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ARTICLE

Automated Urinalysis and Urine Dipstick in the


Emergency Evaluation of Young Febrile Children
AUTHORS: John T. Kanegaye, MD,a,b Jennifer M. Jacob, WHAT’S KNOWN ON THIS SUBJECT: Urinary tract infection is the
MD,a,b and Denise Malicki, MD, PhDa,b,c most common serious bacterial illness among febrile infants and
Departments of aPediatrics and cPathology, University of young children. Automated urine cytometry may supplant
California San Diego School of Medicine, La Jolla, California; and traditional urinalysis, but diagnostic performance at unique
bRady Children’s Hospital San Diego, San Diego, California
pediatric cutpoints has not been described for this labor-saving
KEY WORDS technique.
urinary tract infections, fever, diagnosis, urinalysis, flow
cytometry
WHAT THIS STUDY ADDS: We describe new, clinically useful
ABBREVIATIONS cutpoints for automated leukocyte and bacterial counts. The
AUC—area under the curve
sensitivity and specificity of bacterial counts $250 cells/mL
CI—confidence interval
ED—emergency department exceed those of other methods. However, point-of-care dipstick
LE—leukocyte esterase tests for leukocyte esterase or nitrite have acceptable
LR—likelihood ratio performance.
POC—point-of-care
ROC—receiver operating characteristic
UTI—urinary tract infection
WBC—white blood cell
Drs Jacob and Kanegaye conceived and designed the study and
conducted the data analysis; Dr Jacob conducted the data abstract
collection and prepared the initial draft; Dr Kanegaye critically
reviewed the manuscript and completed the final version of the
OBJECTIVE: The performance of automated flow cytometric urinalysis
draft; and Dr Malicki interpreted data and critically reviewed is not well described in pediatric urinary tract infection. We sought to
and revised the manuscript. All authors approved the final determine the diagnostic performance of automated cell counts and
manuscript as submitted.
emergency department point-of-care (POC) dipstick urinalyses in the
www.pediatrics.org/cgi/doi/10.1542/peds.2013-4222 evaluation of young febrile children.
doi:10.1542/peds.2013-4222
METHODS: We prospectively identified a convenience sample of febrile
Accepted for publication Jun 20, 2014
pediatric emergency department patients ,48 months of age who
Address correspondence to John T. Kanegaye, MD, Division of underwent urethral catheterization to obtain POC and automated
Emergency Medicine, Rady Children’s Hospital San Diego, 3020
Children’s Way (MC 5075), San Diego, CA 92123-4282. E-mail: urinalyses and urine culture. Receiver operating characteristic analyses
jkanegaye@rchsd.org were performed and diagnostic indices were calculated for POC dip-
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). stick and automated cell counts at different cutpoints.
Copyright © 2014 by the American Academy of Pediatrics RESULTS: Of 342 eligible children, 42 (12%) had urinary bacterial
FINANCIAL DISCLOSURE: The authors have indicated they have growth $50 000/mL. The areas under the receiver operating charac-
no financial relationships relevant to this article to disclose. teristic curves were: automated white blood cell count, 0.97; auto-
FUNDING: No external funding. mated bacterial count, 0.998; POC leukocyte esterase, 0.94; and POC
POTENTIAL CONFLICT OF INTEREST: The authors have indicated nitrite, 0.76. Sensitivities and specificities were 86% and 98% for
they have no potential conflicts of interest to disclose. automated leukocyte counts $100/mL and 98% and 98% for bacterial
counts $250/mL. POC urine dipstick with $1+ leukocyte esterase or
positive nitrite had a sensitivity of 95% and a specificity of 98%.
Combinations of white blood cell and bacterial counts did not out-
perform bacterial counts alone.
CONCLUSIONS: Automated leukocyte and bacterial counts performed
well in the diagnosis of urinary tract infection in these febrile pediatric
patients, but POC dipstick may be an acceptable alternative in clinical
settings that require rapid decision-making. Pediatrics 2014;134:523–
529

