Clinical Presentation & Indications for Testing

Urine Collection & Laboratory Testing

General Management Recommendations

Antibiotic Therapy

Imaging

• To improve the use of appropriate diagnostic criteria
• To improve the use of appropriate antibiotic therapy
• To improve the use of appropriate imaging studies
• To avoid long-term medical problems
• To improve parental involvement in decision-making around the management of UTIs
• To identify the infants and children at most risk for long-term renal damage

To assist urologists and physicians from other medical specialties in their daily practice

• United States
• Children 12 years of age or less, with a first presumed or definite episode of UTI

These guidelines are not intended for use in children:

• With known immunodeficiencies
• With known major genitourinary anomalies
• With sepsis with shock or meningitis
• Needing ventilator or other intensive care
• With other severe comorbid conditions

Children with UTIs

Advanced Practice Nurses
Allied Health Personnel
Health Care Providers
Nurses
Patients
Physician Assistants
Physicians

Physician Assistants
Physicians

• Searches of Electronic Databases

Described Process: To select evidence for critical appraisal by the group, the Medline, EmBase, and the Cochrane databases were searched for dates of January 1999 through October 2004 to generate an unrefined, "combined evidence" database using a search strategy focused on answering clinical questions relevant to UTI and employing a combination of Boolean searching on human-indexed thesaurus terms (Medical Subject Heading [MeSH] headings using an OVID Medline interface) and "natural language" searching on words in the title, abstract, and indexing terms. The citations were reduced by eliminating duplicates, review articles, non-English articles, and adult articles. The resulting abstracts were reviewed by a methodologist to eliminate low-quality and irrelevant citations. During the course of the guideline development, additional clinical questions were generated and subjected to the search process.

November 2006 Update

A search using the above criteria was conducted for dates of October, 2004 through July, 2006. One relevant article was selected as potentially requiring changes to the 2005 version of the recommendations. The article was appraised and the Team approved the changes to the guideline (see the "Development Process" section in the original guideline document for details).

Number of Source Documents:

669 (2005 version) plus 148 (2006 update)

Number of References: 70

• Hand Searches of Published Literature (Primary Sources)
• Searches of Electronic Databases

Described Process: For literature review, PubMed was searched for published meta-analyses, which were used as far as available. Otherwise there was a non-structured literature review process by the group members. Each member was responsible for one chapter (reporter).

Number of Source Documents:

Not stated

Number of References: 69

Not stated

Weighting According to a Rating Scheme (Scheme Given - Refer to Table 7)

• Review
• Review of Published Meta-Analyses

(Process not described)

• Review of Published Meta-Analyses
• Systematic Review

Described Process: The method currently in use ensures that nearly all randomized controlled trials and meta-analyses are included in the guidelines

Expert Consensus

Described Process:

The recommendations contained in this document were formulated by an interdisciplinary working group which performed systematic and critical literature reviews, using the grading scale described below under "Type of Evidence Supporting the Recommendations," and examined current local practices.

Recommendations have been formulated by a consensus process directed by best evidence, patient and family preference, and clinical expertise. During formulation of these guidelines, the team members have remained cognizant of controversies and disagreements over the management of these patients. They have tried to resolve controversial issues by consensus where possible and, when not possible, to offer optional approaches to care in the form of information that includes best supporting evidence of efficacy for alternative choices.

Expert Consensus (Consensus Development Conference)

Described Process: The members of the UTI Working Group of the European Association of Urologists (EAU) Health Care Office established the first version of these guidelines in several consensus conferences. The members of the current UTI Working Group of the EAU Guidelines Office updated the guidelines in several consensus conferences thereafter. The first draft of each chapter was sent to the committee members asking for comments, which were then considered, discussed and incorporated accordingly.

The formal agreement to each updated chapter was achieved by the European Association of Urology (EAU) working group at three plenary meetings: the first in Paris on 10 December 2004, the next in Istanbul on 15 March 2005, and finally in Florence on 22 October 2005. Each chapter was reviewed by three committee members (editorial group) for consistency and compatibility in two editorial meetings: one meeting took place in Straubing, 22-24 April 2005, and one in Stavern, 9-11 Sept 2005, and the chapters were revised accordingly.

• Sensitivity and specificity of laboratory testing (urinalysis)
• Identification of anatomic abnormalities
• Infection recurrence
• Long-term renal damage

• Sensitivity and specificity of diagnostic tests
• Side effects of treatment
• Recurrence rate
• Morbidity (renal damage) from UTIs
• Correction of association urological lesions

This guideline was developed without external funding. All Team Members and Clinical Effectiveness support staff listed have declared whether they have any conflict of interest and none were identified.

All members of the Management of Urinary and Male Genital Tract Infections guidelines writing panel have provided disclosure statements of all relationships which they have and which may be perceived as a potential source of conflict of interest. This information is kept on file in the European Association of Urology (EAU) Central Office database. This guidelines document was developed with the financial support of the EAU. The EAU is a non-profit organisation and funding is limited to administrative assistance, travel, and meeting expenses. No honoraria or other reimbursements have been provided.

