TEXAS CHILDREN'S HOSPITAL DATE 5/2008

EVIDENCE-BASED CLINICAL DECISION SUPPORT

FIRST FEBRILE URINARY TRACT INFECTION CLINICAL GUIDELINE
Definition The presence of a pure growth of more than 105
colony forming units of bacteria per milliliter of urine. Lower
counts of bacteria may be clinically important, especially in
boys, and in specimens obtained by urinary catheter. Any
growth of typical urinary pathogens is considered clinically
important if obtained by suprapubic aspiration. (1)
Toxic appearance-irritable, disinterested in feeding,
lethargic, poor tone (floppy), fever, poor perfusion,
sluggish capillary refill, tachycardia or bradycardia,
tachypnea or apnea, sunken fontanelle, dry mucous
membranes, jaundice, vomiting

Pathophysiology The disease is usually caused by a bacterial In older children observe for fever suprapubic tenderness
infection. Escherichia coli is the most common bacterial and abdominal/flank tenderness
species identified. Other common gram negative species Laboratory
include Klebsiella, Proteus, Enterobacter and Citrobacter. Urinalysis or office dipstick positive for nitrites
Gram positive species include Staphylococcus saprophyticus and leukocyte esterase (LE) and/or positive microscopy(4)
and Enterococcus. Pyelonephritis results from bacterial
infection of the kidney. Sensitivity and Specificity of urinalysis components (2, 5-7)
Differential Diagnosis Consider empiric treatment until culture results are available
Renal abscess Discitis Sensitivity Specificity *LR+ * LR -
Kidney stones Trauma Dipstick (5) 70% 98% 35 0.3
Sacroiliitis Fever Dipstick & Micro 80% 64% 2.2 0.3
Vertebral osteomyelitis Gastroenteritis
Dipstick & Micro(6)
Appendicitis Vaginitis/urethritis 0-1 month old 82% 92% 10 0.2
>1-3 months 82% 94% 13 0.07
Guideline Eligibility Criteria (2, 3)
Age 2 months 12 years Bag LE (7) 76% 84% 4.75 0.29
Prepubertal children Cath LE 86% 94% 14 0.15
First episode of UTI Bag & Cath 84% 91% 9 0.17
Febrile **If nitrites are positive, diagnosis of UTI is very likely.

Guideline Exclusion Criteria (3) Positive Urine Culture (2-3)

Afebrile
Conditions in which immunity may be compromised such as: Suprapubic Aspiration (SPA) >1,000 cfu/ml
Transplant recipient (solid organ or hematopoetic)
Chronic renal insufficiency/kidney disease Cath Specimen >10,000 cfu/ml
Known major genitourinary anomalies
Sepsis with shock or meningitis High quality midstream clean >100,000 cfu/ml
ICU admission catch
Other severe comorbid conditions
Critical Points of Evidence(See page 9)
Diagnotic Evaluation Clinical history and physical
examination and labs are used to diagnose urinary tract
Evidence Supports
Oral antibiotic management (2, 3, 8-11)
infection (UTI):
Short courses (3-4 days) of IVantibiotics followed by oral
antibiotics are as effective as longer IV antibiotic courses
History Assess for
(7-14 days) (9,12)
Urinary symptoms (incontinence, lack of proper stream,
Midstream clean catch as method of choice to obtain urine
withholding maneuvers, frequency, urgency, dysuria)
specimen for toilet trained children (13)
Previous UTIs
LE and nitrite dipstick testing for rapid diagnosis of UTI (4)
Vesicoureteral reflux (VUR)
Obtained by non-invasive method. If + invasive method may be necessary
Previous undiagnosed febrile illnesses
Evidence Against
Family history of frequent UTIs, VUR and other
None
genitourinary abnormalities
Evidence Lacking
Constipation
Routine prophylactic antibiotic use (14,15)
Usefulness of imaging studies(22)
Physical Examination
In infants observe for fever, vomiting, diarrhea, lethargy, *LR+: a positive test increases the odds of disease by this factor
irritability, poor feeding, jaundice, and failure to thrive LR-: a negative test decreases the odds of disease by this factor
It is the odds that change not the probability.