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Febrile illness is the most common bacterial count cutpoints and to de- Multistix 10 SG, Siemens Corporation,
reason for pediatric emergency de- scribe the performance of point-of- Diagnostics Division, Elkhart, IN), and
partment (ED) visits. The most common care (POC) dipstick urinalyses in the they visually interpreted reagent strips
bacterial source of fever is urinary tract diagnosis of UTI in young febrile ED according to standard color charts.
infection (UTI), with a prevalence of 3% patients ,48 months of age. Urinary nitrite was recorded as positive
to 7% among febrile ED patients ,1 to 2 or negative and leukocyte esterase
years of age1–4 and 8% to 14% among METHODS (LE) as negative, trace, 1+ (small), 2+
febrile infants ,8 weeks of age.5,6 (moderate), or 3+ (large). The speci-
This prospective, observational study
Rapid and accurate identification or mens were then transported by pneu-
was performed from May 15, 2009, to May
exclusion of UTI may improve efficiency matic tube to the clinical laboratory,
15, 2010 in the ED and clinical laboratory
of the ED and acute care for febrile in- where technologists interpreted urine
of a freestanding tertiary children’s
fants, particularly when the diagnostic test strips with the Siemens Clinitek 500
hospital. The ED, with a yearly census of
strategy requires no blood sampling.7,8 ∼65 000, serves as the principal pedi- Urine Chemistry Analyzer (Bayer Cor-
Furthermore, upper tract infection is atric emergency facility for a population poration, Elkhart, IN) and performed
less frequent with early identification of ∼3 million. The institutional review cell counts with the Sysmex UF-1000i
and treatment of UTI.9 board of the University of California San Automated Urine Particle Analyzer
Flow cytometry quantifies the formed Diego approved this study and granted (Sysmex America, Inc, Lincolnshire, IL).
elements in urine and has variable a waiver of informed consent. The UF-1000i quantifies to the nearest
sensitivity and specificity in the diag- 0.1 cell/mL the formed elements in 0.8
We assembled a convenience sample of
nosis of adult UTI.10 Only a small mi- to 1.2 mL of uncentrifuged urine based
children ,48 months old who pre-
nority (15%) of hospital laboratories on size, shape, and staining charac-
sented to the ED with fever and a clini-
use automated cytometry to reduce teristics.16,19,20 Technologists verified
cal need to evaluate for UTI. Attending
reliance on labor-intensive manual automated WBC counts .20/mL man-
physicians ordered laboratory analysis
microscopic urinalyses,11 but the 2011 ually by using hemocytometer slides.
and prescribed treatment at their dis-
American Academy of Pediatrics clini- Using standard quantitative culture
cretion. Patients were included who
methods, a positive urine culture result
cal practice guideline for UTI predicts had temperatures $38°C in the ED or
that automated methods will become was defined as growth of $50 000
tactile or documented fevers at home
the most common laboratory-based CFU/mL of a urinary pathogen. Urine
within 24 hours and who underwent
method of diagnosis.12 Pediatric refer- cultures with growth of normal flora,
urethral catheterization to obtain sam-
ence ranges for automated white blood ples for POC dipstick testing, auto- mixed organisms, or ,50 000 CFU/mL of
cell (WBC) and bacterial counts, estab- mated urinalyses, and urine cultures. a pathogen were considered negative.
lished without culture confirmation,13,14 Patients were excluded who had in- Data collected during the ED visit in-
may not define a clinically meaningful complete data or urine testing, who cluded age, gender, medical history,
risk of pediatric UTI. Children comprised had received systemic antibiotics in the maximum home and ED temperatures,
only 4% to 9% of populations that de- previous 24 hours, who were immu- and results of POC and automated
fined cutpoints for flow cytometric uri- nocompromised or at risk for neu- dipstick testing and automated WBC
nalysis against a culture standard.15,16 tropenia, or who had conditions that counts. We obtained culture results
One pediatric study that evaluated au- predispose to asymptomatic genitouri- from the electronic medical record and
tomated cell counts with a culture nary bacterial colonization (including reviewed all UF-1000i printouts to con-
standard applied adult reference val- neurogenic bladder, chronic or inter- firm the reported automated WBC
ues to an older (median age: 10 years), mittent bladder instrumentation, or counts and to obtain manual WBC and
unselected subspecialty cohort.17 A surgical diversion of the urinary tract). automated bacterial counts not re-
recent comparison of automated digi- Patients with risk factors for acute ported in the medical record.
tal microscopy and enhanced urinaly- symptomatic UTI who generally had Primary outcome measures included
sis among pediatric ED patients18 used acellular, sterile urine between infec- the POC LE and nitrite results, auto-
cutpoints derived from manual mi- tions and whose initial evaluation and mated urine WBC and bacterial counts,
croscopy.3 Because test performance treatment are similar to those of other and urine culture results. Our sample
varies with threshold, we sought to febrile patients were included. size was determined by using precision
determine performance of urine flow Competency-verified ED nurses per- of calculated sensitivity. Based on a
cytometry over a range of WBC and formed POC dipstick testing (Siemens previously observed 13% prevalence of

