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Urinary Tract Infection in Children
BRIAN S. ALPER, M.D., M.S.P.H., and SARAH H. CURRY, M.D.
University of Missouri–Columbia, Columbia, Missouri

Up to 7 percent of girls and 2 percent of boys will have a symptomatic, culture-confirmed
urinary tract infection by six years of age. Urinary tract infection may be suspected because of
urinary symptoms in older children or because of fever, nonspecific symptoms, or failure to
thrive in infants. Urine dipstick analysis is useful for ruling out urinary tract infections in cases
with low clinical suspicion. However, urine culture is necessary for diagnosis of urinary tract
infections in children if there is high clinical suspicion, cloudy urine, or if urine dipstick testing
shows positive leukocyte esterase or nitrite activity. Despite current recommendations, routine
imaging studies (e.g., renal ultrasonography, voiding cystourethrography, renal scans) do not
appear to improve clinical outcomes in uncomplicated urinary tract infections. Oral antibiotics
are as effective as parenteral therapy in randomized trials. The optimal duration of antibiotic
therapy has not been established, but one-day therapies have been shown to be inferior to longer
treatment courses. (Am Fam Physician 2005;72:2483-8. Copyright © 2005 American Academy
of Family Physicians.)




                             U
 EB C M E                                ntil recently, the management of       and infrequent voiding in two studies4,5 but
                                         urinary tract infection (UTI) in       not in a cohort of febrile children younger
This clinical content con-
forms to AAFP criteria for               children has been controversial        than two years.6 Bathing and back-to-front
evidence-based continuing                and based mainly on opinion,           wiping have not been demonstrated to be
medical education (EB        but new evidence regarding imaging stud-           risk factors.
CME). EB CME is clinical
                             ies and treatment prompted this review.
content presented with
practice recommendations     Although symptomatic UTI and asymptom-             Evaluation
supported by evidence        atic bacteriuria (i.e., positive urine cultures    Older children with UTI may have dysuria,
that has been reviewed       without symptoms or signs of illness) are          frequency, urgency, hesitancy, small-volume
systematically by an
AAFP-approved source.
                             discussed in the literature, this review focuses   voids, or lower abdominal pain. Infants with
                             on symptomatic UTI.                                UTI more commonly present with non-
                                                                                specific symptoms such as fever, irritabil-
                             Epidemiology                                       ity, jaundice, vomiting, or failure to thrive.
                             Up to 7 percent of girls and 2 percent of boys     Unusual odor of the urine is not helpful in
                             will have a symptomatic, culture-confirmed         predicting UTI.7
                             UTI by six years of age.1 The prevalence of           Other conditions may mimic UTI symp-
                             UTI in febrile infants is greater with younger     toms. Acute urethritis or vulvovaginitis may
                             age, with a rate of nearly 7 percent among         be caused by various types of irritants,
                             febrile newborns.2                                 including chemical (e.g., bubble baths,
                               Most UTIs in children result from ascend-        soaps), physical (e.g., self-exploration), and
                             ing infections, although hematogenous              biologic (e.g., pinworms). Self-infusion of
                             spread may be more common in the first             water into the urethra was reported in 10
                             12 weeks of life. Most UTIs in children are        of 31 boys five to 15 years of age presenting
                             monomicrobic, often caused by Escherichia          with a first UTI.8
                             coli (60 to 80 percent of cases), Proteus
                                                                                urinE culturE
                             (more common in boys and in children with
                             renal stones), Klebsiella, Enterococcus, and       Urine culture is required for diagnosis of
                             coagulase-negative staphylococci. 3                UTI. The diagnostic threshold depends on the
                               Evidence on risk factors for UTI in chil-        method of urine collection. Compilation of
                             dren is limited. UTIs were associated with         studies comparing counts of colony-forming
                             constipation, encopresis, bladder instability,     units from various collection methods with

