JCM Accepted Manuscript Posted Online 4 February 2015 J. Clin. Microbiol. doi:10.1128/JCM.00045-15 Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Lack of clinical utility of urine Gram stain for suspected urinary tract infection in pediatric patients
1 2 3 4 5
Joseph B. Cantey1#, Claudia Gaviria-Agudelo1, Erin McElvania TeKippe1,2, Christopher D.
6
Doern1,2
7 8
Departments of 1Pediatrics and 2Pathology, University of Texas Southwestern Medical Center,
9
Dallas, TX and Children’s Medical Center Dallas, Dallas, TX
10 11
Running title: Urine Gram Stain for Diagnosis of Pediatric UTI
12 13
#Corresponding Author:
14
Joseph B. Cantey
15
Department of Pediatrics
16
University of Texas Southwestern Medical Center
17
5323 Harry Hines Blvd
18
Dallas, TX 75390
19
Email:
[email protected] 20 21
Current affiliation for Claudia Gaviria-Agudelo: Valley Head Clinic, Scottsboro AL
22
Current affiliation for Christopher Doern: Department of Pathology, Virginia Commonwealth
23
University Medical Center, Richmond, VA
24 25 1
26
Abstract
27
Urinary tract infection (UTI) is one of the most common infections in children. Urine
28
culture remains the gold standard for diagnosis, but the utility of urine Gram stain relative to
29
urinalysis (UA) is unclear. We reviewed 312 pediatric patients with suspected UTI who had
30
urine culture, UA, and urine Gram stain performed from a single urine specimen. UA was
31
considered positive if ≥ 10 leukocytes per oil immersion field were seen or if either nitrates or
32
leukocyte esterase testing was positive. Urine Gram stain was considered positive if any
33
organisms were seen. Sensitivity, specificity, and positive and negative predictive value were
34
calculated using urine culture as the gold standard. Thirty-seven (12%) patients had a culture-
35
proven UTI. Compared to urine Gram stain, UA had equal sensitivity (97.3% vs. 97.5%) and
36
higher specificity (85% vs 74%). Empiric therapy was prescribed before the Gram stain result
37
was known in 40 (49%) patients and after in 42 (51%) patients. The antibiotics chosen did not
38
differ between these two groups (p=0.81), nor did they differ for patients with Gram-negative
39
rods on urine Gram stain compared to those with Gram-positive cocci (p=0.67). From this data
40
we conclude that UA has excellent negative predictive value that is not enhanced by urine Gram
41
stain and antibiotic selection did not vary based on the urine Gram stain result. In conclusion, the
42
clinical utility of urine Gram staining does not warrant the time or cost it requires.
43 44 45 46
2
47
Introduction
48
Urinary tract infection (UTI) is one of the most common infections in children,
49
accounting for up to 2% of pediatric hospital admissions at an annual cost of more than half a
50
billion dollars (1). Timely diagnosis and antibiotic therapy is necessary to reduce the risk of
51
serious complications from UTI (2). However, due to nonspecific manifestations, UTI requires a
52
high degree of suspicion which in turn has contributed to both under- and over-diagnosis (3, 4).
53
The need for timely antibiotic therapy necessitates the use of rapid diagnostic tests in addition to
54
urine culture, notably urinalysis (UA) and urine Gram staining. However, the utility of urine
55
Gram staining relative to UA remains controversial. Previous studies have supported the use of
56
urine Gram staining, urinalysis, or both as a screening test (5-8). However, the most recent
57
American Academy of Pediatrics guidelines for the management of UTI in children 2-24 months
58
of age does not include Gram staining as part of the diagnosis (9). Furthermore, significant
59
resources are required to perform urine Gram staining in a timely manner, including
60
microbiology technician time. The objectives of our study were to identify the sensitivity and
61
specificity of UA and urine Gram staining, and to determine whether urine Gram staining has
62
utility in diagnosis or optimal antimicrobial prescribing for pediatric UTI.