524 KANEGAYE et al
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ARTICLE

UTIs in febrile children in our ED, we organisms or low growth, and none only 33 samples (10%) (Fig 1). In only 2
calculated that a sample size of 375 resulted in antibiotic treatment of UTI. culture-negative cases did manual and
patients would yield 95% confidence Except for characteristics known to automated WBC counts lie on opposite
intervals (CIs) 610% around a point influence the risk of UTI,24 patients with sides of the cutpoint of 100 cells/mL; for
estimate for a sensitivity of 85%. A re- and without UTI had similar pretest 92% of differences, automated counts
ceiver operating characteristic (ROC) clinical features (Table 1). were higher than manual counts.
analysis was performed of the ability of POC and laboratory results agreed in In the ROC analysis, all urine test results
POC LE and nitrite measurements and 98.5% of nitrite and 98.0% of LE de- except nitrite had areas under the curve
automated WBC and bacterial counts to terminations. Of the 5 patients with (AUCs) $0.94, and the AUC for the
predict urine cultures yielding $50 000 POC-positive, laboratory-negative ni- bacterial count was highest. AUCs (with
CFU/mL. For analysis of test perfor- trite results, 4 had growth of pathogens 95% CIs) were as follows: WBC, 0.97
mance at different thresholds, WBC $105 CFU/mL, and the fifth received (0.95–0.99); bacteria, 0.998 (0.996–0.999);
and bacterial counts were rounded antibiotics after the culture yielded POC LE, 0.94 (0.89–0.996); and POC ni-
to whole numbers, and we calculated 30 000 CFU/mL of E coli. For the 10 POC- trite, 0.76 (0.66–0.86).
sensitivity, specificity, and negative and LE–positive, culture-negative specimens, Favorable sensitivityandspecificitypairs
positive likelihood ratios (LRs). To inform 6 corresponding laboratory LE test re- resulted from selected thresholds for
clinicians who must integrate multiple sults were positive, including all 4 with POC dipstick and automated cell counts
urine test results, we calculated the POC LE $1+ and 2 of 6 trace positive in the diagnosis of UTI (Table 2). POC
same indices for combinations of POC tests. Three laboratory trace–LE-positive, dipsticks with $1+ LE or positive ni-
LE and nitrites and combinations of culture-negative specimens had cor- trite yielded a sensitivity of 0.95 and a
WBC and bacterial counts. Because responding negative POC results. All 4 specificity of 0.98. Clinically practical
reported sensitivity varies widely for POC-LE–negative,culture-positivespeci- cytometric thresholds were 100 cells/mL
patients ,3 months of age,1,5,6,21 and mens were LE-negative according to for automated WBC counts (sensitivity:
because current teaching commonly the laboratory. Automated cytometry 0.86; specificity: 0.98) and 250 cells/mL
cites increased false-negative rates for
counts ranged from 0 to 39 374/mL for for automated bacterial counts (sen-
young infants and children,22,23 indices
WBC and 0 to 54 445/mL for bacteria sitivity: 0.98; specificity: 0.98). Higher
were calculated for the subset of pa-
(Table 1). Concurrent manual hemocy- bacterial count thresholds improved
tients 0 to 90 days of age.
tometer WBC counts on 323 samples specificities and LRs minimally with a
(94%) differed from the automated substantial decrease in sensitivity. Among
RESULTS counts by $10% in 58 (18%). However, the 72 patients aged 0 to 90 days with 11
the differences exceeded 10 cells/mL in UTIs, comparable performance occurred
Of 476 eligible patients, 134 (28%) were
excluded because urine testing was
incomplete or the printout containing TABLE 1 Characteristics of the 342 Study Patients
bacterial counts was not available. Of Characteristic UTI (N = 42) No UTI (N = 300) Combined
the 342 remaining patients, 42 (12.3%) Age, mo, median (IQR) 6.2 (3.1–12.1) 8.2 (3.7–14.3) 8.1 (3.6–14.3)
Female gender, n (%) 24 (57) 178 (59) 202 (59)
had cultures positive for Escherichia
Circumcised males, n/N (%)a 2/18 (11) 36/111 (32) 38/129 (29)
coli (n = 37), Klebsiella pneumoniae Maximum home temperature, °C, mean 6 SDb 39.1 6 0.7 39.0 6 0.8 39.0 6 0.8
(n = 3), Klebsiella oxytoca (n = 1), and Maximum ED temperature, °C, mean 6 SD 38.8 6 0.9 38.7 6 1.1 38.8 6 1.1
Enterococcus faecium (n = 1). The uri- Previous UTI, n (%) 8 (19) 15 (5) 23 (7)
Genitourinary abnormalities, n (%)c 4 (10) 6 (2) 10 (3)
nalysis for the ampicillin-sensitive en- Automated WBC count, cells/mL
terococcal isolate was negative for LE Median (IQR) 1433 (393–5694) 12 (6–20) 13 (6–26)
and nitrite and had 19 WBC/mL and 337 Range 18–39 374 0–881 0–39 374
Automated bacterial count, cells/mL
bacteria/mL. Four patients had single Median (IQR) 7138 (2074–14 095) 18 (11–38) 20 (11–60)
urinary pathogens in concentrations Range 140–54 445 1–1905 1–54 445
,50 000 CFU/mL, and 1 had .4 or- ED diagnosis of UTI, n (%) 40 (95) 7 (2) 47 (14)
ganisms at a concentration $60 000 IQR, interquartile range.
a Male circumcision status presented as number circumcised per number of male patients. Data were missing for 11
CFU/mL. All 5 had positive POC nitrite or patients in the non-UTI group. UTI rate among uncircumcised boys was 16 (18%) of 91 patients; among circumcised boys, it
LE, 4 had high WBC or bacterial counts, was 2 (5%) of 38.
b Home temperature measurements were available in 31 patients in the UTI group and in 255 patients in the non-UTI group.
and all received antibiotic therapy for c Abnormalities among UTI group: vesicoureteral reflux, history of nephrolithiasis, dysplastic kidney, and hydronephrosis;

UTI. Twenty-seven cultures yielded mixed among non-UTI group: duplex collecting system (2), vesicoureteral reflux, dysplastic kidney (2), hypospadias repair.

