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Pediatrics 2014 Glissmeyer E1121 7
Pediatrics 2014 Glissmeyer E1121 7
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of ,10 000 CFUs per mL. Equivocal Statistical Analysis ity of dipstick for UTI was greater than
urine cultures were defined as growth Sensitivity, specificity, positive predictive combined urinalysis (93.8% [93.5%–
of urine pathogens with quantities be- value (PPV), and negative predictive value 94.1%] vs 87.6% [87.2%–88.0%]; P ,
tween 10 000 and 49 999 CFUs per mL. (NPV) were calculated for each of the .001) or microscopic urinalysis (93.8%
Subjects with equivocal results were urinalysis methods against the gold [93.5%–94.1%] vs 91.3% [90.9%–91.7%];
excluded from analysis. The signifi- standard of urine culture. Statistical cal- P , .001). The PPV of dipstick for UTI
cance determination for each culture culations were made by using the ROCR was also greater than combined uri-
was made by a clinical microbiologist package in R.13.1.23 To compare the nalysis (66.8% [66.2%–67.4%] vs 51.2%
(E.K.K.) and a pediatric infectious dis- performance characteristics between [50.6%–51.8%]; P , .001) or micro-
eases clinician (C.L.B.) and adjudicated methodologies, the z-statistic test for scopic urinalysis (66.8% [66.2%–67.4%]
by record review if required. Dipstick proportions was used. Dipstick urinalysis vs 58.6% [58.0%–59.2%]; P , .001). The
was considered positive if either leu- was compared with microscopic urinal- NPV was $98.6% for dipstick, micro-
kocyte esterase or nitrite was positive. ysis and with the combination of dipstick scopic, and combined urinalysis.
Microscopy was considered positive if and microscopic urinalysis. Comparisons Given differences in practice, infants
under high-power microscopic field were made for the entire cohort aged 1 aged 1 to 90 days were subdivided into
(HPF) the technician observed either to 90 days and 2 subgroups: infants aged those aged 1 to 28 days and those aged
.10 white blood cells (WBCs) or any 1 to 28 and those aged 29 to 90 days. 29 to 90 days. In infants 1 to 28 days old
bacteria. A positive combined urinaly- only, there was no difference in the NPV
sis was defined as any positive finding RESULTS of combined urinalysis and dipstick
for either dipstick or microscopy or (99.1% [95% CI: 98.9%–99.3%] vs 98.7%
both. Between July 1, 2004, and December 31,
[98.4%–99.0%]; P = .093). In infants 29
2011, we identified a total of 13 030 fe-
to 90 days old, the NPV of combined
Laboratory Methods brile infant encounters at Intermoun-
urinalysis was greater than dipstick
Leukocyte esterase and nitrite were tain Healthcare facilities (Fig 1). Of
(99.2% [99.1%–99.3%] vs 98.7% [98.5%–
these, 6536 (50%) had all urine studies
considered negative or positive including 98.9%]; P , .003). When analyzed by age,
any result $trace, as determined by including dipstick urinalysis, centri-
urinalysis tests in infants aged 29 to 90
colorimetric interpretation of the dip- fuged microscopic urinalysis, and
days had higher specificity and PPV
stick by a semiautomated urine chemis- urine culture performed. One hundred
compared with infants aged 1 to 28
try analyzer. Two methods of urine forty-two of 6536 infants (2%) had
days (Table 1). Dipstick sensitivity was
dipstick were used at the participating a urine culture meeting our definition
greater in infants aged 1 to 28 days
centers. A Siemens Multistix 8 SG dipstick of equivocal and were excluded from
(91.7%; 95% CI: 91.0%–92.4%) compared
interpreted on CLINITEK Advantus urine the primary analysis, leaving 6394 fe-
with infants aged 29 to 90 days (90.4%;
chemistry analyzer (Siemens Medical brile infants aged 1 to 90 days for
95% CI: 90.0%–90.8%). No differences by
Solutions USA, Inc., Malvern, PA) was analysis. Of the infants included in
age in urinalysis test performance were
used at the PCH. All other facilities used analysis, 770 of 6394 (12%) had a urine
seen for NPV (Table 1).
an Aution 9EB strip interpreted on Aution culture meeting our definition of posi-
AX-4280 urine chemistry analyzer (Iris tive for UTI and 5624 had negative urine
cultures. Of the 6394 infants, 1745 were Evaluation of Cases of
Diagnostics, Chatsworth, CA). Micro-
aged 1 to 28 days (27%) and 4649 were Culture-Confirmed UTI Not
scopic tests (WBCs and bacteria) were
29 to 90 days old (73%). Most subjects Identified by Dipstick
performed using uniform standardized
CLIA-certified methods on centrifuged (79%) were evaluated at PCH. Demographic and laboratory charac-
urine specimens. A total of 10 mL of urine teristics of cases of culture-confirmed
was centrifuged for 5 to 7 minutes at Performance Characteristics of UTI not identified by urine dipstick test-
a relative centrifugal force of 400 g, and Urine Screening Tests ing in infants 29 to 90 days old are shown
the technician averaged the findings of Performance characteristics of the in Table 2. Infants 1 to 28 days old were
least 10 unstained HPFs under the 403 urine screening tests are presented in excluded because most were admitted
objective. WBCs were considered positive Table 1. The sensitivity of combined for at least 24 hours and UTI not identi-
if the laboratory reported .10 WBCs per urinalysis for UTI was greater than for fied by dipstick could be identified by
HPF. Bacteria were considered negative dipstick (94.7% [95% confidence in- culture during hospitalization.