December 15, 2005 ◆ Volume 72, Number 12	                 www.aafp.org/afp	                     American Family Physician  2483
uti in children




    sOrt: KEY rEcOMMEndatiOns FOr practicE

                                                                                                                     Evidence
   Clinical recommendation                                                                                           rating        References

   Urine culture should be obtained for diagnosis of UTI in children if there is high clinical suspicion,            C             13-16
     cloudy urine, or positive urine dipstick.
   Routine imaging studies (e.g., ultrasonography, VCUG, renal scans) do not appear to improve                       B             24, 26, 27
     outcomes in children with a first uncomplicated UTI, but the evidence is weak.
   Oral antibiotics should be used (when tolerated) instead of parenteral antibiotics to manage UTI                  A             35, 36
     in children.
   One-day courses of antibiotics should not be used to manage UTI in children.                                      A             37
   Consider that short courses of antibiotics (two to five days) may be as effective as longer courses               B             37-39
     (seven to 14 days).
   Prophylactic antibiotics may be used to reduce the risk of recurrent UTI.                                         B             42, 43

   UTI = urinary tract infection; VCUG = voiding cystourethrography.
   A = consistent, good quality patient-oriented evidence; B = inconsistent or limited quality patient-oriented evidence; C = consensus, disease-
   oriented evidence, usual practice, expert opinion, or case series. For more information about the SORT evidence rating system, see page 2416 or
   http://www.aafp.org/afpsort.xml.



the probability of UTI has established the recommenda-                      use of pads or bags, but this method is reasonably accu-
tions listed in Table 1.9                                                   rate and rates of contamination are low.11,12
   For urine collection from infants and young children,
                                                                            rapid urinE tEsting
suprapubic aspiration or transurethral catheterization
generally is recommended. Urethral catheterization                          Children with a high likelihood of UTI (e.g., older chil-
is more likely than aspiration to obtain a sufficient                       dren with classic urinary symptoms) should have a urine
sample of urine.10 Collection from bags or pads leads to                    culture; rapid urine testing will not change the treatment
high contamination rates.11 Clean-catch urine collection                    of these patients. In children with a low likelihood of
from infants requires more patience and effort than the                     UTI (e.g., those with vague urinary complaints and an
                                                                            alternative explanation for fever), urine inspection and
                                                                            dipstick testing may reduce the need for urine culture.
  table 1
                                                                            Urine culture is indicated if the child’s urine is cloudy
  diagnostic thresholds for uti in children 
                                                                            or if the dipstick test shows positive leukocyte esterase
                                                                            or nitrite activity.13-16 Urine culture also is recommended
  Method of
  urine collection        Diagnostic threshold                              for children with recurrent symptoms.
                                                                               Urine dipstick analysis can rule out UTI if the result is
  Clean-catch             100,000 CFU per mL                                negative (in nondilute urine), but a positive result on dip-
   voiding in girls       Repeat testing if 10,000 to 100,000
                                                                            stick testing is insufficient to diagnose UTI because false-
                           CFU per mL
                                                                            positive results are common. In a cohort study13 with
  Clean-catch             10,000 CFU per mL
   voiding in boys                                                          18 percent prevalence of UTI, a negative result on urine
  Catheter                10,000 CFU per mL                                 dipstick analysis (i.e., negative for leukocyte esterase and
                          Repeat testing if 1,000 to 10,000                 nitrites) had a negative predictive value of 96 percent.
                           CFU per mL                                       Urine dipstick analysis appears to be more accurate than
  Suprapubic              Any number of colonies for gram-                  microscopic analysis for the detection of pyuria in chil-
   aspiration              negative bacilli, more than a few                dren,13,14 although this has been debated.17 Urine dipstick
                           thousand CFU per mL for gram-
                                                                            analysis may produce false-negative results with dilute
                           positive cocci
                                                                            urine (i.e., specific gravity less than 1.005). Clear urine
  UTI = urinary tract infection; CFU = colony-forming units.                (defined as the ability to read text through the urine in a
  Adapted with permission from Hellerstein S. Recurrent urinary tract       test tube as easily as through water) had 96 to 100 percent
  infections in children. Pediatr Infect Dis 1982;1:275.                    negative predictive values in cohort studies,13,15,16 but
                                                                            these values may be unreliable in dilute urine.