Members identified; Affiliations provided; Multidisciplinary; Includes patient representation

Members identified

Cincinnati Children's Hospital Medical Center

European Association of Urology

Electronic and print distribution; Open access

Electronic copies: Available from the Cincinnati Children's Hospital Medical Center Web site.

For information regarding the full-text guideline, print copies, or evidence-based practice support services contact the Children's Hospital Medical Center Health Policy and Clinical Effectiveness Department at HPCEInfo@chmcc.org.

Electronic and print distribution; Open access

Electronic copies: Available in Portable Document Format (PDF) from the European Association of Urology Web site.

Print copies: Available from the European Association of Urology, PO Box 30016, NL-6803, AA ARNHEM, The Netherlands.

Chart Documentation/Checklists/Forms
Clinical Algorithm
Foreign Language Translations
Patient Resources
Quick Reference Guides/Physician Guides

Clinical Algorithm
Pocket Guide/Reference Cards

Assessment and Diagnosis

History and Physical Examination

It is recommended that prompt evaluation for a diagnosis of UTI be conducted. See Appendix 5 of the original guideline document (reproduced below) for clinical findings consistent with the diagnosis of a UTI.

Note: Risk factors for UTI include:

• Male
  • Uncircumcised < 1 year
  • All < 6 months
• Female, in general
  • Particularly < 1 year
• Non-African-American race
• Fever > 39° C

(Shaw 1998 [C], Craig 1996 [C], Hoberman 1993 [C], Bachur 2001a [D], Bachur 2001b [D]).

Absence of high fever or other specific risk factors does not preclude the presence of UTI. See Appendix 2 and Appendix 3 in the original guideline document.

Clinical Signs and Symptoms of UTI

Newborns

• Jaundice
• Sepsis
• Failure to thrive
• Vomiting
• Fever

Infants and Preschoolers

• Diarrhea
• Failure to thrive
• Vomiting
• Fever
• Strong-smelling urine
• Abdominal or flank pain
• New onset urinary incontinence
• Dysuria (preschoolers)
• Urgency (preschoolers)

School Age Children

• Vomiting
• Fever
• Strong-smelling urine
• Abdominal or flank pain
• New onset urinary incontinence
• Dysuria
• Urgency
• Frequency

Signs and Symptoms

Symptoms are non-specific, and vary with the age of the child and the severity of the disease. Epididymo-orchitis is extremely unusual. With scrotal pain and inflammation in a boy, testicular torsion has to be considered.

A UTI in neonates may be non-specific and with no localization. In small children, a UTI may present with gastrointestinal signs, such as vomiting and diarrhoea. In the first weeks of life, 13.6% of patients with fever have a UTI. Rarely, septic shock will be the presentation. Signs of a UTI may be vague in small children, but later on, when they are older than 2 years, frequent voiding, dysuria and suprapubic, abdominal or lumbar pain may appear with or without fever.

Classification

UTIs may be classified either as a first episode or recurrent, or according to severity (simple or severe).

Recurrent UTI may be subclassified into three groups:

• Unresolved infection: subtherapeutic level of antimicrobial, non-compliance with treatment, malabsorption, resistant pathogens.
• Bacterial persistence: may be due to a nidus for persistent infection in the urinary tract. Surgical correction or medical treatment for urinary dysfunction may be needed.
• Reinfection: each episode is a new infection acquired from periurethral, perineal or rectal flora.

From the clinical point of view, severe and simple forms of UTIs should be differentiated because to some extent the severity of symptoms dictates the degree of urgency with which investigation and treatment are to be undertaken.

Severe UTI

• Fever >39°C
• Persistent vomiting
• Serious dehydration
• Poor treatment compliance

Severe UTI is related to the presence of fever of > 39°C, the feeling of being ill, persistent vomiting, and moderate or severe dehydration.

Simple UTI

• Mild pyrexia
• Good fluid intake
• Slight dehydration
• Good treatment compliance

A child with a simple UTI may have only mild pyrexia, but is able to take fluids and oral medication. The child is only slightly or not dehydrated and has a good expected level of compliance. When a low level of compliance is expected, such a child should be managed as one with a severe UTI.

Diagnosis

Physical Examination

It is mandatory to look for phimosis, labial adhesion, signs of pyelonephritis, epididymo-orchitis, and stigmata of spina bifida, e.g., hairy patch on the sacral skin. The absence of fever does not exclude the presence of an infective process.

Laboratory Studies

• It is recommended that urine samples be collected by catheter or SPA (if age-appropriate), if a high quality CCM urine sample cannot be obtained (Hoberman 1996 [C], Weinberg 1991 [D]).

  Note 1: In a child with a low clinical suspicion of UTI, and in whom a catheterization would be both required for a culture and considered invasive by the clinician or the family, the option to perform a dipstick or routine urinalysis on a specimen collected by more convenient means may be considered, followed by catheterization if the urinalysis suggests a UTI (AAP 1999 [S]). See Table 1 in the original guideline document.