or positive including any $1 (rare) bac- terval (CI): 94.4%–95.0%] vs 90.8% Fifty-three infants aged 29 to 90 days had
teria per HPF. [90.4%–91.2%]; P , .001). The specific- UTI with normal dipstick testing. Twenty-
DISCUSSION
We report data from the largest study of
urinary diagnostic testing in febrile
infants aged 1 to 90 days. In our study,
dipstick performed well as a stand-
alone screening test to rule out UTI,
with an overall NPV of 98.7%. In cases in
which dipstick screening was negative
in infants later identified to have
culture-confirmed UTI, the mean time to
positive culture was 19.7 hours and no
FIGURE 1 adverse events related to delayed
Flow diagram of included infants. Urine tests included dipstick urinalysis, centrifuged microscopic treatment were documented. Although
urinalysis, and urine culture.
the addition of microscopy to dipstick
increased the NPV to 99.2%, the com-
seven of these screened positive by Prediction of Outcomes on the bined testing would be predicted to
urine microscopy, leaving 26 not iden- Basis of Test Performance cause additional false-positive results
tified by either screening method. Eighty- that might lead to unnecessary inter-
Given the UTI prevalence in a population
three percent (44 of 53) of these infants ventions, including hospital admission.
and screening test performance char-
were admitted on initial encounter and Urine dipstick test alone may be an
acteristics, we calculated the expected
most received antibiotic treatment ef- adequate screen for UTI in febrile
outcomes in a hypothetical cohort on the
fective against UTI. Nine of the 53 infants infants aged 1 to 90 days while awaiting
basis of institutional treatment para-
(17%) were not admitted to the hospital urine culture results.
digms.UTIprevalenceininfantsaged29to
at the time of initial evaluation. Positive 90 days was 11.9%. If 1000 febrile infants Urine dipstick compared favorably with
urine cultures were identified in all 9 of undergo testing for UTI, 119 would have urine microscopy and combined urinal-
these infants by 24 hours (mean: 19.7 culture-positive UTI and 881 would not. If ysis. On all measurements, dipstick was
hours).Sixofthese9infantshadfollow-up dipstick alone were used as a screen for equivalent or superior to microscopy.
and appropriate treatment documented UTI, 108 of 119 (90.4%) would screen Dipstick NPV is statistically inferior to
in the in the EDW of the Intermountain positive and 55 of 881 (6.2%; 1-specificity) combined urinalysis (98.7% [95% CI:
Healthcare system. would screen false positive for UTI. These 98.6%–98.8%] vs 99.2% [99.1%–99.3%];
Two of the 53 infants (3.8%) with normal infants would all be expected to receive P , .001), but this difference may not
dipstick testing had bacteremia with antibiotic treatment, and most would be be clinically significant. Dipstick has
the same organism causing UTI (Ta- admitted. If combined urinalysis were a superior PPV compared with com-
ble 2). Both were admitted to the hos- used, 113 of 119 (94.8%) would screen bined urinalysis (66.8% [66.2%–67.4%]
pital at the time of initial evaluation, positiveand96of881(10.9%;1-specificity) vs 51.2% [50.6%–51.8%]; P , .001).
one for poor feeding and irritability would screen false positive for UTI. The Dipstick testing does not require CLIA
and the other for a peripheral WBC addition of urine microscopy to dipstick certification and can be performed
count .15 000, which is one of the In- testing in 1000 febrile infants would be rapidly in a variety of care settings by
termountain EB-CPM high-risk criteria. predicted to correctly identify 5 additional personnel with minimal training. Our
None of the 53 infants had positive ce- UTIsandfalselypredictUTIin41additional data suggest that the use of dipstick
rebrospinal fluid cultures. There were infants when compared with dipstick without microscopy may be an effective
no adverse outcomes identified in these alone. Performing urine microscopy in screen and the use of dipstick alone
53 infants with subsequent identifica- this cohort would be expected to result in could reduce the time required and
tion of UTI after initial negative dipstick up to 8 febrile infants aged 29 to 90 days costs associated with the laboratory
screening. with a false-positive screen for UTI, and evaluation of febrile infants.