2484  American Family Physician                                   www.aafp.org/afp	                Volume 72, Number 12 ◆ December 15, 2005
uti in children




   Some authors recommend urine culture testing for            management (i.e., no obstructive lesions were found).
infants with suspected UTI because of lower sensitivi-         Initial renal scans suggested acute pyelonephritis in
ties for urine dipstick analysis in infants.18,19 However,     61 percent of patients, but febrile UTI in infants is man-
investigators in several large cohort studies2,20 of infants   aged with the presumption of pyelonephritis. VCUG and
younger than two years with undiagnosed fevers or UTI          repeat renal scans showed vesicoureteral reflux (VUR)
symptoms have found negative predictive values greater         and renal scarring in 39 and 9.5 percent of infants,
than 98 percent despite sensitivities of 79 percent. Urine     respectively. However, the manner in which VUR or renal
dipstick testing achieved these high negative predictive       scarring should alter the course of management is contro-
values because of the low likelihood of positive urine         versial. In some reviews,28,29 authors have suggested that
cultures (2.8 to 8 percent) in these studies.2,20              VUR predisposes children to recurrent pyelonephritis
                                                               and renal scarring. Although some children with renal
additiOnal tEsting                                             scarring develop hypertension and renal insufficiency
Blood cultures are unnecessary in most children with           in adulthood, this association appears limited to those
UTI, but they are more likely to be positive in chil-          with extensive renal scarring or hypertension in child-
dren younger than two months and in children whose             hood.28 Recommendations have been made to identify
urine cultures grow Staphylococcus aureus or group B           VUR early to stop this cascade of events, despite a lack
streptococcus.21,22                                            of studies showing
   Previously, imaging studies were recommended for            that interventions          surgical and medical man-
any child with a UTI. The 1999 clinical practice guide-        along this pathway          agement for vesicoureteral 
line23 from the American Academy of Pediatrics (AAP)           prevent renal scar-
                                                                                           reflux do not appear to 
recommends imaging for children two months to two              ring, hypertension,
                                                                                           differ in urinary tract infec-
years of age, noting that the strength of evidence for the     and renal insuffi-
                                                                                           tion recurrence rates, renal 
recommendation is fair. Recent evidence has suggested          ciency. Severe VUR
                                                                                           function, renal scarring, 
that imaging work-ups for children with a first uncom-         has been associ-
                                                                                           hypertension, or end-stage 
plicated UTI may not improve patient care. In one pro-         ated with recurrent
spective study,24 renal ultrasonography did not change         UTI and recur-
                                                                    30                     renal disease.
the management of UTI in any of 255 children younger           rent pyelonephri-
than five years who were admitted with a first uncom-          tis,31 but the association of VUR with renal scarring has
plicated febrile UTI. An earlier systematic review25 of        been inconsistent.32,33 Renal scarring is associated with
63 descriptive studies found no evidence of the impact of      recurrent UTI32 and recurrent pyelonephritis,34 but a
routine imaging on clinical outcomes in children with a        causal relationship has not been established.25
first UTI.                                                        Although imaging traditionally has been recom-
   In a randomized trial,26 150 children two to 10 years       mended in children with recurrent UTI, no randomized
of age with a first UTI were assigned to routine imaging       trials are available to support or refute these recommen-
(i.e., ultrasonography and voiding cystourethrography          dations. Bladder ultrasonography to determine postvoid
[VCUG]) or to selective imaging (only if recurrent UTI         residual volume may identify urinary obstruction, and
or persistent problems were present). Approximately            children with renal scarring may benefit from follow-up
one in five children (21 percent) in the selective imag-       for early detection of hypertension or renal insufficiency,
ing group had imaging performed. Routine imaging               but data supporting these approaches are sparse.
increased the use of prophylactic antibiotics (28 versus
5 percent) but did not reduce the rate of recurrent UTIs       treatment
(26 versus 21 percent) or renal scarring at two years          Empiric antibiotic therapy (Table 223) is reasonable while
(9 versus 9 percent). These results suggest that imaging       awaiting culture results if there is a high clinical suspicion
is not useful in determining which children might ben-         of UTI.23 Subsequently changing antibiotics based on
efit from prophylactic antibiotics.                            reported sensitivities may be unnecessary if clinical reso-
   Extensive imaging work-up (i.e., ultrasonography and        lution occurs. According to the AAP, the child should be
renal scan within 72 hours, VCUG at one month, and             reevaluated with a repeat urine culture and renal/bladder
repeat renal scan at six months) was evaluated in a pro-       ultrasonography if clinical improvement does not occur
spective study27 of 309 children one to 24 months of age       within two days.23
with a first febrile UTI. Results of ultrasonography were        The authors of randomized trials35,36 comparing oral
normal in 88 percent, and abnormalities did not change         and parenteral regimens in children with fever and