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 Principles of Clinical Management Inpatient Discharge Criteria
A decreasing trend in daily maximal temperatures combined
Urine Specimen for Urinalysis and Culture*
with physician discretion
Non-toilet trained children: transuretheral catheterization(16,17)
On culture specific antibiotics
Toilet trained children: midstream clean catch (13, 18)
*Obtained by non-invasive method. If + invasive method may be necessary Tolerating oral intake
Hydration Patient/Caregiver discharge teaching completed on:
IV fluids if not taking oral fluids adequately Discharge care
Signs and symptoms of concern
Imaging Studies (19-22) Risk of recurrence
Proper perineal care
Children Females 2-6 years Documentation of scheduled PCP follow-up
2-24 months Males 2-12 years
Renal Ultrasound RUS
(RUS)(3,20) If RUS + OR the following risk Outcome Measures Outpatient
and factors exist order VCUG*: EC visit within 14 days for same problem
Voiding o Sibling with reflux EC visit within 14 days resulting in the admission for same
Cystourethrogram* o Decreased renal function problem
(VCUG) o Proteinuria Documented use of prophylactic antibiotics
o Hypertension
Females 6-12 years Outcome Measures Inpatient
RUS at discretion of physician based upon clinical Length of stay
findings EC visit within 14 days for same problem
Readmission within 14 days for same problem
NOTE: Obtain Renal Cortical Scan (DMSA) if identification Frequency of completed radiologic studies
of reflux or renal scarring will change management. (17, 20-22) Location of radiologic studies (inpatient or outpatient setting)
Time frame to complete radiologic studies
*VCUG may be performed as soon as fever is decreasing and Use of prophylactic antibiotics with documented reflux
culture specific antibiotics are in use. There is no need to Resistance pattern of organisms
perform an additional urinalysis if the patient is on appropriate
antibiotics.

Admission Criteria
Unable to tolerate oral fluids (requires IV fluids for hydration)
Failed outpatient therapy (requires IV antibiotics)
Toxic appearance

Parent Teaching
Parents should be taught how to recognize symptoms of UTI
Clearly explain the course of necessary testing and treatment
Explain strategies to prevent future recurrence (adequate
hydration, frequent voiding, perineal hygiene, completion of
antibiotic course)
Pediatrician follow up

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Antibiotic Therapy (2,3,8-11,14,23-25,27)
Consider insurance/Medicaid formulary restrictions

Empirical Oral Therapy-Outpatient

Age & Weight Parameters Dose and Frequency
Cefixime Infants and children 8 mg/kg/day divided every 12-24 hours; MAX: 400mg/day
CefPODoxime Proxetil Children > 2 months to 12 10 mg/kg/day divided every 12 hours; MAX: 800 mg/day
years
Empirical Parenteral Therapy (IV/IM)-Emergency Center or Inpatient
Age & Weight Parameters Dose and Frequency
CefOTAXime Sodium Infants > 2 months 50-75 mg/kg/dose every 8 hours; MAX: 2,000 mg/dose
Children 1-12 years (<50 kg)
Children 50 kg 1,000-2,000 mg/dose every 8 hours; MAX: 2,000 mg/dose
Ceftriaxone Soduim Infants and children 50 mg/kg/day divided every 24 hours
(EC only) MAX: 50 mg/kg/dose OR 2,000 mg/dose OR 4,000mg/day
Gentamicin Sulfate* Infants and children 2.5 mg/kg/dose divided every 8 hours
*Not typically first line MAX: 3 mg/kg/dose not to exceed 120 mg/dose
monotherapy
Directed Oral Therapy (Based on lab results)
Age & Weight Parameters Dose and Frequency
Cefixime Infants and children 8 mg/kg/day divided every 12-24 hours; MAX: 400 mg/day
CefPODoxime Proxetil Children > 2 months to 12 10 mg/kg/day divided every 12 hours; MAX: 800 mg/day
years
Amoxicillin Infants and children 40 mg/kg/day divided every 8 hours; MAX: 500mg/dose
Trimethoprim (TMP) and Children > 2 months 6-10 mg TMP/kg/day divided every 12 hours; MAX:
Sulfamethoxazole (SMX) 160mg/dose
Nitrofurantoin Children > 2 month to 12 5-7 mg/kg/day divided every 6 hours
years MAX: 400 mg/day
Directed Parenteral Therapy (IV)-Inpatient (Based on lab results)
Age & Weight Parameters Dose and Frequency
CefOTAXime Sodium Infants > 2 months 50-75 mg/kg/dose every 8 hours; MAX: 2,000 mg/dose
Children 1-12 years (<50 kg)
Children 50 kg 1,000-2,000 mg/dose every 8 hours; MAX: 2,000mg/dose
Ampicillin Infants and children 50 mg/kg/dose every 6 hours; MAX: 100 mg/kg/dose not
to exceed 2,000 mg/dose or 12,000 mg/day
Gentamicin Sulfate Infants and children 2.5 mg/kg/dose every 8 hours; MAX: 3 mg/kg/dose not to
exceed 120 mg/dose
Antibiotic Prophylaxis
Age & Weight Parameters Dose and Frequency
Trimethoprim (TMP) and Children > 2 months 2-4 mg TMP/kg/day once daily; MAX: 160mg/dose
Sulfamethoxazole (SMX)
Nitrofurantoin Children > 2 month to 12 1-2 mg/kg/day once daily; MAX: 100 mg/day
years