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cytometry and POC dipstick among
young febrile children evaluated for UTI
in a pediatric ED. Automated bacterial
counts exhibited the best ability to diag-
nose UTI. A bacterial cutpoint of 100/mL
had a sensitivity of 1.0 and a specificity
of 0.95, and a cutpoint of 250/mL pro-
duced a clinically useful high-sensitivity,
high-specificity combination (0.98 for
both). Automated WBCs began to have
useful LRs at counts $100/mL. How-
ever, the combination of POC dipstick
LE and nitrites, although slightly less
sensitive, had acceptable diagnostic
performance and may be an attractive
alternative option when manual or auto-
FIGURE 1 mated microscopic urinalysis is not
Scatter plot of manual microscopic WBC counts against automated WBC counts (r = 0.999). available or practical. POC and auto-
mated tests performed well in the
at thresholds of POC LE $1+ (sensitiv- (Table 3). No combination of WBC count subset of patients 0 to 90 days of age.
ity: 1.0 [95% CI: 0.74–1.0]; specificity: $10/mL and bacteria at any concen- Most studies of automated urinalysis
0.93 [95% CI: 0.84–0.97]), $100 WBC/mL tration outperformed the automated predominantly involve adults and often
(sensitivity: 0.91 [95% CI: 0.62–0.98]; bacterial count alone. Combinations of include hospitalized, elderly, or unchar-
specificity: 0.95 [95% CI: 0.87–0.98]), high WBC and bacterial counts achieved acterized patients.10,16,19 Children ,16
and $250 bacteria/mL (sensitivity: 1.0 specificities as high as 0.993 with sen- years of age comprised 9% of a com-
[95% CI: 0.74–1.0]; and specificity: 0. 95 sitivities ranging from 0.79 to 0.83. bined adult and pediatric study pop-
[95% CI: 0.87–0.98]). ulation for which a combination of $15
At the threshold of 10 WBC/mL used for WBC/mL or $500 bacteria/mL yielded
the enhanced urinalysis,25,26 sensitivity DISCUSSION a sensitivity of 0.98 and a specificity
of the automated WBC count increased In this study, we report the excellent of 0.25 for urine bacterial growth
to 1.0, but specificity decreased to 0.40 diagnostic performances of automated $103/mL.15 Patients ,3 years of age

TABLE 2 Test Characteristics of POC Dipstick and Automated Cell Count Urinalyses
Test and Threshold Sensitivity Specificity LR + LR –
POC tests
Nitrites 22/42 (0.52), 0.38–0.67 298/300 (0.99), 0.98–0.998 78.6, 19.2–322.2 0.48, 0.35–0.66
LE $ trace 38/42 (0.91), 0.78–0.96 290/300 (0.97), 0.94–0.98 27.1, 14.6–50.3 0.10, 0.04–0.25
LE $ trace OR nitrite positive 40/42 (0.95), 0.84–0.99 289/300 (0.96), 0.94–0.98 26.0, 14.5–46.6 0.05, 0.01–0.19
LE $1+ 37/42 (0.88), 0.75–0.95 296/300 (0.99), 0.97–0.995 66.1, 24.8–176.0 0.12, 0.05–0.27
LE $1+ OR nitrite positive 40/42 (0.95), 0.84–0.99 295/300 (0.98), 0.96–0.99 57.1, 23.9–136.6 0.05, 0.01–0.19
LE $2+ 35/42 (0.83), 0.69–0.92 297/300 (0.99), 0.97–0.997 83.3, 26.8–259.0 0.17, 0.09–0.33
LE $2+ OR nitrite positive 39/42 (0.93), 0.81–0.98 296/300 (0.99), 0.97–0.995 69.6, 26.2–185.0 0.07 0.02–0.22
Automated counts
WBC $10 cells/mL 42/42 (1.0), 0.92–1.0 120/300 (0.40), 0.35–0.46 1.7, 1.5–1.8 0.0 —
WBC $25 cells/mL 39/42 (0.93), 0.81–0.98 246/300 (0.82), 0.77–0.86 5.2, 4.0–6.7 0.09, 0.03–0.26
WBC $50 cells/mL 36/42 (0.86), 0.72–0.93 285/300 (0.95), 0.92–0.97 17.1, 10.3–28.5 0.15, 0.07–0.32
WBC $100 cells/mL 36/42 (0.86), 0.72–0.93 294/300 (0.98), 0.96–0.99 42.9, 19.2–95.5 0.15, 0.07–0.31
WBC $200 cells/mL 34/42 (0.81), 0.67–0.90 295/300 (0.98), 0.96–0.99 48.6, 20.1–117.3 0.19, 0.10–0.36
Bacteria $50 cells/mL 42/42 (1.0), 0.92–1.0 244/300 (0.81), 0.77–0.85 5.4, 4.2–6.8 0.0 —
Bacteria $100 cells/mL 42/42 (1.0), 0.92–1.0 285/300 (0.95), 0.92–0.97 20.0, 12.2–32.8 0.0 —
Bacteria $250 cells/mL 41/42 (0.98), 0.88–0.996 294/300 (0.98), 0.96–0.99 48.8, 22.1–107.9 0.02, 0–0.17
Bacteria $500 cells/mL 39/42 (0.93), 0.81–0.98 295/300 (0.98), 0.96–0.99 55.7, 23.3–133.4 0.07, 0.02–0.22
Sensitivity presented as true-positives per number with UTI and specificity as true-negatives per number without UTI with point estimates and 95% CIs for proportions. LRs presented with 95%
CIs, except when a zero term appears in a denominator. LR +, LR of positive test result; LR –, LR of negative test result.

