Accepted Article

Article Type: Regular Article

Using a urine dipstick to identify a positive urine culture in young febrile infants is as effective as in older patients

Roberto Velasco, MD1, Helvia Benito, MD1, Rebeca Mozun, MD1, Juan E. Trujillo, MD1, Pedro A. Merino, MD2, Mercedes de la Torre, MD3, Borja Gomez, MD4 on behalf of the Group for the Study of Febrile Infant of the RiSEUP-SPERG Network.

Affiliations: 1Pediatrics Department, Rio Hortega University Hospital, Valladolid, Spain; 2

Intensive Care Unit, Rio Hortega University Hospital, Valladolid, Spain; 3Pediatric

Emergency Department, Niño Jesús University Hospital, Madrid, Spain, 4Pediatric Emergency Department, Cruces University Hospital, Barakaldo, Spain.

Address correspondence to: Roberto Velasco, C/ Pisuerga, 7-3º B, Laguna de Duero, Valladolid, Spain, 47140 [[email protected]], 0034-665-011672

Running head: Detecting positive urine cultures in febrile infants

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/apa.12789 This article is protected by copyright. All rights reserved.

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ABSTRACT Aim There is limited evidence about the diagnostic value of urine dipsticks in young febrile infants. The aim of this study was to determine whether urine dipsticks would identify positive urine cultures in febrile infants of less than 90-days-of-age. Methods This study was a sub-analysis of a prospective multi-centre study developed in 19 Spanish paediatric emergency departments belonging to the Spanish Pediatric Emergency Research Network. It focused on febrile infants of less than 90-days-of-age admitted between October 2011 and September 2013. A positive urine culture was defined as the growth of ≥ 50,000 cfu/ml of a single pathogen collected by a sterile method. Results We included 3,401 patients and 176 (12.8%) female patients and 473 (23.3%) males had a positive urine culture. The leukocyte esterase test showed a mean sensitivity of 82.1% and a mean specificity of 92.4%, with a greater mean negative predictive value for females than males (97.8 versus 94.1%) and a greater mean positive predictive value for males than females (79.4% versus 58%). Conclusion The leukocyte esterase test showed the same accuracy in young febrile infants as previously reported findings for older children. It predicted positive urine cultures and also revealed important gender differences.

Key Words: infants, sensitivity, specificity, urinalysis, urinary tract infections

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Accepted Article

Key Notes: •

There is limited evidence about the diagnostic value of urine dipsticks in young febrile infants and we explored whether they would identify positive urine cultures in those under 90-days-of-age.



We studied 3,401 patients seen in 19 Spanish paediatric emergency departments and the leukocyte esterase test showed the same accuracy in young febrile infants as previously reported in older children.



The test predicted positive urine cultures and revealed important gender differences.

INTRODUCTION Urinary tract infection (UTI) is the most common serious bacterial infection in febrile infants less than 90-days-of-age. Depending on the series, 4–12% of febrile patients in this age group are diagnosed with an UTI (1-3). The gold standard for diagnosing a UTI is a quantitative urine culture, but it has the handicap that its result is not available in the first 48 hours. When a patient is evaluated in a paediatric emergency department, a suspicion diagnosis has to be made as accurately as possible. Several methods have been used, such as urine examination under microscopy or Gram stain, with different results (4-5). However, the most comprehensive method for screening the UTI is the detection of the presence of leukocyte esterase or nitrites in urine, with a urine dipstick analysis (6). Several studies have analysed the accuracy of the urine dipstick for diagnosis of UTI (4-7,14), but most of them include patients older than two- months-of-age. The American Academy of Pediatrics’ guidelines describe sensitivity and specificity values of 93% and 72% for either the presence of leukocyte esterase or nitrites in the urine dipstick in febrile infants between two and 24-months-of-age (7).

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The primary objective of the study was to determine the accuracy of urine dipstick to identify febrile infants of less than 90-days-of-age with a positive urine culture.

METHODS Design of the study This is a sub-analysis of a multi-centre observational prospective study designed to determine the risk of invasive bacterial infection in febrile infants of less than 90-days-of-age with altered urinalysis according to their general appearance, age and laboratory tests (15). Approval for the study and data sharing with the coordinating institution was granted by the institutional review board at each participating institution. Informed consent was obtained from the parents or caregivers of the patients before including them in the study.

Definitions: We used the following definitions. Fever without source (FWS) was defined as axillary or rectal temperature ≥ 38ºC (100.4ºF) registered either at home or at the paediatric emergency department, without catarrhal or other respiratory signs/symptoms (such as tachypnoea) or a diarrhoeal process in patients who underwent a normal physical examination. A leukocyte esterase test was considered as altered if a positive result (> 1+) of a leukocyte esterase test on the urine dipstick was found. Also, a nitrites test was defined as altered when a positive result of a nitrite test on the urine dipstick was found. The threshold for considering a urine culture as positive was the growth of ≥50,000 ufc/ml of a single pathogen in a urine culture collected by a sterile method (urethral catheterisation, suprapubic aspiration) (6). Finally, an invasive bacterial infection (IBI) was defined as the isolation of a bacterial pathogen in blood or cerebrospinal fluid culture. Isolation of

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Accepted Article

Staphylococcus epidermidis, Propionibacterium acnes, Streptococcus viridans or Diphtheroides in immunocompetent patients without cardiac disease, ventricle-peritoneal shunt, central catheters or any other indwelling devices that were considered contaminants. Combur-test® strips (Roche Diagnostics, Basel, Switzerland) were used for the urine test. Urine dipsticks were read by trained nurses in the Emergency Department.

Inclusion criteria: Following local protocols, blood and urine samples were obtained from all infants younger than 90-days-of-age admitted to the paediatric emergency department with FWS. Those who had received tests for C-reactive protein, a white blood cell count, urine dipstick, urine and blood culture during the initial evaluation were included in the study.

Exclusion criteria: We excluded patients for any of the following reasons: a) no collection of urine or blood culture by sterile method, b) no determination of white blood cells count or C-reactive protein values, c) patients in whom the anamnesis and/or the physical examination made by an expert paediatrician suggested the source of the fever, d) afebrile patients who arrived at the paediatric emergency department who had no registered temperature ≥ 38ºC at home, despite parents or caregivers complaining of fever and e) parental refusal to participate. Data collection The following data were collected for every patient included in the study: demographics (age, sex), highest temperature measured at home and on arrival at the paediatric emergency department, duration of the fever before arriving to the paediatric emergency

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Accepted Article

department, appearance of the patient in the initial evaluation, medical history, physical examination, results of laboratory and microbiological tests and the final diagnosis and destination of the patient. A phone call was made to every patient’s parent in order to confirm any unnoticed adverse event. Each investigator also supplied monthly figures on the number of patients and febrile infants who were treated at their hospital. Data were sent to the lead investigator using an on-line Google Drive® platform.

Outcomes The main outcome of the study was the detection of a positive urine culture (see definitions).

Statistical analysis Normally distributed data were expressed as means and standard deviations (SD), nonnormally distributed data were expressed as medians and interquartile ranges and categorical variables were reported as percentages. To compare accuracy of the urine dipstick in young febrile infants, 95% confidence intervals were found and compared with those published in the literature for older patients. To analyse differences between genders, a comparison was performed employing the Mann–Whitney U test for non-normally distributed data and independent samples t-tests for normally distributed data. The χ2 test was used for categorical data. Parameters displaying p

Using a urine dipstick to identify a positive urine culture in young febrile infants is as effective as in older patients.

There is limited evidence about the diagnostic value of urine dipsticks in young febrile infants. The aim of this study was to determine whether urine...
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