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 References
1. Larcombe J. (1999). Urinary tract infection in children. BMJ, 319(7218), 1173-1175.

2. American Academy of Pediatrics. (1999). Practice parameter: the diagnosis, treatment, and evaluation of the initial
urinary tract infection in febrile infants and young children. American Academy of Pediatrics. Committee on
Quality Improvement. Subcommittee on Urinary Tract Infection. Pediatrics, 103(4 Pt 1), 843-852.

3. Cincinnati Childrens Hospital Medical Center, Health Policy and Clinical Effectiveness Program, Evidence-Based
Care Guideline for children 12 years of age or less with First Urinary Tract Infection (2006), retreived August
2007, from http://www.cincinnatichildrens.org/NR/rdonlyres/215EED75-1BF7-47A9-B27A-
E01081ACC29C/0/utiguideline.pdf

4. Novak R, Powell K, & Christopher N. (2004). Optimal diagnostic testing for urinary tract infection in young children.
Pediatric and Developmental Pathology, 7, 226-230.

5. Armengol, CE, Hendley, J & Schlager, TA. (2001). Should we abandon standard microscopy when screening for
urinary tract in fections in young children? Pedia Infect Dis, 20(12), 1176-1177.

6. Bachur, R and Harper MB. (2001). Reliabitlity of the urinalysis for predicting urinary tract infections in young febrile
children. Arch Pediatr Adolesc Med, 155, 60-65.

7. Whiting P, Westwood, M, Watt I, Cooper J & Kleijnen J. (2005). Rapid tests and urine sampling techniques for the
diagnosis of urinary tract infection (UTI) in children under five years: A systematic review. BMC Pediatrics 5(4),
retrieved February 2008, from http://www.biomedcentral.com/1471-2431/5/4

8. Hodson EM, Willis NS, Craig JC. Antibiotics for acute pyelonephritis in children. Cochrane Database of Systematic
Reviews 2007, Issue 4. Art. No.: CD003772. DOI: 10.1002/14651858.CD003772.pub3.

9. Michael M, Hodson EM, Craig JC, Martin S, Moyer VA. Short versus standard duration oral antibiotic therapy for acute
urinary tract infection in children. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD003966.
DOI: 10.1002/14651858.CD003966.

10. Montini G, Toffolo A, Zucchetta P, Dall'Amico R, Gobber D, Calderan A, et al. (2007). Antibiotic treatment for
pyelonephritis in children: multicentre randomised controlled non-inferiority trial. BMJ, 335(7616), 386.

11. Pohl, A. Modes of administration of antibiotics for symptomatic severe urinary tract infections. Cochrane Database of
Systematic Reviews 2007, Issue 4. Art. No.: CD003237. DOI: 10.1002/14651858.CD003237.pub2.

12. Gauthier M, Chevalier I, Sterescu A, Bergeron S, Brunet S, & Taddeo D. (2004). Treatment of urinary tract infections
among febrile young children with daily intravenous antibiotic therapy at a day treatment center. Pediatrics,
114(4), e469-e476.

13. Schroeder AR, Newman TB, Wasserman RC, Finch SA, & Pantell RH. (2005). Choice of urine collection methods for
the diagnosis of urinary tract infection in young, febrile infants. Arch Pediatr Adolesc Med, 159(10), 915-922.