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TABLE 3 Test Characteristics of Combinations of Automated WBC and Bacterial Counts


Test and Threshold Sensitivity Specificity LR + LR –
WBC $10 cells/mL 42/42 (1.0), 0.92–1.0 120/300 (0.40), 0.35–0.46 1.7, 1.5–1.8 0.0 —
WBC $10 cells/mL and bacteria $50 cells/mL 42/42 (1.0), 0.92–1.0 247/300 (0.82), 0.78–0.86 5.7, 4.4–7.2 0.0 —
WBC $10 cells/mL and bacteria $100 cells/mL 42/42 (1.0), 0.92–1.0 286/300 (0.95), 0.92–0.97 21.4, 12.9–35.7 0.0 —
WBC $10 cells/mL and bacteria $250 cells/mL 41/42 (0.98), 0.88–0.996 294/300 (0.98), 0.96–0.99 48.8, 22.1–107.9 0.02, 0–0.17
WBC $10 cells/mL and bacteria $500 cells/mL 39/42 (0.93), 0.81–0.98 295/300 (0.98), 0.96–0.99 55.7, 23.3–133.4 0.07, 0.02–0.22
WBC $25 cells/mL and bacteria $100 cells/mL 39/42 (0.93), 0.81–0.98 293/300 (0.98), 0.95–0.99 39.8, 19.1–83.2 0.07, 0.02–0.22
WBC $25 cells/mL and bacteria $250 cells/mL 38/42 (0.91), 0.78–0.96 297/300 (0.99), 0.97–0.997 90.5, 29.2–280.1 0.10, 0.04–0.24
WBC $50 cells/mL and bacteria $100 cells/mL 36/42 (0.86), 0.72–0.93 294/300 (0.98), 0.96–0.99 42.9, 19.2–95.5 0.15, 0.07–0.31
WBC $50 cells/mL and bacteria $250 cells/mL 35/42 (0.83), 0.69–0.92 297/300 (0.99), 0.97–0.997 83.3, 26.8–259.0 0.17, 0.09–0.33
WBC $100 cells/mL and bacteria $100 cells/mL 36/42 (0.86), 0.72–0.93 295/300 (0.98), 0.96–0.99 51.4, 21.4–123.7 0.15, 0.07–0.30
WBC $100 cells/mL and bacteria $250 cells/mL 35/42 (0.83), 0.69–0.92 298/300 (0.99), 0.98–0.998 125.0, 31.2–500.8 0.17, 0.09–0.33
WBC $200 cells/mL and bacteria $250 cells/mL 34/42 (0.81), 0.67–0.90 298/300 (0.99), 0.98–0.998 121.4, 30.3–487.1 0.19, 0.10–0.36
WBC $250 cells/mL and bacteria $250 cells/mL 33/42 (0.79), 0.64–0.88 298/300 (0.99), 0.98–0.998 117.9, 29.4–473.3 0.22, 0.12–0.38
Sensitivity presented as true-positives per number with UTI and specificity as true-negatives per number without UTI with point estimates and 95% CIs for proportions. LRs presented with 95%
CIs, except when a zero term appears in a denominator. LR +, LR of positive test result; LR –, LR of negative test result.

