation: Centre for Academic Primary Care, National Institute for Health Research (NIHR) School of Primary Care Research, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Harriet
authors.initials: H
authors.lastname: Downing
authors.affiliation: Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Dudley
authors.affiliation: Department of Primary Care and Public Health Sciences, Division of Health and Social Care Research, King's College London, London, UK.
authors.forename: Stevo
authors.initials: S
authors.lastname: Durbaba
authors.affiliation: Centre for Health and Clinical Research, University of the West of England, Bristol, UK.|South West Medicines for Children Local Research Network, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Fletcher
authors.affiliation: Centre for Academic Primary Care, National Institute for Health Research (NIHR) School of Primary Care Research, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Harman
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: William
authors.initials: W
authors.lastname: Hollingworth
authors.affiliation: South East Wales Trials Unit (SEWTU), Institute for Translation, Innovation, Methodology and Engagement, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Kerenza
authors.initials: K
authors.lastname: Hood
authors.affiliation: Specialist Antimicrobial Chemotherapy Unit, Public Health Wales Microbiology Cardiff, University Hospital Wales, Cardiff, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Howe
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Lawton
authors.affiliation: South East Wales Trials Unit (SEWTU), Institute for Translation, Innovation, Methodology and Engagement, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lisles
authors.affiliation: Primary Care and Population Sciences Division, University of Southampton, Southampton, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Little
authors.affiliation: Southmead Hospital, North Bristol NHS Trust, Bristol, UK.
authors.forename: Alasdair
authors.initials: A
authors.lastname: MacGowan
authors.affiliation: Cochrane Institute of Primary Care & Public Health, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: O'Brien
authors.affiliation: South East Wales Trials Unit (SEWTU), Institute for Translation, Innovation, Methodology and Engagement, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Timothy
authors.initials: T
authors.lastname: Pickles
authors.affiliation: Primary Care and Population Sciences Division, University of Southampton, Southampton, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Rumsby
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Jonathan Ac
authors.initials: JA
authors.lastname: Sterne
authors.affiliation: South East Wales Trials Unit (SEWTU), Institute for Translation, Innovation, Methodology and Engagement, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Thomas-Jones
authors.affiliation: Department of Paediatrics and Child Health, University Hospital of Wales, Cardiff, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: van der Voort
authors.affiliation: South East Wales Trials Unit (SEWTU), Institute for Translation, Innovation, Methodology and Engagement, School of Medicine, Cardiff University, Cardiff, UK.
authors.forename: Cherry-Ann
authors.initials: CA
authors.lastname: Waldron
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Penny
authors.initials: P
authors.lastname: Whiting
authors.affiliation: Specialist Antimicrobial Chemotherapy Unit, Public Health Wales Microbiology Cardiff, University Hospital Wales, Cardiff, UK.
authors.forename: Mandy
authors.initials: M
authors.lastname: Wootton
authors.affiliation: Cochrane Institute of Primary Care & Public Health, School of Medicine, Cardiff University, Cardiff, UK.|Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Butler
mesh_terms: D000465:Algorithms; D002675:Child, Preschool; D003362:Cost-Benefit Analysis; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D011320:Primary Health Care / Q000379:methods*; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D014552:Urinary Tract Infections / Q000175:diagnosis*; D059349:Urine Specimen Collection / Q000191:economics* / Q000379:methods* / Q000592:standards