63 64
Materials and Methods
65
Patient Cohort. We retrospectively included all patients aged ≤19 years of age who had a urine
66
culture, urinalysis, and urine Gram stain ordered on a single urine specimen between September
67
28 and November 19, 2011 at Children’s Medical Center, Dallas, Texas. Immunocompromised
68
patients, including patients with malignancy undergoing chemotherapy, were excluded. Patients
3
69
with structural or functional urologic defects requiring routine catheterization were also
70
excluded.
71
Patient Data Collection. Medical records were reviewed for pertinent demographic, clinical,
72
and laboratory information and, specifically, the time from urine collection to reporting of
73
results. Data on diagnosis of UTI, any prescribed antimicrobial therapy and the time that those
74
orders were placed in the computerized physician order entry system were recorded. Urine
75
collection method was documented; our local practice recommends clean-catch urine samples for
76
children older than 2 years of age or older and catheterized specimens for children younger than
77
2 years of age. This study was approved by the University of Texas Southwestern Medical
78
Center Institutional Review Board (#082011-059).
79 80
Laboratory Testing. Urinalysis and automated microscopy were performed from unspun urine
81
on the Iris iQ®ELITE™ urine chemistry system (Iris® Diagnostics Division, Chatsworth, CA).
82
Urine culture was considered positive if ≥50,000 colony-forming units of a uropathogen were
83
identified (9). UA was considered positive if ≥10 leukocytes per oil immersion field were seen,
84
or if either nitrates or leukocyte esterase testing was positive. Gram stain was considered positive
85
if any organisms were seen. Urine culture results were used as the gold standard for comparison.
86 87
Statistical Methods. Sensitivity, specificity, and positive and negative predictive value (PPV
88
and NPV) were calculated for each testing method. Demographic variables were summarized
89
using descriptive statistics. Comparisons between the categorical variables were performed using
90
a chi-square or Fisher’s exact test, as appropriate. Paired continuous variables were compared
91
with paired t test (normally distributed) or McNemar teste of paired proportions (if not normally
4
92
distributed). The data were analyzed using SigmaPlot statistical software, version 12.5 (Systat
93
Software, San Jose, CA).
94 95 96
Results Three hundred and twelve patients had urine culture, UA, and urine Gram stain
97
performed from a single urine specimen during the study period. Four patients had bag urine
98
samples submitted and were excluded. Of the remaining 308 patients, 63% were female, and the
99
median age was 4 years (interquartile range [IQR] 10 months – 10 years). All had their sample
100
obtained in the out-patient setting, either through the emergency department (82%) or a clinic
101
(18%). Urine samples were obtained by catheterization (55.2%) or clean-catch (44.8%). Thirty-
102
seven patients (12%) had a pathogen identified in urine culture. Using urine culture as a gold
103
standard for comparison, the sensitivity and specificity of UA and Gram staining were calculated
104
(Table 1). The sensitivity and specificity of UA was 97.4% and 85.5%, and the PPV and NPV
105
were 49.4% and 99.6%, respectively. Urine Gram stain had a sensitivity and specificity of
106
97.3% and 73.8%, and the PPV and NPV were 33.6% and 99.5%. Of the 231 patients who had a
107
negative UA, only eight had a positive Gram stain. There was no difference between the
108
proportion of clean-catch (n=4) and catheterized (n=4) samples when comparing discordant UA
109
and Gram stain results. All eight of these patients received antibiotics, but only one had a
110
positive urine culture. Of the 199 patients with a negative Gram stain, 15 had a positive UA,
111
seven received antibiotics, but only 1 had a positive urine culture.
112
One hundred and thirty-seven (44%) patients were prescribed antibiotic therapy for
113
presumptive UTI before the urine culture results were known. Empiric therapy was prescribed
114
before any rapid urine test results were known in 55 (40%) patients, after the UA but before the
5
115
Gram stain result in 40 (29%) patients and after the Gram stain results were known in 42 (31%).
116
Patients who were prescribed antibiotics before any results were known were younger (median 2
117
months [IQR 3 weeks – 4 months] versus 5 years [IQR 4 months – 10 years], p