  Note 2: See CCHMC Nursing Policies, Procedures and Standards: "III-701 Urinary Catheterization/Bladder Irrigation" in the "Availability of Companion Documents" field.

• It is recommended, in screening for UTI, to perform:
  • Dipstick (nitrite and LE) or
  • Routine urinalysis (nitrite, LE and microscopy)

    And

  • Urine culture and susceptibilities (Gorelick 1999 [M]). See Table 1 in the original guideline document.

  Note: Gram stain is not commonly conducted in the Cincinnati pediatric community (Hoberman 1996 [C]).

Diagnosis

General

Presumed UTI is diagnosed while urine culture results are pending in a child with abnormal laboratory studies and clinical findings consistent with the diagnosis of a UTI.

Definite UTI is diagnosed after obtaining a positive result for a urine culture in a child presenting with a clinical profile consistent with a UTI.

Presumed UTI

It is recommended that while pending results of culture, any positive result from a dipstick or routine urinalysis, in the presence of clinical findings consistent with the diagnosis of a UTI, be considered consistent with a presumptive diagnosis of UTI (Gorelick 1999 [M]).

Any one of the following study results defines a positive urinalysis (Gorelick 1999 [M]). See Table 1 and Table 2 in the original guideline document.

• Positive nitrite screen
• Positive LE
• Positive microscopic exam: the definition of abnormal microscopic exam is dependent on patient or provider-specific determinants

Definite UTI

It is recommended that a definite UTI be defined as a single organism cultured from a SPA, catheter specimen, or CCM specimen at the following concentrations. The higher the concentration of organisms, the more reliable the results; however, colony counts must be interpreted within the clinical context and lower colony counts may be significant, especially in a dilute urine

• SPA: > 1,000 cfu/mL
• Cath: > 10,000 cfu/mL
• CCM: > 100,000 cfu/mL

(Hansson 1998 [C], Rushton 1997 [S,E])

Diagnosis

Laboratory Tests

The definitive diagnosis of infection in children requires a positive urine culture. Urine must be obtained under bacteriologically reliable conditions when undertaking a urine specimen culture. A positive urine culture is defined as the presence of more than 100,000 cfu/mL of one pathogen. The urine specimen may be difficult to obtain in a child less than 4 years old and different methods are advised since there is a high risk of contamination.

Collection of the Urine

Suprapubic Bladder Aspiration

Suprapubic bladder aspiration is the most sensitive method, even though urine may be obtained in 23-99% of cases.

Bladder Catheterization

Bladder catheterization is also a most sensitive method, even though there is the risk of introduction of nosocomial pathogens.

Plastic Bag Attached to the Genitalia

Prospective studies showed a high incidence of false-positive results, ranging from 85-99%. It is helpful when the culture is negative and has a positive predictive value of 15%. In order to obtain a urine sample in the best condition in children under 2 years of age (girls and uncircumcised boys without sphincteric control), it is better to use suprapubic bladder aspiration or bladder catheterization. In older children with sphincteric control, MSU collection is possible and reliable.

Quantification of Bacteriuria

The final concentration of bacteria in urine is directly related to the method of collection, diuresis, method of storage and transport of the specimen. The classical definition of significant bacteriuria of more than 10⁵ cfu/mL is still used and depends on the clinical environment.

The presence of pyuria (more than 5 leucocytes per field) and bacteriuria in a fresh urine sample will reinforce the clinical diagnosis of UTI.

In boys, when the urine is obtained by bladder catheterization, the urine culture is considered positive with more than 10⁴ cfu/mL. Even though Hoberman identified a micro-organism in 65% of cases with colony counts between 10,000 and 50,000 cfu/mL, there was a mixed growth pattern suggesting contamination. In these cases, it is better to repeat the culture or to evaluate the presence of other signs, such as pyuria, nitrites or other biochemical markers. The collection of MSU or in a collecting bag of more than 10⁵ cfu/mL is considered positive.

Criteria of UTI in Children

Urine specimen from SPA: Any number of cfu/mL (at least 10 identical colonies)

Urine specimen from bladder catheterization: > 1,000-50,000 cfu/mL

Urine specimen from midstream void: > 10⁴ cfu/mL with symptoms; > 10⁵ cfu/mL without symptoms

Other Biochemical Markers

The presence of other biochemical markers in a urine sample are useful to establish the diagnosis of UTI. The most frequent markers are nitrite and LE usually combined in a dipstick test.

The dipstick test has become useful to exclude rapidly and reliably the presence of a UTI, provided both nitrite and LE tests are negative. If the tests are positive, it is better to confirm the results in combination with the clinical symptoms and other tests.

Bacteriuria without pyuria may be found:

• In bacterial contamination
• In colonization (asymptomatic bacteriuria)
• When collecting a specimen before the onset of an inflammatory reaction

In such cases, it is advisable to repeat the urinalysis after 24 hours to clarify the situation. Even in febrile children with a positive urine culture, the absence of pyuria may cast doubt on the diagnosis of UTI. Instead, asymptomatic bacteriuria with a concomitant septic focus responsible for the febrile syndrome has to be considered.