December 15, 2005 ◆ Volume 72, Number 12	             www.aafp.org/afp	                     American Family Physician  2485
uti in children




positive urine cultures did not find differences in cure
rates or speed of improvement. Parenteral antibiotics may                table 2
be necessary if vomiting precludes oral administration.                  Empiric Oral antibiotic therapy  
   The optimal duration of antibiotic therapy has not                    for uti in children
been established. One-day courses of antibiotics are less
effective than longer courses.37 Systematic reviews37-39 of              Antibiotic                   Daily dosage
randomized trials comparing shorter and longer courses                   Amoxicillin                  20 to 40 mg per kg in three doses*
of antibiotics have had varying results, based in part on                Cefixime (Suprax)            8 mg per kg in two doses
the inclusion of one-day courses in the analysis. Short                  Cefpodoxime                  10 mg per kg in two doses
courses (three to five days) of antibiotics may be as effec-               (Vantin)
tive as longer courses (seven to 14 days), but this has not              Cefprozil (Cefzil)           30 mg per kg in two doses
been clearly proved.37-39                                                Cephalexin (Keflex)          50 to 100 mg per kg in four doses
   No evidence was found to support a recommendation                     Loracarbef (Lorabid)         15 to 30 mg per kg in two doses
for routine posttreatment urine cultures in children                     Sulfisoxazole                120 to 150 mg per kg in four doses
with UTIs. In one study40 of 364 children hospitalized                     (Gantrisin)
with UTI, 291 (80 percent) had follow-up urine cultures,                 Trimethoprim/                6 to 12 mg per kg/30 to 60 mg per
none of which was positive.                                                sulfamethoxazole             kg in two doses
                                                                           (Bactrim, Septra)
prevention
                                                                         UTI = urinary tract infection.
In a one-year longitudinal study,41 recurrent symptom-                   *—Amoxicillin is the first choice for infants younger than two
atic UTI occurred in 12 percent of children younger than                 months.
five years presenting to an emergency department with a                  Adapted with permission from Committee on Quality Improvement,
first UTI. Children younger than six months had a higher                 Subcommittee on Urinary Tract Infection. Practice parameter: the diag-
                                                                         nosis, treatment, and evaluation of the initial urinary tract infection
risk of recurrence (18.6 percent).
                                                                         in febrile infants and young children [published corrections appear in
   Prophylactic antibiotics may reduce the risk of recur-                Pediatrics 2000;105:141, 1999;103:1052, and 1999;104:118]. Pediat-
rent UTI. Two systematic reviews42,43 found weak evidence                rics 1999;103:848.
of benefit with poor quality trials. Table 323 describes
potential prophylactic regimens in children younger
than two years. Only one comparison trial of antibiotic                because of side effects (number needed to treat to
selection was found. In this six-month trial,44 nitrofuran-            harm = 5.3), which were mainly gastrointestinal.
toin (Furadantin) was more effective than trimethoprim                    Because VUR has been considered a predisposing fac-
(Primsol) in preventing UTIs (number needed to treat                   tor to UTI and its complications, treatments for children
[NNT] = 5.4) but was more likely to be discontinued                    with VUR have been promoted. Medical management
                                                                       often has used prophylactic antibiotics, but the system-
                                                                       atic reviews43 suggesting that prophylactic antibiotics
the authors                                                            prevent recurrent UTI did not include studies of children
BRIAN S. ALPER, M.D., M.S.P.H., is a research assistant professor      with VUR. Nonetheless, the AAP recommends prophy-
in the Department of Family and Community Medicine at the              laxis until imaging studies are completed and until
University of Missouri–Columbia School of Medicine. Dr. Alper also     additional treatment based on the imaging findings is
is editor-in-chief of DynaMed. Dr. Alper received his medical degree
from the Hahnemann University School of Medicine, Philadelphia.
                                                                       instituted.23 Two systematic reviews45,46 of randomized
He completed a family medicine residency at Pennsylvania State         trials comparing surgical and medical management of
University/Good Samaritan Hospital in Lebanon, and a family            VUR found no significant differences in UTI recurrence
medicine faculty development fellowship at the University of           rates, renal function, renal scarring, hypertension, or
Missouri–Columbia.                                                     end-stage renal disease. In two randomized trials47,48
SARAH H. CURRY, M.D., is a resident in the University of Missouri–     involving more than 400 children younger than 11 years
Columbia Family and Community Medicine residency program.              who had grade III or IV VUR and documented UTI,
Dr. Curry received her medical degree from the University of           surgery reduced the rate of acute pyelonephritis (21 to
Missouri–Columbia School of Medicine.                                  22 percent incidence with surgery versus 8 to 10 percent
Address correspondence to Brian S. Alper, M.D., M.S.P.H.,
                                                                       with antibiotic prophylaxis alone; NNT = 7 to 9), but
DynaMed LLC, 10 Estes St., Ipswich, MA 01938 (e-mail: editor@          overall rates of UTI did not differ. A new treatment
dynamicmedical.com). Reprints are not available from the authors.      for children with VUR, dextranomer/hyaluronic acid