comprised 4% of a population that pro- are not practical. An ED POC dipstick obtained by using less invasive meth-
duced sensitivities and specificities of cutpoint of $1+ LE or positive nitrite ods.
0.99 and 0.77 respectively, for WBC counts had moderately high sensitivity (0.85) We reasoned that automated cytometry
$150/mL and 0.97 and 0.80 respec- but low specificity (0.53) in a high- would be similar to manual hemocy-
tively, for bacterial counts $150/mL.16 prevalence population of symptomatic tometer counts as measures of particle
However, neither study reported the adult women.27 Even with sensitivity as concentration in uncentrifuged urine.
clinical features or results of the pe- low as 79%, urine dipstick paired with Strong correlations have been reported
diatric subsets. Automated urinalyses culture may be an adequate, cost- between cell counts performed by using
performed on noncatheterized sam- effective screen for UTI in young chil- UF-1000i and those by microscopy per-
ples from pediatric nephrology and dren.26 Laboratory-based determinations formed by using a counting chamber.20
urology patients predominantly $3 of LE28 and combinations of LE and ni- Leukocyte counts by hemocytometer
years of age yielded a sensitivity of 0.89 trite29,30 performed similarly to micro- had better sensitivity and specificity6,25,32
and a specificity of 0.85 with the use of scopic urinalysis in detection of UTI in and ROC AUCs6,32 than those according
an adult bacterial cutpoint and an un- infants and young children. Automated to standard urinalysis in the detection
clear WBC cutpoint.17 Patients’ symp- dipstick heme and LE measurements of UTI in febrile infants. The continuous
toms were not described, and 37% of have statistically significant correla- and precise WBC counts provided by
those with positive urine culture tions with automated erythrocyte and using automated methods will likely
results did not receive treatment for WBC counts.31 Our findings similarly prove less labor intensive and more
a UTI. Automated digital microscopy demonstrate that the sensitivity and versatile and will provide more useful
diagnosed nonenterococcal pediatric specificity of POC dipstick urinalysis risk stratification than single cutpoints
UTI with sensitivities and specificities approach those of automated cyto- of 10 WBC/mL6,25,26,32 or 5 WBC/high-
of 0.89 and 0.9, respectively, at a WBC metric urinalysis and may provide an power field1,25,26 for uncentrifuged and
cutpoint of 2/high-power field and 0.79 adequate screen for UTI among febrile centrifuged samples, respectively. We
and 0.85, respectively, for detection of children in the ED, urgent care, or pri- did not examine centrifuged urine or
any bacteria.18 We expanded on pre- mary care setting. Positive POC test perform Gram-stain analysis and could
vious work by using catheter collection results justify antibiotic therapy with- not compare automated cytometry
and a culture standard to determine out formal urinalysis, and negative POC with enhanced urinalyses or the more
unique optimal cutpoints for automated or automated test results may allow familiar standard urinalysis. However,
cytometric WBC and bacterial counts clinicians to withhold antibiotic ther- unblinded manual hemocytometer
among young febrile outpatients at apy pending culture results. In addi- counts were within 10 cell/mL of 90% of
risk for UTI. tion, negative POC urinalysis results our automated WBC counts, and auto-
POC dipstick testing may be preferable may obviate the need for laboratory- mated bacterial counts may provide
in clinical settings in which rapid based tests or cultures in well-appearing a highly precise substitute for the in-
decision-making is required or where children at low risk for complications spection of Gram-stained urine for
microscopic or automated techniques of UTI, especially with specimens bacteria.

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Our study design likely contributed to as age, gender, circumcision status, and growth or who wish to incorporate
its favorable results. We enrolled a height and duration of fever,24 our data urinalysis into the interpretation of
narrowly defined population of young cannot be used to estimate prevalence positive urine culture results. Our flow
febrile patients whose prospectively or identify clinical predictors. Noncon- cytometric data cannot be generalized
identified clinical characteristics con- secutive enrollment and the exclusion directly to WBC counts obtained by
stituted a reasonable suspicion for of patients with incomplete urine test- enhanced urinalysis or digital imag-
acute untreated UTI and who uniformly ing or data could have led to nonrep- ing,18 but our experience suggests that
underwent bladder catheterization. resentative sampling but were unlikely alternate thresholds exist for those
Previous studies have lacked clinical to have systematically selected urine methods. In addition, we cannot predict
exclusion criteria,13–15,17,29 obtained clin- specimens with altered test perfor- the ability of POC or automated meth-
ical data or exclusion criteria by using mance characteristics. ods to identify enterococcal infections,
retrospective chart review,1,18 or did Because our POCdata result from routine which provoke a less pyogenic re-
not specifically exclude patients with clinical testing, we did not measure sponse.18 Unlike other authors,9,33,38 we
antibiotic pretreatment.1,3,25,26,33 Non- interrater reliability or the accuracy of did not attempt to identify asymptom-
catheter collection methods contributed individual nurses. However, the ob- atic bacteriuria or to differentiate py-
some1,5 or nearly all13,14,17 specimens in served agreement between POC and elonephritis from cystitis. However, few
previous studies. Technologists tested laboratory determinations suggests clinicians using highly sensitive and
our specimens upon receipt rather excellent reliability. The unexpected specific rapid urine tests would dis-
than storing them for batch-testing.18,26 differences between automated and continue therapy if scintigraphic stud-
POC testing by ED nurses or pediatric microscopic WBC counts likely reflect ies reveal no renal involvement.
trainees5,27 is subject to operator vari- improved precision due to the 103- to
ability; however, all ED nurses perform- 104-fold greater sampling volumes of CONCLUSIONS
ing our POC tests underwent competency automated analyzers (0.8–1.2 mL) over Using automated flow cytometry on
verification. Although inconsistent per- counting chambers (0.1–0.9 mL) and catheterized urine samples from febrile
formance of urinalyses in patients #3 caused no loss of sensitivity. young ED patients at risk for UTI, bac-
months of age1,5,6,21 has caused con- Although we used a well-established terial counts $250 cells/mL have the
cern for lower sensitivity,22,23 our uni- definition of UTI as $50 000 CFU/mL best combination of sensitivity and
form study conditions resulted in of a single urinary pathogen for speci- specificity. However, a POC dipstick
excellent performance in the subset of mens obtained according to catheter,3,25 with $1+ LE or positive nitrite pro-
patients aged 0 to 90 days. other definitions use bacterial concen- duced a favorable performance and
We recognize several limitations to our trations $10 000/mL1,2,5,26,34 or combi- may be an acceptable screen for UTI in
study, which was conducted in a high- nations of growth at 10 000 to ,50 000 the ED and other outpatient settings in
volume, tertiary pediatric ED in which CFU/mL,35,36 $50 000 CFU/mL,12 or which pediatric patients are evaluated
clinical staff were experienced in POC $100 000 CFU/mL37 with positive uri- for febrile illnesses.
testing. Other clinical settings with nalyses. Because we used a moderately
lower patient volumes or less experi- stringent bacteriologic criterion and ACKNOWLEDGMENTS
ence using POC urine dipstick or excluded the tests under evaluation The authors thank Erin M. Fletcher, BS,
cytometry may be unable to replicate from the definition of UTI, our results for management of the database and
our results. Because clinicians ordered may be less helpful to clinicians who Robert H. Riffenburgh, PhD, for assis-
tests based on clinical risk factors, such wish to treat at lower levels of bacterial tance in planning the statistical analysis.

