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

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Joseph B. Cantey1#, Claudia Gaviria-Agudelo1, Erin McElvania TeKippe1,2, Christopher D.

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Doern1,2

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Departments of 1Pediatrics and 2Pathology, University of Texas Southwestern Medical Center,

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Dallas, TX and Children’s Medical Center Dallas, Dallas, TX

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Running title: Urine Gram Stain for Diagnosis of Pediatric UTI

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#Corresponding Author:

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Joseph B. Cantey

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Department of Pediatrics

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University of Texas Southwestern Medical Center

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5323 Harry Hines Blvd

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Dallas, TX 75390

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Email: [email protected]

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Current affiliation for Claudia Gaviria-Agudelo: Valley Head Clinic, Scottsboro AL

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Current affiliation for Christopher Doern: Department of Pathology, Virginia Commonwealth

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University Medical Center, Richmond, VA

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Abstract

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Urinary tract infection (UTI) is one of the most common infections in children. Urine

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culture remains the gold standard for diagnosis, but the utility of urine Gram stain relative to

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urinalysis (UA) is unclear. We reviewed 312 pediatric patients with suspected UTI who had

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urine culture, UA, and urine Gram stain performed from a single urine specimen. UA was

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considered positive if ≥ 10 leukocytes per oil immersion field were seen or if either nitrates or

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leukocyte esterase testing was positive. Urine Gram stain was considered positive if any

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organisms were seen. Sensitivity, specificity, and positive and negative predictive value were

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calculated using urine culture as the gold standard. Thirty-seven (12%) patients had a culture-

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proven UTI. Compared to urine Gram stain, UA had equal sensitivity (97.3% vs. 97.5%) and

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higher specificity (85% vs 74%). Empiric therapy was prescribed before the Gram stain result

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was known in 40 (49%) patients and after in 42 (51%) patients. The antibiotics chosen did not

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differ between these two groups (p=0.81), nor did they differ for patients with Gram-negative

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rods on urine Gram stain compared to those with Gram-positive cocci (p=0.67). From this data

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we conclude that UA has excellent negative predictive value that is not enhanced by urine Gram

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stain and antibiotic selection did not vary based on the urine Gram stain result. In conclusion, the

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clinical utility of urine Gram staining does not warrant the time or cost it requires.

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Introduction

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Urinary tract infection (UTI) is one of the most common infections in children,

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accounting for up to 2% of pediatric hospital admissions at an annual cost of more than half a

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billion dollars (1). Timely diagnosis and antibiotic therapy is necessary to reduce the risk of

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serious complications from UTI (2). However, due to nonspecific manifestations, UTI requires a

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high degree of suspicion which in turn has contributed to both under- and over-diagnosis (3, 4).

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The need for timely antibiotic therapy necessitates the use of rapid diagnostic tests in addition to

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urine culture, notably urinalysis (UA) and urine Gram staining. However, the utility of urine

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Gram staining relative to UA remains controversial. Previous studies have supported the use of

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urine Gram staining, urinalysis, or both as a screening test (5-8). However, the most recent

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American Academy of Pediatrics guidelines for the management of UTI in children 2-24 months

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of age does not include Gram staining as part of the diagnosis (9). Furthermore, significant

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resources are required to perform urine Gram staining in a timely manner, including

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microbiology technician time. The objectives of our study were to identify the sensitivity and

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specificity of UA and urine Gram staining, and to determine whether urine Gram staining has

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utility in diagnosis or optimal antimicrobial prescribing for pediatric UTI.

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Materials and Methods

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Patient Cohort. We retrospectively included all patients aged ≤19 years of age who had a urine

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culture, urinalysis, and urine Gram stain ordered on a single urine specimen between September

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28 and November 19, 2011 at Children’s Medical Center, Dallas, Texas. Immunocompromised

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patients, including patients with malignancy undergoing chemotherapy, were excluded. Patients

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with structural or functional urologic defects requiring routine catheterization were also

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excluded.

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Patient Data Collection. Medical records were reviewed for pertinent demographic, clinical,

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and laboratory information and, specifically, the time from urine collection to reporting of

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results. Data on diagnosis of UTI, any prescribed antimicrobial therapy and the time that those

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orders were placed in the computerized physician order entry system were recorded. Urine

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collection method was documented; our local practice recommends clean-catch urine samples for

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children older than 2 years of age or older and catheterized specimens for children younger than

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2 years of age. This study was approved by the University of Texas Southwestern Medical

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Center Institutional Review Board (#082011-059).

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Laboratory Testing. Urinalysis and automated microscopy were performed from unspun urine

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on the Iris iQ®ELITE™ urine chemistry system (Iris® Diagnostics Division, Chatsworth, CA).

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Urine culture was considered positive if ≥50,000 colony-forming units of a uropathogen were

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identified (9). UA was considered positive if ≥10 leukocytes per oil immersion field were seen,

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or if either nitrates or leukocyte esterase testing was positive. Gram stain was considered positive

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if any organisms were seen. Urine culture results were used as the gold standard for comparison.

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Statistical Methods. Sensitivity, specificity, and positive and negative predictive value (PPV

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and NPV) were calculated for each testing method. Demographic variables were summarized

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using descriptive statistics. Comparisons between the categorical variables were performed using

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a chi-square or Fisher’s exact test, as appropriate. Paired continuous variables were compared

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with paired t test (normally distributed) or McNemar teste of paired proportions (if not normally

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distributed). The data were analyzed using SigmaPlot statistical software, version 12.5 (Systat

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Software, San Jose, CA).

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Results Three hundred and twelve patients had urine culture, UA, and urine Gram stain

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performed from a single urine specimen during the study period. Four patients had bag urine

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samples submitted and were excluded. Of the remaining 308 patients, 63% were female, and the

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median age was 4 years (interquartile range [IQR] 10 months – 10 years). All had their sample

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obtained in the out-patient setting, either through the emergency department (82%) or a clinic

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(18%). Urine samples were obtained by catheterization (55.2%) or clean-catch (44.8%). Thirty-

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seven patients (12%) had a pathogen identified in urine culture. Using urine culture as a gold

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standard for comparison, the sensitivity and specificity of UA and Gram staining were calculated

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(Table 1). The sensitivity and specificity of UA was 97.4% and 85.5%, and the PPV and NPV

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were 49.4% and 99.6%, respectively. Urine Gram stain had a sensitivity and specificity of

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97.3% and 73.8%, and the PPV and NPV were 33.6% and 99.5%. Of the 231 patients who had a

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negative UA, only eight had a positive Gram stain. There was no difference between the

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proportion of clean-catch (n=4) and catheterized (n=4) samples when comparing discordant UA

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and Gram stain results. All eight of these patients received antibiotics, but only one had a

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positive urine culture. Of the 199 patients with a negative Gram stain, 15 had a positive UA,

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seven received antibiotics, but only 1 had a positive urine culture.

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One hundred and thirty-seven (44%) patients were prescribed antibiotic therapy for

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presumptive UTI before the urine culture results were known. Empiric therapy was prescribed

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before any rapid urine test results were known in 55 (40%) patients, after the UA but before the

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Gram stain result in 40 (29%) patients and after the Gram stain results were known in 42 (31%).

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Patients who were prescribed antibiotics before any results were known were younger (median 2

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months [IQR 3 weeks – 4 months] versus 5 years [IQR 4 months – 10 years], p

Lack of clinical utility of urine gram stain for suspected urinary tract infection in pediatric patients.

Urinary tract infection (UTI) is one of the most common infections in children. Urine culture remains the gold standard for diagnosis, but the utility...
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