Bacteriuria without pyuria is found in 0.5% of specimens. This figure corresponds well with the estimated rate of asymptomatic bacteriuria in childhood (IIa).

Pyuria without bacteriuria may be due to:

• Incomplete antimicrobial treatment of UTI
• Urolithiasis and foreign bodies
• Infections caused by Mycobacterium tuberculosis and other fastidious bacteria, e.g., Chlamydia trachomatis.

Thus, either bacteriuria or pyuria may not be considered reliable parameters to diagnose or exclude UTI. Their assessment can be influenced by other factors, such as the degree of hydration, method of specimen collection, mode of centrifugation, volume in which sediment is resuspended and subjective interpretation of results. However, according to Landau et al., pyuria in febrile children is indicative of acute pyelonephritis.

For all of these reasons, in neonates and children under 6 months of age, either pyuria, bacteriuria or the nitrite test, separately, have minimal predictive value for UTI (III). In contrast, the positive predictive value of significant Gram staining with pyuria is 85% (IIb). In older children, pyuria with a positive nitrite test is more reliable for the diagnosis of UTI, with a positive predictive value of 98%.

Combining bacteriuria and pyuria in febrile children, the findings of > 10 WBC/mm³ and > 50,000 cfu/mL in a specimen collected by catheterization are significant for a UTI and discriminate between infection and contamination.

C-reactive Protein

Although non-specific in febrile children with bacteriuria, C-reactive protein seems to be useful in distinguishing between acute pyelonephritis and other causes of bacteriuria. It is considered significant at a concentration above 20 microg/mL.

Urinary N-acetyl-β-glucosaminidase

This is a marker of tubular damage. It is increased in a febrile UTI and may become a reliable diagnostic test for UTIs, although it is also elevated in VUR.

Interleukin-6

The clinical use of urinary concentrations of interleukin-6 in UTIs is still at the research stage.

Admission Criteria

It is recommended that admission be primarily restricted to infants and children:

• Who require IV for fluids
• Who require IV antibiotics due to severe illness or due to lack of response to by mouth (PO) antibiotics

  Note: A high quality, randomized controlled trial demonstrated that oral cefixime is a safe and effective treatment for children age 1 to 24 months with definite UTI (Hoberman 1999 [A]).

• Who are 0 to 30 days of age
• Who are 31 to 60 days of age and identified as high-risk clinically or by laboratory data
• With whom the clinician or family is uncomfortable managing in an outpatient setting

(Local Expert Consensus, [E])

Discharge Criteria

It is recommended that the hospitalized child be discharged as soon as:

• Afebrile for at least 12 hours
• Taking adequate oral fluids
• Pain controlled with oral medications
• Home antibiotics tolerated (PICC line or oral)
• Parent confident in caring for child at home
• Imaging studies are complete or arrangements have been made
• Primary care provider(s) identified, notified, and agree(s) with discharge decision, and arrangements for appropriate follow up have been made

(Local Expert Consensus [E])

Electronic and print distribution; Open access

If the child is severely ill with vomiting and dehydration, hospital admission is required and parenteral antibiotics are given initially (A).

For a safety period of 24-36 hours, parenteral therapy should be administered. When the child becomes afebrile and is able to take fluids, he/she may be given an oral agent to complete the 10-14 days of treatment, which may be continued on an outpatient basis. This provides some advantages, such as less psychological impact on the child and more comfort for the whole family. It is also less expensive, well tolerated and eventually prevents opportunistic infections.

Medications

• It is recommended that a child with presumed UTI be empirically treated with antibiotics after obtaining an appropriate sample for culture. Prompt treatment with antibiotics reduces the severity of renal scarring (Benador 1997 [C], Winberg 1982 [S,E]). See Appendix 7 and Appendix 8 of the original guideline document for summary of recommended doses for parenteral and oral antibiotics, respectively.

  Note: Well-appearing children who are not febrile, and in whom dipstick or urinalysis results are equivocal, can be considered for outpatient observation without starting antibiotic therapy until the subsequent clinical course and culture results are known. As long as uncertainty persists, this course of management assumes:

  • Available reliable follow up as needed
  • Healthcare provider(s) confident that caregiver will use appropriate observational and follow-up skills

  (Local Expert Consensus, [E])

• It is recommended, if the child is diagnosed with a definite UTI, that antibiotic therapy be continued for a minimum of 7 to 14 days (Keren 2002 [M]). Culture and susceptibility results may indicate that a change of antibiotic is necessary. See Appendix 7 and Appendix 8 in the original guideline document for summary of recommended doses for parenteral and oral antibiotics, respectively.
• It is recommended, if the urine culture is negative, that antibiotics be discontinued (Local Expert Consensus [E]).

Follow-Up

• It is recommended, for children who will have imaging, to consider the use of post-treatment antibiotic prophylaxis until radiologic evaluation results are known (Local Expert Consensus, [E]). See Appendix 11 in the original guideline document for a summary of recommended doses of prophylactic antibiotics.