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ARTICLE
TABLE 1 Performance Characteristics and Comparisons of Dipstick to Microscopic and Combined Urinalysis
Performance Performance, % (95% CI) z-Statistic (P)
Characteristic
and Infant Age Group Dipstick Microscopic Combined Dipstick Versus Microscopic Dipstick Versus Combined
Urinalysis Urinalysis Urinalysis Urinalysis Urinalysis
Sensitivity
1–90 days 90.8 (90.4–91.2) 90.3 (89.9–90.7) 94.7 (94.4–95.0) 1.01 (.157) 9.19 (,.001)
1–28 days 91.7 (91.0–92.4) 90.7 (90.0–91.4) 94.4 (93.8–95.0) 0.15 (.441) 3.69 (,.001)
29–90 days 90.4 (90.0–90.8) 90.1 (89.7–90.5) 94.8 (94.5–95.1) 0.41 (.342) 9.01 (,.001)
Specificity
1–90 days 93.8 (93.5–94.1) 91.3 (90.9–91.7) 87.6 (87.2–88.0) 3.56 (,.001) 3.31 (,.001)
1–28 days 90.4 (89.7–91.1) 89.0 (88.3–89.7) 83.7 (82.8–84.6) 5.43 (,.001) 1.38 (.084)
29–90 days 95.1 (94.8–95.4) 92.1 (91.7–92.5) 89.1 (88.6–89.6) 6.63 (,.001) 2.82 (.002)
PPV
1–90 days 66.8 (66.2–67.4) 58.6 (58.0–59.2) 51.2 (50.6–51.8) 5.63 (,.001) 10.72 (,.001)
1–28 days 57.4 (56.2–58.6) 53.8 (52.6–55.0) 45.0 (43.8–46.2) 1.35 (.088) 4.66 (,.001)
29–90 days 71.4 (70.7–72.1) 60.8 (60.1–61.5) 54.1 (53.4–54.8) 6.22 (,.001) 10.14 (,.001)
NPV
1–90 days 98.7 (98.6–98.8) 98.6 (98.5–98.7) 99.2 (99.1–99.3) 0.01 (.497) 3.23 (.001)
1–28 days 98.7 (98.4–99.0) 98.6 (98.3–98.9) 99.1 (98.9–99.3) 0.01 (.498) 1.32 (.093)
29–90 days 98.7 (98.5–98.9) 98.6 (98.4–98.8) 99.2 (99.1–99.3) 0.01 (.498) 2.77 (.003)
N = 6394 for infants aged 1–90 days, n = 1745 for those aged 1–28 days, and n = 4649 for those aged 29–90 days.
Regardless of the UTI screening method Up to 8 febrile infants aged 29 to 90 days performed dipstick in this study is
used, a small number of UTIs in febrile would be predicted to have the addi- higher than previous estimates of 75%
infants aged 1 to 90 days will initially be tional health care utilization associated to 85%.9,16,26,27 However, these other
missed. Febrile infants in our study with with a false-positive UTI diagnosis for studies defined UTI at a lower thresh-
UTI and negative dipstick screening did every 1 infant with true UTI not identified old of $10 000 CFUs per mL and/or
not experience adverse outcomes. by dipstick at the time of initial evalu- emphasized infants and children older
Eighty-three percent of the infants aged ation. than 90 days.
29 to 90 days with UTI and false-negative No urine-screening test was completely Our study has several limitations. Data
dipstick were admitted on initial en- accurate in predicting UTI in our pop- analysis was retrospectively performed
counter. The infants who were dis- ulation. In addition, urine screening is from a data set collected for other
charged after the initial evaluation not the only factor used to guide the purposes.3 Patients without urine cul-
were given instructions for observation management of febrile infants. Clinical ture or for whom both urine dipstick
in the outpatient settings, decreasing appearance, other laboratory test and microscopy were not performed
the risk of unrecognized progression of results, health system, and social and were not included. Subjects with urine
their infection. The urine culture results geographic factors are also used in cultures considered indeterminate
were positive in ,24 hours, and infants determining the disposition of febrile were excluded from analysis. Our use
returned for additional evaluation and infants aged 29 to 90 days. Our data of centrifuged urine specimens for
treatment in most cases. The expected revealed that 83% of infants found to microscopy has been reported else-
rapid turnaround time for urine cul- have UTI after normal dipstick screen, where9 but differs from other methods16
tures offers the opportunity for close were admitted to the hospital at the time and does not include urine Gram-stain.28
follow-up and initiation of antimicro- of initial evaluation. Microscopy also Dipstick was performed in the clini-
bial therapy if indicated. adds additional cost to the evaluation of cal laboratory and automated colori-
The risk of failing to identify UTI at initial the febrile infant and may also increase metric interpretation was used. The
encounter should be balanced with length of stay in the emergency de- results may not be the same in point-
clinical risks to the patient and the partment while awaiting results. of-care settings using visual dipstick
potential increase in health care expen- Although our study population had interpretation. Although we excluded
ditures associated with incorrectly pre- a prevalence of UTI (12%) similar to subjects with bag urine–labeled speci-
dicting UTI when none exists. Our data populations from previous pub- mens, the limitations of the EDW did
suggest that false-positive screens for lications,5,24,25 there are some differ- not allow us to confirm all samples
UTI will be higher in febrile infants when ences in urinalysis test performance. obtained by urethral catheterization.
urine microscopy is routinely performed. The 90.8% sensitivity of laboratory- We assume very few, if any, specimens
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