Date Published: February 15, 2017
Publisher: Public Library of Science
Author(s): Kate Birnie, Alastair D. Hay, Mandy Wootton, Robin Howe, Alasdair MacGowan, Penny Whiting, Michael Lawton, Brendan Delaney, Harriet Downing, Jan Dudley, William Hollingworth, Catherine Lisles, Paul Little, Kathryn O’Brien, Timothy Pickles, Kate Rumsby, Emma Thomas-Jones, Judith Van der Voort, Cherry-Ann Waldron, Kim Harman, Kerenza Hood, Christopher C. Butler, Jonathan A. C. Sterne, Martin Chalumeau.
To compare the validity of diagnosis of urinary tract infection (UTI) through urine culture between samples processed in routine health service laboratories and those processed in a research laboratory.
We conducted a prospective diagnostic cohort study in 4808 acutely ill children aged <5 years attending UK primary health care. UTI, defined as pure/predominant growth ≥105 CFU/mL of a uropathogen (the reference standard), was diagnosed at routine health service laboratories and a central research laboratory by culture of urine samples. We calculated areas under the receiver-operator curve (AUC) for UTI predicted by pre-specified symptoms, signs and dipstick test results (the “index test”), separately according to whether samples were obtained by clean catch or nappy (diaper) pads. 251 (5.2%) and 88 (1.8%) children were classified as UTI positive by health service and research laboratories respectively. Agreement between laboratories was moderate (kappa = 0.36; 95% confidence interval [CI] 0.29, 0.43), and better for clean catch (0.54; 0.45, 0.63) than nappy pad samples (0.20; 0.12, 0.28). In clean catch samples, the AUC was lower for health service laboratories (AUC = 0.75; 95% CI 0.69, 0.80) than the research laboratory (0.86; 0.79, 0.92). Values of AUC were lower in nappy pad samples (0.65 [0.61, 0.70] and 0.79 [0.70, 0.88] for health service and research laboratory positivity, respectively) than clean catch samples. The agreement of microbiological diagnosis of UTI comparing routine health service laboratories with a research laboratory was moderate for clean catch samples and poor for nappy pad samples and reliability is lower for nappy pad than for clean catch samples. Positive results from the research laboratory appear more likely to reflect real UTIs than those from routine health service laboratories, many of which (particularly from nappy pad samples) could be due to contamination. Health service laboratories should consider adopting procedures used in the research laboratory for paediatric urine samples. Primary care clinicians should try to obtain clean catch samples, even in very young children.
Urinary tract infection (UTI) affects 6% of acutely unwell children presenting to UK general practice. Timely diagnosis and treatment may alleviate short-term symptoms and could potentially prevent long-term adverse consequences such as renal scarring, impaired renal growth, recurrent pyelonephritis, impaired glomerular filtration, hypertension, end stage renal disease, and pre-eclampsia.[2–4] However establishing a diagnosis in pre- or early-school aged children is challenging; many are pre-verbal and collection of uncontaminated urine samples is difficult. UK National Institute for Health and Clinical Excellence (NICE) guidelines say that a “clean catch” sample is the recommended method for urine collection, but urine collection pads are advised if this is not possible. The American Academy of Pediatrics practice clinical guidelines recommend that urine is collected by catheterization or suprapubic aspiration in young children , but these collection methods are invasive and may be unacceptable to parents, and so are uncommon in UK primary care.
The Diagnosis of Urinary Tract infection in Young children (DUTY) study was a multicentre, prospective, diagnostic cohort study. The methods of recruitment are described in detail in the study protocol. Children were eligible if they were aged <5 years, presented to primary care with any acute illness episode of <28 days duration and had constitutional or urinary symptoms associated with their acute illness. Children were excluded if they were not constitutionally unwell, had a neurogenic or surgically reconstructed bladder, used a urinary catheter, presented with trauma, or had taken antibiotics within the past week. We recruited participants from 233 primary care sites (225 General Practitioner [GP] practices, four Walk-in Centres and four paediatric Emergency Departments) across England and Wales between April 2010 and April 2012. Clinicians were asked to recruit consecutive eligible children. Following written informed parental consent, data were collected on personal details, medical history, presenting symptoms and results of the clinical examination including a clinician-reported global impression of illness severity (score 0–10). Multi-centre ethical approval was granted for this study by the South West Southmead Research Ethics Committee, Ref #09/H0102/64. Of 7163 children recruited to the study, 4828 had results from both laboratories and 4808 had information available on candidate predictors (S1 Fig). The children who were included in this study were older (mean age 29 months) compared to children who were recruited to DUTY, but were not included in this study (mean age 21 months). There were no gender differences (49.0% vs 49.6% male, for those included and not included in our study, respectively), but there was a small difference in ethnicity (83.3% white in our study vs 80.3% white in those who were recruited but not included). Most children who were included in the study (4543, 94.5%) were recruited from GP surgeries (Table 1). There were approximately equal numbers of boys and girls. A total of 2884 children (60%) were aged <3 years and 140 children (2.9%) were aged <3 months. Urine samples were collected using clean catch for 758 (26.3%) of 2884 children aged <3 years and 1861 (96.7%) of 1924 children aged 3–5 years. Among children aged <3 years, samples were obtained in the surgery in 1470 (51.0%) children aged <3 years and 1477 (76.8%) aged 3–5 years. 94% of samples were provided within 24 hours of clinical examinations. Health service laboratory transport systems were faster than the research laboratory with 72.3% vs. 29.6% samples arriving in the laboratory within 24 hours. Parents reported the following symptoms in their children as a moderate or severe problem: pain or crying when passing urine 217 (4.5%), passing urine more often 484 (10.1%), day or bed wetting when previously dry 209 (4.3%) and change in urine appearance 523 (10.9%). A history of UTI was reported in 221 (4.6%) children, 140 of whom were aged ≥3 years. 185 (3.8%) children had a temperature ≥39°C, and fever at any time during the illness was a moderate/severe problem in 2581 (53.7%) participants. Both nitrite (12.9% compared with 2.2%) and leukocyte (16.0% compared with 10.8%) urine dipstick positivity were more common in children aged <3 than ≥3 years. We are not aware of any adverse events resulting from the measurement of “index” or reference tests. Based on a large, unselected cohort of children presenting with acute illness to primary care in England and Wales, reliability of microbiological diagnosis of UTI was worse using nappy pad than clean catch samples. The prevalence of microbiological positivity was much higher for health service laboratories than the research laboratory, particularly for nappy pad samples. Associations of microbiological positivity with pre-specified symptoms, signs and urine dipstick test results were lower for health service laboratories than the research laboratory, and for nappy pad than clean catch samples. The reliability of microbiological diagnosis of UTI thus appears better for the research laboratory than for health service laboratories: these results suggest that many of the positive results reported by health service laboratories, particularly those from nappy pad samples, could be due to contamination. Discrimination improved with increasing bacteriuria concentration and pyuria. Source: http://doi.org/10.1371/journal.pone.0171113