14. Conway PH, Cnaan A, Zaoutis T, Henry BV, Grundmeier RW, & Keren R. (2007). Recurrent urinary tract infections in
children: risk factors and association with prophylactic antimicrobials. JAMA, 298(2), 179-186.

15. Lutter SA, Currie ML, Mitz LB, & Greenbaum LA. (2005). Antibiotic resistance patterns in children hospitalized for
urinary tract infections. Arch Pediatr Adolesc Med, 159(10), 924-928.

16. McGillivray D, Mok E, Mulrooney E, & Kramer MS. (2005). A head-to-head comparison: "clean-void" bag versus
catheter urinalysis in the diagnosis of urinary tract infection in young children. J Pediatr, 147(4), 451-456.

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17. Garin EH, Olavarria F, Araya C, Broussain M, Barrera C, & Young L. (2007). Diagnostic significance of clinical and
laboratory findings to localize site of urinary infection. Pediatr Nephrol, 22(7), 1002-1006.

18. Vaillancourt S, McGillivray D, Zhang X, & Kramer MS. (2007). To clean or not to clean: effect on contamination rates
in midstream urine collections in toilet-trained children. Pediatrics, 119(6), e1288-1293.

19. Moorthy I, Easty M, McHugh K, Ridout D, Biassoni L, & Gordon I. (2005). The presence of vesicoureteric reflux does
not identify a population at risk for renal scarring following a first urinary tract infection. Arch Dis Child, 90, 733-
736.

20. Moorthy I, Wheat D, & Gordon I. (2004). Ultrasonography in the evaluation of renal scarring using DMSA scan as the
gold standard. Pediatric Nephrology, 19, 153-156.

21. Preda I, Jodal U, Sixt R, Stokland E & Hansson, S (2007). Normal dimercaptosuccinic acid scintigraphy makes
voiding cystourethrography unnecesssary after urinary tract infection. J Pediatr 151(6), 581-584.

22. Westwood ME, Whiting PF, Cooper J, Watt IS & Kleijnen J. (2005). Further investigation of confirmed urinary tract
infection (UTI) in children under five years: A systematic review. BMC Pediatrics 5(2), retrieved November 2007,
from http://www.biomedcentral.com/1471-2431/5/2

23. Prelog, M, et al. 2007. Febrile urinary tract infection in children: Ampicillin and trimethoprim insufficient as empirical
mono-therapy. Pediatr Nephrol. DOI 10.1007/s00467-007-0701-1.

24. Gaspari RJ, Dickson, E, Karlowsky, J, & Doern, G. (2006). Multidrug resistance in pediatric urinary tract infections.
Microbial Drug Resistance, 12(2), 126-129.

25. Williams GJ, Wei L, Lee A, Craig JC. Long-term antibiotics for preventing recurrent urinary tract infection in children.
Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD001534. DOI:
10.1002/14651858.CD001534.pub2.

26. National Institute for Clinical Excellence. Urinary tract infection in children: diagnoses, treatment and long-term
management. Clinical Guideline 54. London: NICE, 2007.
http://guidance.nice.org.uk/CG54/niceguidance/pdf/English/download.dspx (accessed August 2007)