  Note: Uncertainty exists regarding the effectiveness of prophylaxis in improving outcomes (Garin et al., 2006, [A]; Beetz, 2006 [S]). See Appendix 12 in the original guideline document for further information on UTI prophylaxis.

NGC Note: The antibiotics listed below are taken from Appendices 7, 8 and 11 of the original guideline document. Refer to these appendices in the original guideline document for information regarding: dose, frequency and maximum daily dose; taste; relative cost; and comments.

Parenteral Antibiotics for Treatment of UTI (usually inpatient)

• Cefotaxime (Claforan®)
• Ampicillin
• Gentamicin
• Ceftriaxone (Rocephin®)

Antibiotics for Outpatient Treatment of UTI

Recommend minimum of 7 to 14 days treatment.

First-Line Antibiotics Recommended for First UTI

• Cefixime (Suprax®)
• Cephalexin (Biocef®, Keflex®)
• Sulfamethoxazole/Trimethoprim (Bactrim®, Septra®, Generic)

Alternative Antibiotics for Patients with Special Circumstances

• Nitrofurantoin (Macrodantin®, Furadantin®)
• Ciprofloxacin (Cipro®)
• Ceftriaxone (Rocephin®)

Prophylactic Antibiotics

Recommend until radiologic evaluation results are known and duration individualized thereafter.

• Sulfamethoxazole/Trimethoprim (Bactrim®, Septra®, Generic)
• Nitrofurantoin (Macrodantin®, Furadantin®)
• Amoxicillin
• Cephalexin (Biocef®, Keflex®)

Summary and Recommendations

In the treatment of a UTI in children, short courses are not advised and therefore treatment is continued for 5-7 days and longer (A). If the child is severely ill with vomiting and dehydration, hospital admission is required and parenteral antibiotics are given initially (A).

Treatment

Severe UTIs

A severe UTI requires adequate parenteral fluid replacement and appropriate antimicrobial treatment, preferably with cephalosporins (third generation). If a Gram-positive UTI is suspected by Gram stain, it is useful to administer aminoglycosides in combination with ampicillin or amoxycillin/clavulanate (IIa). Antimicrobial treatment has to be initiated on an empirical basis, but should be adjusted according to culture results as soon as possible.

In patients with an allergy to cephalosporins, aztreonam or gentamicin may be used. When aminoglycosides are necessary, serum levels should be monitored for dose adjustment. Chloramphenicol, sulphonamides, tetracyclines, rifampicin, amphotericin B and quinolones should be avoided. The use of ceftriaxone must also be avoided due to its undesired side effect of jaundice.

A wide variety of antimicrobials can be used in older children, with the exception of tetracyclines (because of teeth staining). Fluorinated quinolones may produce cartilage toxicity, but if necessary may be used as second-line therapy in the treatment of serious infections, since musculoskeletal adverse events are of moderate intensity and transient. For a safety period of 24-36 hours, parenteral therapy should be administered. When the child becomes afebrile and is able to take fluids, he/she may be given an oral agent to complete the 10-14 days of treatment, which may be continued on an outpatient basis. This provides some advantages, such as less psychological impact on the child and more comfort for the whole family. It is also less expensive, well tolerated and eventually prevents opportunistic infections. The preferred oral antimicrobials are: TMP, co-trimoxazole (TMP plus sulphamethoxazole), an oral cephalosporin, or amoxycillin/clavulanate. However, the indication for TMP is declining in areas with increasing resistance. In children less than 3 years of age, who have difficulty taking oral medications, parenteral treatment for 7-10 days seems advisable, with similar results to those with oral treatment.

If there are significant abnormalities in the urinary tract (e.g., VUR, obstruction), appropriate urological intervention should be considered. If renal scarring is detected, the patient will need careful follow-up by a paediatrician in anticipation of sequelae such as hypertension, renal function impairment and recurrent UTI.

An overview of the treatment of febrile UTIs in children is given in Figure 3.2 of the original guideline document and the dosing of antimicrobial agents is outlined in Table 3.3 in the original guideline document.

Simple UTIs

A simple UTI is considered to be a low-risk infection in children. Oral empirical treatment with TMP, an oral cephalosporin or amoxycillin/clavulanate is recommended, according to the local resistance pattern. The duration of treatment in uncomplicated UTIs treated orally should be 5-7 days (Ib). A single parenteral dose may be used in cases of doubtful compliance and with a normal urinary tract (IIa). If the response is poor or complications develop, the child must be admitted to hospital for parenteral treatment.

Prophylaxis

If there is an increased risk of pyelonephritis, e.g., VUR, and recurrent UTI, low-dose antibiotic prophylaxis is recommended (IIa). It may also be used after an acute episode of UTI until the diagnostic work-up is completed. The most effective antimicrobial agents are: nitrofurantoin, TMP, cephalexin and cefaclor.