2486  American Family Physician                              www.aafp.org/afp	                Volume 72, Number 12 ◆ December 15, 2005
uti in children




                                                                                  Data sources: Online sources including PubMed, The
  table 3                                                                       Cochrane Library, Clinical Evidence, DynaMed, and
  antibiotic choices for uti prophylaxis                                        the National Guideline Clearinghouse were searched in
  in children                                                                   April 2003 using “urinary tract infection” and age limi-
                                                                                tations (younger than 18 years) where applicable. Refer-
  Antibiotic                          Dosage                                    ence lists of retrieved articles and reviews also were used.
  Methenamine mandelate               75 mg per kg per day                      The highest level of evidence found for each specific
    (Mandelamine)                       in two doses                            topic was included. This review is based on a more thor-
  Nalidixic acid (NegGram)            30 mg per kg per day                      ough version of this topic that is available in DynaMed
                                        in two doses                            (http://www.DynamicMedical.com) and is updated as
  Nitrofurantoin (Furadantin)         1 to 2 mg per kg once per day             additional relevant information is identified.53
  Sulfisoxazole (Gantrisin)           10 to 20 mg per kg
                                        per day in two doses                    The authors would like to thank J. Lynn Teague, M.D., F.A.A.P., Associate
  Trimethoprim/                       2 mg per kg/10 mg                         Professor of Clinical Surgery, Urology and Child Health, University of
    sulfamethoxazole                    per kg nightly                          Missouri–Columbia, for clinical and editorial feedback and for providing
    (Bactrim, Septra)                                                           expert recommendations.
                                        or
                                      5 mg per kg/25 mg                         Author disclosure: Dr. Alper is editor-in-chief of DynaMed.
                                        per kg twice per week

