Professional Documents
Culture Documents
524 KANEGAYE et al
Downloaded from www.aappublications.org/news at Univ Of Virginia on November 4, 2019
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.
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.
526 KANEGAYE et al
Downloaded from www.aappublications.org/news at Univ Of Virginia on November 4, 2019
ARTICLE
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.
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
Updated Information & including high resolution figures, can be found at:
Services http://pediatrics.aappublications.org/content/134/3/523
References This article cites 36 articles, 14 of which you can access for free at:
http://pediatrics.aappublications.org/content/134/3/523#BIBL
Subspecialty Collections This article, along with others on similar topics, appears in the
following collection(s):
Emergency Medicine
http://www.aappublications.org/cgi/collection/emergency_medicine_
sub
Urology
http://www.aappublications.org/cgi/collection/urology_sub
Genitourinary Disorders
http://www.aappublications.org/cgi/collection/genitourinary_disorde
rs_sub
Permissions & Licensing Information about reproducing this article in parts (figures, tables) or
in its entirety can be found online at:
http://www.aappublications.org/site/misc/Permissions.xhtml
Reprints Information about ordering reprints can be found online:
http://www.aappublications.org/site/misc/reprints.xhtml
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
Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since 1948. Pediatrics is owned, published, and trademarked by
the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois,
60007. Copyright © 2014 by the American Academy of Pediatrics. All rights reserved. Print
ISSN: 1073-0397.