Imaging

Imaging procedures available for children with UTI are described in Appendix 9 of the original guideline document: ultrasound (US), cystogram and renal cortical scan. See also imaging algorithm, page 8 and Appendix 10 (reflux grading system) of the original guideline document.

A primary goal of imaging is to identify structural abnormalities of the urinary tract or bladder that may benefit from surgical or medical intervention. Decisions to perform imaging presume that the findings will sufficiently influence management to justify the burden of testing; for example, the discomfort of catheterization.

Note 1: The diagnostic validity of a cystogram for detection of VUR does not appear to be affected if the procedure is performed during an inpatient stay for treatment of UTI (Mahant 2001 [D]).

Note 2: Routine cystogram and US following a first childhood UTI identifies a small proportion of children with associated treatable conditions. The approximate prevalences of VUR among girls age 0 to 18yrs referred for VCUG after documented UTI (first or subsequent) are: Grade I 7%; Grade II 22%; Grade III 6%; Grade IV 1%; and Grade V <1% (Bisset 1987 [D]). The prevalence of US-identified anatomic abnormalities amenable to surgical correction following first UTI is approximately 1% (Zamir 2004 [C], Bisset 1987 [D]).

• It is recommended, because careful long-term outcomes research has not been performed, that children in the following categories, with a first UTI, have a cystogram and US. See Appendix 9 in the original guideline document.
  • All boys
  • Girls age < 36 months (see Note 1 below)
  • Girls age 3 to 7 years (84 months) with fever > 38.5° C (101.3° F)

  (Gordon 2003 [M], Hoberman 2003 [A], Wennerstrom 2000b [C], Jodal 2000 [S], AAP 1999 [S]).

  Note 1: Although an age break at three years is used, the appropriate age cutoff may depend, in part, on the girl's ability to verbalize dysuria symptoms and/or her status of toilet training (Local Expert Consensus [E]).

  Note 2: A relatively small number of significant anatomic abnormalities will be missed if routine imaging after first UTI is not done (Zamir 2004 [C], Bisset 1987 [D]).

  Note 3: Schedule the US and cystogram for the same date, with the cystogram to follow the US. If an RNC has been ordered, and if there are significant US abnormalities, the Radiology staff physician will ask to substitute a VCUG for the RNC at that appointment (Local Expert Consensus, [E]).

  Note 4: An optional imaging evaluation for children with febrile UTI, especially those over age three years is to first perform US and renal cortical scan (see Appendix 9). This avoids bladder catheterization (part of the cystogram procedure) if the results of the scan are normal. However, if pyelonephritis or cortical scarring is found on the renal cortical scan, a cystogram is indicated (Local Expert Consensus, [E]).

• It is recommended, for children in the following categories, that observation without imaging be considered and that the family share in the decision of whether or not imaging be performed after the first UTI or delayed until after the second UTI, if one occurs:
  • Girls >3 years of age without fever (temperature >38.5 degrees C)
  • All girls >7 years of age

  (Local Expert Consensus, [E])

  Observation without imaging is defined as follow-up with dipstick or routine urinalysis when age-appropriate symptoms of UTI are observed.

  Note 1: For imaging after first or second UTI, one option is to perform a cystogram and US. An alternative, for febrile UTI, is to perform a renal cortical scan and US (see Note 4 in the previous recommendation, and see Appendix 9 in the original guideline document).

  Note 2: Factors influencing choice of imaging option:
  • Clinical symptoms and rate of resolution (see Appendix 5 in the original guideline document)
  • Age (continuously decreasing risk of reflux over age 5 years)
  • Abnormal relevant history (e.g., voiding dysfunction) or physical exam (e.g., sacral dimple)
  • Family input: family understands the imaging procedures, that there is a small chance that an anatomic abnormality exists, and that close follow-up is needed for subsequent UTIs after which imaging may be performed
  • Compliance: confidence that caregiver will use appropriate observational skills and follow-up
  • African-Americans have lower risk of VUR and renal damage (West & Venugopal, 1993 [C]; Chand et al., 2003 [D]; Melhem & Harpen, 1997 [D]; Askari & Belman, 1982 [D])
  • Availability of prenatal US images for review by radiologist (Ismaili et al., 2004 [C]; Chitty et al., 1991 [D])

• It is recommended that a renal cortical scan be considered if identification of acute pyelonephritis or renal scarring will affect management decisions in febrile UTI (Wennerstrom et al., "Ambulatory blood pressure," 2000 [C]; Wennerstrom et al., "Renal function," 2000 [C]; Majd & Rushton, 1992 [S, E]; Rushton et al., 1988 [F]). See Appendix 9 in the original guideline document.

  Note: The long-term significance of scarring identified by a renal cortical scan remains unclear. Factors to be considered are illness severity, grade of VUR, radiation exposure, and avoidance of bladder catheterization.

Summary and Recommendations

Investigations should be undertaken after a maximum of two episodes of a UTI in girls and one in boys (B). The objective is to rule out the unusual occurrence of obstruction, VUR and dysfunctional voiding, e.g., as caused by a neuropathic disorder.