  UTI = urinary tract infection.                                                rEFErEncEs
  Adapted with permission from Committee on Quality Improvement,                 1. Marild S, Jodal U. Incidence rate of first-time symptomatic urinary tract
  Subcommittee on Urinary Tract Infection. Practice parameter: the diag-            infection in children under 6 years of age. Acta Paediatr 1998;87:
  nosis, treatment, and evaluation of the initial urinary tract infection in        549-52.
  febrile infants and young children [published corrections appear in Pedi-      2. Bachur R, Harper MB. Reliability of the urinalysis for predicting urinary
  atrics 2000;105:141, 1999;103:1052, and 1999;104:118]. Pediatrics                 tract infections in young febrile children. Arch Pediatr Adolesc Med
  1999;103:849.                                                                     2001;155:60-5.
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                                                                                    and risk factors. J R Soc Health 2000;120:220-6.
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scopically near the distal ureteral orifice. Deflux was                             Pediatrics 1997;100:228-32.
more effective than antibiotic prophylaxis in resolving                          5. Koff SA, Wagner TT, Jayanthi VR. The relationship among dysfunctional
childhood VUR in one randomized trial49 of 61 children                              elimination syndromes, primary vesicoureteral reflux and urinary tract
                                                                                    infections in children. J Urol 1998;160:1019-22.
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                                                                                 6. Shaikh N, Hoberman A, Wise B, Kurs-Lasky M, Kearney D, Naylor S,
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   Cranberry juice and related products have not been                               2003;112:1134-7.
shown to prevent or reduce UTI in children; in a sys-                            7. Struthers S, Scanlon J, Parker K, Goddard J, Hallett R. Parental report-
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tematic review50 of seven trials, the evidence base was                             250-2.
too limited to support such conclusions.                                        8. Labbe J. Self-induced urinary tract infection in school-age boys. Pediat-
   Circumcision prevented recurrent symptomatic UTI                                rics 1990;86:703-6.
in one randomized trial.51 Seventy uncircumcised boys                            9. Hellerstein S. Recurrent urinary tract infections in children. Pediatr
                                                                                    Infect Dis 1982;1:271-81.
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because 195 circumcisions would be needed to prevent                            14. Gorelick MH, Shaw KN. Screening tests for urinary tract infection in
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30. Nuutinen M, Uhari M. Recurrence and follow-up after urinary tract                 grades III and IV primary vesicoureteral reflux (United States). The Inter-
    infection under the age of 1 year. Pediatr Nephrol 2001;16:69-72.                 national Reflux Study in Children. J Urol 1992;148:1667-73.
31. Hellerstein S, Nickell E. Prophylactic antibiotics in children at risk for    49. Capozza N, Caione P. Dextranomer/hyaluronic acid copolymer implan-
    urinary tract infection. Pediatr Nephrol 2002;17:506-10.                          tation for vesico-ureteral reflux: a randomized comparison with antibi-
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    young febrile children. Pediatrics 1999;104:79-86.




2488  American Family Physician                                         www.aafp.org/afp	                 Volume 72, Number 12 ◆ December 15, 2005

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Urinary Tract Infection In Children