REFERENCES
1. Bachur R, Harper MB. Reliability of the 3. Hoberman A, Wald ER, Reynolds EA, Penchansky the emergency department. Pediatrics.
urinalysis for predicting urinary tract L, Charron M. Pyuria and bacteriuria in urine 1998;102(2). Available at: www.pediatrics.
infections in young febrile children. Arch specimens obtained by catheter from young org/cgi/content/full/102/2/e16
Pediatr Adolesc Med. 2001;155(1):60–65 children with fever. J Pediatr. 1994;124(4): 5. Crain EF, Gershel JC. Urinary tract infec-
2. Hoberman A, Chao HP, Keller DM, Hickey R, 513–519 tions in febrile infants younger than 8 weeks
Davis HW, Ellis D. Prevalence of urinary 4. Shaw KN, Gorelick M, McGowan KL, Yakscoe of age. Pediatrics. 1990;86(3):363–367
tract infection in febrile infants. J Pediatr. NM, Schwartz JS. Prevalence of urinary 6. Lin DS, Huang SH, Lin CC, et al. Urinary tract
1993;123(1):17–23 tract infection in febrile young children in infection in febrile infants younger than

528 KANEGAYE et al
Downloaded from www.aappublications.org/news at Univ Of Virginia on November 4, 2019
ARTICLE

eight weeks of age. Pediatrics. 2000;105(2). diagnosis of urinary tract infection. Arch 29. Armengol CE, Hendley JO, Schlager TA.
Available at: www.pediatrics.org/cgi/content/ Dis Child. 2010;95(3):193–197 Should we abandon standard microscopy
full/105/2/e20 18. Shah AP, Cobb BT, Lower DR, et al. Enhanced when screening for urinary tract infections
7. Baraff LJ. Management of fever without versus automated urinalysis for screening in young children? Pediatr Infect Dis J.
source in infants and children. Ann Emerg of urinary tract infections in children in the 2001;20(12):1176–1177
Med. 2000;36(6):602–614 emergency department. Pediatr Infect Dis 30. Shaw KN, Hexter D, McGowan KL, Schwartz
8. Ishimine P. Fever without source in chil- J. 2014;33(3):272–275 JS. Clinical evaluation of a rapid screening
dren 0 to 36 months of age. Pediatr Clin 19. Manoni F, Fornasiero L, Ercolin M, et al. test for urinary tract infections in children.
North Am. 2006;53(2):167–194 Cutoff values for bacteria and leukocytes J Pediatr. 1991;118(5):733–736
9. Doganis D, Siafas K, Mavrikou M, et al. Does for urine flow cytometer Sysmex UF-1000i 31. Langlois MR, Delanghe JR, Steyaert SR,
early treatment of urinary tract infection in urinary tract infections. Diagn Microbiol Everaert KC, De Buyzere ML. Automated
prevent renal damage? Pediatrics. 2007; Infect Dis. 2009;65(2):103–107 flow cytometry compared with an auto-
120(4). Available at: www.pediatrics.org/ 20. Manoni F, Tinello A, Fornasiero L, et al. mated dipstick reader for urinalysis. Clin
cgi/content/full/120/4/e922 Urine particle evaluation: a comparison be- Chem. 1999;45(1):118–122
10. Shang YJ, Wang QQ, Zhang JR, et al. Sys- tween the UF-1000i and quantitative micros- 32. Lin DS, Huang FY, Chiu NC, et al. Comparison
tematic review and meta-analysis of flow copy. Clin Chem Lab Med. 2010;48(8):1107–1111 of hemocytometer leukocyte counts and
cytometry in urinary tract infection 21. Bonadio W, Maida G. Urinary tract infection standard urinalyses for predicting urinary
screening. Clin Chim Acta. 2013;424:90–95 in outpatient febrile infants younger than tract infections in febrile infants. Pediatr
11. Tworek JA, Wilkinson DS, Walsh MK. The 30 days of age: a 10-year evaluation. Infect Dis J. 2000;19(3):223–227
rate of manual microscopic examination of Pediatr Infect Dis J. 2014;33(4):342–344
33. Hoberman A, Wald ER, Reynolds EA,
urine sediment: a College of American 22. Krasinski KM. Urinary tract infections. In: Penchansky L, Charron M. Is urine culture
Pathologists Q-Probes study of 11,243 uri- Rudolph CD, Rudolph AM, Lister GE, First LR, necessary to rule out urinary tract in-
nalysis tests from 88 institutions. Arch Gershon AA, eds. Rudolph’s Pediatrics. 22nd
fection in young febrile children? Pediatr
Pathol Lab Med. 2008;132(12):1868–1873 ed. New York, NY: McGraw-Hill Medical;
Infect Dis J. 1996;15(4):304–309
12. Roberts KB; Subcommittee on Urinary Tract 2011:950–956
34. Gorelick MH, Shaw KN. Screening tests for
Infection, Steering Committee on Quality 23. McCollough M, Sharieff GQ. Genitourinary