Imaging of the Urinary Tract

A 'gold standard' imaging technique has to be cost-effective, painless, safe, with minimal or nil radiation, and an ability to detect any significant structural anomaly. Current techniques do not fulfill all such requirements.

Ultrasonography

US has become very useful in children because of its safety, speed and high accuracy in identifying the anatomy and size of the renal parenchyma and collecting system. It is subjective and therefore operator-dependent, and gives no information on renal function. However, scars can be identified, although not as well as with Tc-99m DMSA scanning (IIa). This technique has been shown to be very sensitive and excretory urography must be reserved only for when images need to be morphologically clarified (IIa).

Radionuclide Studies

Tc-99m DMSA is a radiopharmaceutical that is bound to the basement membrane of proximal renal tubular cells; half of the dose remains in the renal cortex after 6 hours. This technique is helpful in determining functional renal mass and ensures an accurate diagnosis of cortical scarring by showing areas of hypoactivity indicating lack of function. A UTI interferes with the uptake of this radiotracer by the proximal renal tubular cells, and may show areas of focal defect in the renal parenchyma. A star-shaped defect in the renal parenchyma may indicate an acute episode of pyelonephritis. A focal defect in the renal cortex usually indicates a chronic lesion or a 'renal scar' (IIa).

A focal scarring or a smooth uniform loss of renal substance as demonstrated by Tc-99m DMSA has generally been regarded as being associated with VUR (reflux nephropathy). However, Rushton et al. stated that significant renal scarring may develop, regardless of the existence or absence of VUR. Ransley and Risdon reported that Tc-99m DMSA showed a specificity of 100% and sensitivity of 80% for renal scarring.

The use of Tc-99m DMSA scans can be helpful in the early diagnosis of acute pyelonephritis. About 50-85% of children will show positive findings in the first week. Minimal parenchymal defects, when characterized by a slight area of hypoactivity, can resolve with antimicrobial therapy. However, defects lasting longer than 5 months are considered to be renal scarring (IIa).

Tc-99m DMSA scans are considered more sensitive than excretory urography and ultrasonography in the detection of renal scars. It remains questionable whether radionuclide scans could substitute for echography as a first-line diagnostic approach in children with a UTI.

Cystourethrography

Conventional VCU

VCU is the most widely used radiological exploration for the study of the lower urinary tract and especially of VUR. It is considered mandatory in the evaluation of UTIs in children less than 1 year of age. Its main drawbacks are the risk of infection, the need for retrogrades filling of the bladder and the possible deleterious effect of radiation on children. In recent years, tailored low-dose fluoroscopic VCU has been used for the evaluation of VUR in girls in order to minimize radiological exposure. VCU is mandatory in the assessment of febrile childhood UTI, even in the presence of normal ultrasonography. Up to 23% of these patients may reveal VUR.

Radionuclide Cystography (Indirect)

This investigation is performed by prolonging the period of scanning after the injection of Tc-99m DTPA or MAG-3 as part of a dynamic renography. It represents an attractive alternative to conventional cystography, especially when following patients with reflux, because of its lower dose of radiation. Disadvantages are a poor image resolution and difficulty in detecting lower urinary tract abnormalities.

Cystosonography

Contrast material-enhanced voiding ultrasonography has been introduced for the diagnoses of VUR without irradiation. Further studies are necessary to determine the role of this new imaging modality in UTI.

Additional Imaging

Excretory urography remains a valuable tool in the evaluation of the urinary tract in children, but its use in UTIs is debatable unless preliminary imaging has demonstrated abnormalities requiring further investigation.

Urodynamic Evaluation

When voiding dysfunction is suspected, e.g., incontinence, residual urine, increased bladder wall thickness, urodynamic evaluation with uroflowmetry, (video) cystometry, including pressure flow studies, and electromyography should be considered.

Schedule of Investigation

Screening of infants for asymptomatic bacteriuria is unlikely to prevent pyelonephritic scar formation, as these usually develop very early in infancy. Only a minority of children with a UTI have an underlying urological disorder, but when present such a disorder can cause considerable morbidity. Thus, after a maximum of two UTI episodes in a girl and one episode in a boy, investigations should be undertaken (Figure 3.1 in the original guideline document), but not in the case of asymptomatic bacteriuria. The need for DTPA/MAG-3 scanning is determined by the ultrasound findings, particularly if there is suspicion of an obstructive lesion.

Follow-up

• It is not recommended that routine follow-up urine cultures be conducted during the initial course of inpatient or outpatient therapy.

  Note: In a retrospective study, there were no positive results among follow-up urine cultures in 291 children while hospitalized with UTI. Thirty-two percent of these patients had fever longer than 48 hours (Currie et al., 2003 [D]).