27. Texas Children's Hospital Drug Information and Formulary. 9th ed. Hudson (OH): Lexi-Comp; 2007

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 Guideline Preparation
This guideline was prepared by the Evidence-Based (EB) Clinical
Decision Support Team in collaboration with content experts at
Texas Childrens Hospital. Development of this guideline supports
the TCH Quality and Patient Safety Program initiative to promote
clinical guidelines and outcomes that build a culture of quality and
safety within the organization.
Urinary Tract Infection Content Expert Team
Eric Jones, MD, Urology
Debra Palazzi, MD, Infectious Disease
Veronica Goytia, MD, Infectious Disease Fellow
Andrea Cruz, MD, Emergency Medicine Fellow
Bruce Parker, MD, Radiology
Stuart Goldstein, MD, Nephrology
Geeta Singhal, MD, FIS
Janet Pate, MD, TCPA Community Physician
Shelly Oh, Pharm.D.
Suzzette Wiener, RN
Margaret Anderson, MS, RD, LD, Nutrition
Lindsey Gregg, LMSW, Social Work
Diana Schaumburg, RN, CPHQ, Quality Outcomes Management
EB Clinical Decision Support Team
Ashley Breland, MSN, RN, CCRN, Research Specialist
Marilyn Hockenberry PhD, RN, PNP-CS, FAAN Co-Chair
Virginia Moyer MD, MPH Co-Chair
Development Process________________
This guideline was developed using the process outlined in the EB
Clinical Decision Support Manual (2007). The review summary
documents the following steps:
1. Review Preparation
-PICO questions established
-Evidence search confirmed with content experts
2. Review of Existing Internal and External Guidelines
- One published guideline from the AAP, from a childrens
hospitals and one from the United Kingdom were used
3. Literature Review of Relevant Evidence
-Searched: Medline, Cochrane, AHRQ, Cinahl, Trip, Best
BETS, AAP, PedsCCM, BMJ Clinical Evidence,
UpToDate, Google Scholar
4. Critically Analyze the Evidence
-One systematic review that included 50 articles, AAP
Guideline, Cincinnati Guideline, National Institute for
Health and Clinical Excellence Guideline, 10 RCTs in the
Cochrane Review-Short versus standard antibiotic therapy,
six RCTs in the Cochrane Review-Long-term Antibiotics
for Preventing Recurrent Urinary Tract Infection in
Children. 18 RCTs in the Cochrane Review-Antibiotics for
Acute Pyelonephritis in Children; two cohort studies, one
RCT, one quasi-experimental study
5. Summarize the Evidence by preparing the guideline, order sets
and interdisciplinary plan of care
-Materials used in the development of the guidelines, review
summaries and content expert team meeting minutes are
maintained in a urinary tract infection EB review manual
with the Center for Quality.
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Evaluating the Quality of the Evidence
The Critical Appraisal Skills Program (CASP) criteria were used
to evaluate the quality of articles reviewed. Application of the CASP
criteria are completed by rating each reviewed study or review as:
Strong study/systematic review - well designed, well conducted,
adequate sample size, reliable measures, valid results, appropriate
analysis, and clinically applicable/relevant.
Study/systematic review with minor limitations - specifically
lacking in one of the above criteria
Study/systematic review with major limitations - specifically
lacking in several of the above criteria.
Published clinical guidelines evaluated for this review using the
AGREE criteria. The summary of these guidelines are found at the
end of this document. AGREE criteria uses a 1-4 point likert scale
to evaluate 23 questions evaluating: Guideline Scope and Purpose,
Stakeholder Involvement, Rigor of Development, Clarity and
Presentation, Applicability, and Editorial Independence. The higher
the score the more comprehensive the guideline.
This guideline specifically summarizes the evidence in support of or
against specific interventions and identifies where evidence is
lacking. The following categories describe how research findings
provide support for treatment interventions.
Evidence that supports the guideline (p.1) provides clear evidence
from more than one well-done randomized controlled trial (RCT)
(based on CASP criteria) that the benefits of the intervention exceed
harm.
Evidence against (p.1) provides clear evidence from more than
one well-done RCT (based on CASP criteria) that the intervention is
likely to be ineffective or that it is harmful.
Evidence lacking (p.1) indicates there is currently insufficient data
or inadequate data to recommend for or against specific intervention.
Recommendations
Recommendations for the guidelines were developed by a consensus
process directed by the existing evidence, content experts and patient
and family preference when possible. The Content Expert Team and
EB Clinical Decision Support Team remain aware of the
controversies in the management of first urinary tract infection in
young patients. When evidence is lacking, options in care are
provided in the guideline and the order sets that accompany the
guideline.
Approval Process
Guidelines are reviewed and approved by the Content Expert Team,
EB Clinical Decision Support Team, EB Executive Steering Team,
Pharmacy and Therapeutics Committee and other appropriate
hospital committees as deemed appropriate for the guidelines
intended use. Guidelines are reviewed and updated as necessary
every 2 years within the EB Clinical Decision Support Team at Texas
Childrens Hospital. Content Expert Teams will be involved with
every review and update.
Disclaimer
Guideline recommendations are made from the best evidence, expert
opinions and consideration for the patients and families cared for
within TCH/TCPA. The guideline is NOT intended to impose
standards of care preventing selective variation in practice that are
necessary to meet the unique needs of individual patients. The
physician must consider each patients circumstance to make the
ultimate judgment regarding best care.
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