Dipstick Tests in the Diagnosis of UTI
Urine culture is the standard for the diagnosis of a UTI, but at least 18 h are needed for detection of bacterial growth and up to 48–72 h until the final result and susceptibilities are available. Reasonably, there has been considerable interest in tests that would predict the culture results rapidly and facilitate the early initiation of therapy. Biochemical analysis of urine for leucocyte esterase (LE) and nitrite by dipstick and microscopy for leucocytes and bacteria have been used for this purpose.[25,26] Dipstick tests involve dipping reagent strips into collected urine. Their advantages over microscopy are ease of use and rapid result time. Numerous studies, reviews and meta-analyses have evaluated their accuracy to predict or exclude a UTI in children (Table 3).[26–30]
LE is released from the white cells in the urine and serves as a surrogate for the microscopic detection of pyuria. A mean sensitivity of 83%, reaching 94% in the context of clinically suspected UTI, has been reported for LE in relation to culture. Its average specificity of 72% suggests that false-positive results due to pyuria of different origin are common. It has been argued that LE is absent in the urine of individuals with asymptomatic bacteriuria (ABU), and this is one of the major advantages of this test. Nitrites are the products of the conversion of urine nitrates by Gram-negative bacteria. Gram-positive cocci do not produce nitrites and would yield a false-negative result. The nitrite test is highly specific but not sensitive, having therefore little value in excluding UTI. The combination of both tests is highly sensitive and specific (Table 3).[9,12,30] Other dipstick tests based on glucose, protein and blood have performed very poorly (Table 3).
Microscopic analysis of a centrifuged urine specimen has been the standard method of assessing pyuria, with a threshold of five white blood cells (WBCs) per high-power field (25 WBCs/μl). Microscopy, especially with a threshold of ten WBCs per high-power field, has been considered more reliable to predict UTI in children <2 years by NICE, Italian and RCH (Royal Children's Hospital) Melbourne guidelines.[13,101,102] A recent meta-analysis, however, did not confirm the advantage of microscopy over the LE dipstick test, a view adopted by the AAP 2011 guideline. The presence of bacteria in a fresh uncentrifuged urine specimen, combined with the use of Gram stain, is considered to be the most reliable rapid test to identify or exclude UTI. Enhanced urinalysis combining WBC counting with hemocytometer in uncentrifuged urine specimens and microscopy of a Gram-stained smear for detection of bacteria has given excellent predictive results, but it requires specialized equipment and trained personnel.
The Best Specimen for Urinalysis
The method of urine collection for a reliable culture in infants and young children remains controversial, but there is an agreement that urinalysis can be performed on any specimen including one obtained by a plastic bag. Indeed, higher sensitivity of dipstick performed on bag specimens than on catheter specimens was found in children <3 years old. Rapid urine tests should be performed on fresh urine with maintenance at room temperature <1 h after voiding or <4 h at refrigeration to be reliable. However, being negative in 10% of children with UTIs, they cannot substitute for culture.
Culture results are considered positive or negative on the basis of colony-forming units per milliliter (CFUs/ml) of grown organisms. The cutoff of positivity for a urine culture obtained by voiding has been >105 CFUs/ml since the 1950s when Kass in his landmark study on adult women found that this cutoff would identify most patients with UTI and would yield the least rate of false positivity. A 1960 pediatric study concluded that the cutoff of >105 CFUs/ml would define UTI in children too, whereas cultures with 103 CFUs/ml rather represented contamination and those with 104–105 CFUs/ml should be repeated. Obviously, these cutoffs cannot be absolute. Given that the time the urine rests in the bladder is an important determinant of the magnitude of the colony count, a proportion of children with true UTI will have cultures with fewer than 105 CFUs/ml.[8,12] Contamination can be a substantial problem particularly in small children, and the different cutoffs of positivity for cultures obtained by plastic bag, transurethral catheterization and suprapubic aspiration (SPA) have been defined on the basis of contamination risk of specimens (Table 4). Culturing more than one specimen or increasing the positivity cutoff from 105 CFUs/ml to 106 or higher have been proposed to increase the likelihood of true infection (Table 4).[3,36,102] In the 2011 AAP guideline, a reduction of the positivity cutoff to 50,000 CFUs/ml is proposed instead, together with the inclusion of pyuria in the diagnostic criteria, which will balance for the decreased specificity of the new cutoff.
The Best Sample for Urine Culture
The method of urine collection from young, nontoilet-trained children has been extensively debated. SPA and transurethral bladder catheterization are unlikely to yield a contamination growth result (Table 4) and are strongly recommended from AAP previous and recent guidelines for children aged <2 years.[3,12] However, these methods are invasive, unpleasant to children, stressful for families, have the risk of complications and are not always feasible as routine procedures in primary care.[13,101] Clean catch urine is proposed from NICE, Italian and RCH Melbourne guidelines as the method of choice for young children in terms of convenience and diagnostic accuracy.[13,101] In comparison with SPA, sensitivity has been calculated to be from 75 to 100% and specificity from 57 to 100%. Urine collection by a plastic bag affixed to the perineum remains popular due to convenience; it can, however, give high rates of false-positive results, even if contamination from skin is minimized through cleansing and prompt bag removal. There are insufficient data regarding comparison of bag specimens to catheter or SPA ones. A recent study reported a sensitivity of 88% and a specificity of 80% for bag samples compared to the reference standard of catheter samples and NICE, Italian and RCH Melbourne guidelines leave room for this method of urine collection as an alternative to clean catch.[13,101,102]
ABU is a well recognized though not clearly defined condition that can further complicate the diagnosis of UTI. ABU mainly affects school-aged girls and also infants.[8,38,39] A minimum of 2.5% of the boys and 0.9% of the girls of a Swedish cohort of infants presented with ABU, which lasted 0.5–7.5 months and resolved spontaneously without any evidence of kidney scarring during the 6-year follow-up period.[39,40] Infants with ABU and fever of a different etiology cannot be easily distinguished from infants with true febrile UTI.[8,12,41] There is evidence that children with ABU will have no pyuria, despite the positive culture.[12,42] The implications of this condition in symptomatic UTI need further evaluation.
Expert Rev Anti Infect Ther. 2012;10(10):1153-1164. © 2012 Expert Reviews Ltd.