• It is recommended that follow-up assessment for expected clinical response occur after 48 to 72 hours of antimicrobial therapy. Culture and susceptibility results may indicate that a change of antibiotic is necessary. If expected clinical improvement is lacking, consider further evaluation which may include laboratory studies, imaging, and/or consultation with specialists (Local Expert Consensus, [E]).
• It is recommended that families and clinicians maintain a high index of suspicion for recurrent UTI, and to obtain a dipstick, urinalysis, and/or culture for age-appropriate symptoms of UTI, including unexplained fever (Wennerstrom et al., "Ambulatory blood pressure," [C]; Local Expert Consensus, [E]). See Table above titled "Clinical Signs and Symptoms of UTI". Screening urine cultures are not necessary (Wettergren et al., 1990, [C]).

  Note: Low rates of scarring, hypertension, and loss of renal function have been attributed to aggressive assessment of febrile illnesses and treatment of recurrent UTI (Wennerstrom et al., "Ambulatory blood pressure," [C]; Wennerstrom et al., "Renal function," 2000 [C]; Wennerstrom et al., "Primary and acquired," 2000 [C]).

• It is recommended, for children who will have imaging, to consider the use of post-treatment antibiotic prophylaxis until radiologic evaluation results are known (Local Expert Consensus, [E]). See appendix 11 in the original guideline document for a summary of recommended doses of prophylactic antibiotics.

  Note: Uncertainty exists regarding the effectiveness of prophylaxis in improving outcomes (Garin et al., 2006, [A]; Beetz, 2006 [S]). See Appendix 12 in the original guideline document for further information on UTI prophylaxis.

Consults and Referrals

• It is recommended that consultation with a specialist in childhood renal disorders be considered:
  • When uncertain about the management of a child with documented or suspected vesicoureteral reflux, renal scarring, or structural abnormalities of the urinary tract
  • If a renal or bladder stone is identified

  (Local Expert Consensus, [E]).

• It is recommended that a consultation with Infectious Diseases be considered when there are questions about antibiotic selection or unusual organisms (Local Expert Consensus, [E]).

Severe UTIs

If there are significant abnormalities in the urinary tract (e.g., VUR, obstruction), appropriate urological intervention should be considered. If renal scarring is detected, the patient will need careful follow-up by a paediatrician in anticipation of sequelae such as hypertension, renal function impairment and recurrent UTI.

Education

Health Topics on CCHMC's website:

• Urine Culture: Adult Assisting a Female Child
• Urine Culture: Adult Assisting a Male Child
• Vesicoureteral Reflux/VUR

Imaging Procedures:

• Kidney Ultrasound (US)
• Renal Cortical Scan/DMSA

A parent information brochure, Urinary Tract Infections in Young Children is available for bulk purchase from the AAP.

No recommendations offered.

• Improved use of appropriate diagnostic criteria
• Improved use of appropriate antibiotic therapy
• Improved use of appropriate imaging studies
• Avoidance of long-term medical problems
• Improved parental involvement in decision-making around the management of UTIs
• Identification of the infants and children at most risk for long-term renal damage

• Cure of UTIs
• Reduction in UTI recurrences
• Avoidance of long-term medical problems

• Burden of imaging (e.g., discomfort of catheterization, radiation exposure) versus missed identification of treatable anatomic abnormalities
• Use of amoxicillin for treatment of the acute UTI may be limited due to increasing resistance.
• Ceftriaxone and sulfamethoxazole/trimethoprim should be used with caution in jaundiced infants.
• Limitations of radiologic imaging: ultrasound has limited accuracy in evaluation of renal scarring or pyelonephritis; radionuclide cystogram provides little anatomic detail; x-ray voiding cystourethrogram involves ionizing radiation; renal cortical scan requires intravenous injection of radioisotope, with imaging about 2 hours later for about 45 minutes)

• Exposure to radiation from diagnostic imaging
• Side effects of antibiotics

Cincinnati Children's Hospital and Medical Center Grading Scale

M: Meta-analysis
A: Randomized controlled trial: large sample
B: Randomized controlled trial: small sample
C: Prospective trial or large case series
D: Retrospective analysis
O: Other evidence
S: Review article
E: Expert opinion or consensus
F: Basic laboratory research
L: Legal requirement
Q: Decision analysis
X: No evidence

References Supporting the Recommendations

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Bachur RG, Harper MB. Predictive model for serious bacterial infections among infants younger than 3 months of age. Pediatrics 2001 Aug;108(2):311-6. PubMed

Beetz R. May we go on with antibacterial prophylaxis for urinary tract infections? Pediatr Nephrol 2006 Jan;21(1):5-13. [76 references] PubMed

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Levels of Evidence

Ia Evidence obtained from meta-analysis of randomized trials

Ib Evidence obtained from at least one randomized trial

IIa Evidence obtained from at least one well-designed controlled study without randomization

IIb Evidence obtained from at least one other type of well-designed quasi-experimental study

III Evidence obtained from well-designed non-experimental studies, such as comparative studies, correlation studies and case reports

IV Evidence obtained from expert committee reports or opinions or clinical experience of respected authorities

Grades of Recommendation

A Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomized trial

B Based on well-conducted clinical studies, but without randomized clinical studies

C Made despite the absence of directly applicable clinical studies of good quality