urinary tract infection in children: a meta-
Improvement and Management. Urinary and renal tract disorders. In: Marx JA,
analysis. Pediatrics. 1999;104(5). Available at:
tract infection: clinical practice guideline Hockberger RS, Walls RM, eds. Rosen’s
www.pediatrics.org/cgi/content/full/104/5/e54
for the diagnosis and management of the Emergency Medicine: Concepts and Clinical
initial UTI in febrile infants and children 2 to Practice. 8th ed. Philadelphia, PA: Elsevier 35. Schnadower D, Kuppermann N, Macias CG,
24 months. Pediatrics. 2011;128(3):595–610 Saunders; 2013:2205–2223 et al; American Academy of Pediatrics Pe-
diatric Emergency Medicine Collaborative
13. Lun A, Ziebig R, Hammer H, Otting U, Filler 24. Shaikh N, Morone NE, Lopez J, et al. Does
G, Sinha P. Reference values for neonates this child have a urinary tract infection? Research Committee. Febrile infants with
and children for the UF-100 urine flow JAMA. 2007;298(24):2895–2904 urinary tract infections at very low risk for
cytometer. Clin Chem. 1999;45(10):1879–1880 adverse events and bacteremia. Pediatrics.
25. Hoberman A, Wald ER, Penchansky L,
2010;126(6):1074–1083
14. Manoni F, Gessoni G, Caleffi A, et al. Pedi- Reynolds EA, Young S. Enhanced urinalysis
atric reference values for urine particle as a screening test for urinary tract in- 36. Zorc JJ, Levine DA, Platt SL, et al; Multi-
quantification by using automated flow fection. Pediatrics. 1993;91(6):1196–1199 center RSV-SBI Study Group of the Pediatric
cytometer: results of a multicenter study of 26. Shaw KN, McGowan KL, Gorelick MH, Emergency Medicine Collaborative Research
Italian urinalysis group. Clin Biochem. 2013; Schwartz JS. Screening for urinary tract Committee of the American Academy of Pe-
46(18):1820–1824 infection in infants in the emergency de- diatrics. Clinical and demographic factors
15. Brilha S, Proença H, Cristino JM, Hänscheid partment: which test is best? Pediatrics. associated with urinary tract infection in
T. Use of flow cytometry (Sysmex) UF-100) 1998;101(6). Available at: www.pediatrics. young febrile infants. Pediatrics. 2005;116(3):
to screen for positive urine cultures: in org/cgi/content/full/101/6/e1 644–648
search for the ideal cut-off. Clin Chem Lab 27. Lammers RL, Gibson S, Kovacs D, Sears W, 37. Hewitt IK, Zucchetta P, Rigon L, et al. Early
Med. 2010;48(2):289–292 Strachan G. Comparison of test character- treatment of acute pyelonephritis in chil-
16. De Rosa R, Grosso S, Bruschetta G, et al. istics of urine dipstick and urinalysis at dren fails to reduce renal scarring: data
Evaluation of the Sysmex UF1000i flow various test cutoff points. Ann Emerg Med. from the Italian Renal Infection Study Trials.
cytometer for ruling out bacterial urinary 2001;38(5):505–512 Pediatrics. 2008;122(3):486–490
tract infection. Clin Chim Acta. 2010;411 28. Goldsmith BM, Campos JM. Comparison of 38. Pecile P, Miorin E, Romanello C, et al. Age-
(15–16):1137–1142 urine dipstick, microscopy, and culture for related renal parenchymal lesions in children
17. Lunn A, Holden S, Boswell T, Watson AR. the detection of bacteriuria in children. with first febrile urinary tract infections.
Automated microscopy, dipsticks and the Clin Pediatr (Phila). 1990;29(4):214–218 Pediatrics. 2009;124(1):23–29

PEDIATRICS Volume 134, Number 3, September 2014 529


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Automated Urinalysis and Urine Dipstick in the Emergency Evaluation of Young
Febrile Children
John T. Kanegaye, Jennifer M. Jacob and Denise Malicki
Pediatrics 2014;134;523
DOI: 10.1542/peds.2013-4222 originally published online August 18, 2014;

Updated Information & including high resolution figures, can be found at:
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Automated Urinalysis and Urine Dipstick in the Emergency Evaluation of Young
Febrile Children
John T. Kanegaye, Jennifer M. Jacob and Denise Malicki
Pediatrics 2014;134;523
DOI: 10.1542/peds.2013-4222 originally published online August 18, 2014;

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/134/3/523

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