  • 1. Urinary Tract Infection in Children BRIAN S. ALPER, M.D., M.S.P.H., and SARAH H. CURRY, M.D. University of Missouri–Columbia, Columbia, Missouri Up to 7 percent of girls and 2 percent of boys will have a symptomatic, culture-confirmed urinary tract infection by six years of age. Urinary tract infection may be suspected because of urinary symptoms in older children or because of fever, nonspecific symptoms, or failure to thrive in infants. Urine dipstick analysis is useful for ruling out urinary tract infections in cases with low clinical suspicion. However, urine culture is necessary for diagnosis of urinary tract infections in children if there is high clinical suspicion, cloudy urine, or if urine dipstick testing shows positive leukocyte esterase or nitrite activity. Despite current recommendations, routine imaging studies (e.g., renal ultrasonography, voiding cystourethrography, renal scans) do not appear to improve clinical outcomes in uncomplicated urinary tract infections. Oral antibiotics are as effective as parenteral therapy in randomized trials. The optimal duration of antibiotic therapy has not been established, but one-day therapies have been shown to be inferior to longer treatment courses. (Am Fam Physician 2005;72:2483-8. Copyright © 2005 American Academy of Family Physicians.) U EB C M E ntil recently, the management of and infrequent voiding in two studies4,5 but urinary tract infection (UTI) in not in a cohort of febrile children younger This clinical content con- forms to AAFP criteria for children has been controversial than two years.6 Bathing and back-to-front evidence-based continuing and based mainly on opinion, wiping have not been demonstrated to be medical education (EB but new evidence regarding imaging stud- risk factors. CME). EB CME is clinical ies and treatment prompted this review. content presented with practice recommendations Although symptomatic UTI and asymptom- Evaluation supported by evidence atic bacteriuria (i.e., positive urine cultures Older children with UTI may have dysuria, that has been reviewed without symptoms or signs of illness) are frequency, urgency, hesitancy, small-volume systematically by an AAFP-approved source. discussed in the literature, this review focuses voids, or lower abdominal pain. Infants with on symptomatic UTI. UTI more commonly present with non- specific symptoms such as fever, irritabil- Epidemiology ity, jaundice, vomiting, or failure to thrive. Up to 7 percent of girls and 2 percent of boys Unusual odor of the urine is not helpful in will have a symptomatic, culture-confirmed predicting UTI.7 UTI by six years of age.1 The prevalence of Other conditions may mimic UTI symp- UTI in febrile infants is greater with younger toms. Acute urethritis or vulvovaginitis may age, with a rate of nearly 7 percent among be caused by various types of irritants, febrile newborns.2 including chemical (e.g., bubble baths, Most UTIs in children result from ascend- soaps), physical (e.g., self-exploration), and ing infections, although hematogenous biologic (e.g., pinworms). Self-infusion of spread may be more common in the first water into the urethra was reported in 10 12 weeks of life. Most UTIs in children are of 31 boys five to 15 years of age presenting monomicrobic, often caused by Escherichia with a first UTI.8 coli (60 to 80 percent of cases), Proteus urinE culturE (more common in boys and in children with renal stones), Klebsiella, Enterococcus, and Urine culture is required for diagnosis of coagulase-negative staphylococci. 3 UTI. The diagnostic threshold depends on the Evidence on risk factors for UTI in chil- method of urine collection. Compilation of dren is limited. UTIs were associated with studies comparing counts of colony-forming constipation, encopresis, bladder instability, units from various collection methods with December 15, 2005 ◆ Volume 72, Number 12 www.aafp.org/afp American Family Physician  2483
  • 2. uti in children sOrt: KEY rEcOMMEndatiOns FOr practicE Evidence Clinical recommendation rating References Urine culture should be obtained for diagnosis of UTI in children if there is high clinical suspicion, C 13-16 cloudy urine, or positive urine dipstick. Routine imaging studies (e.g., ultrasonography, VCUG, renal scans) do not appear to improve B 24, 26, 27 outcomes in children with a first uncomplicated UTI, but the evidence is weak. Oral antibiotics should be used (when tolerated) instead of parenteral antibiotics to manage UTI A 35, 36 in children. One-day courses of antibiotics should not be used to manage UTI in children. A 37 Consider that short courses of antibiotics (two to five days) may be as effective as longer courses B 37-39 (seven to 14 days). Prophylactic antibiotics may be used to reduce the risk of recurrent UTI. B 42, 43 UTI = urinary tract infection; VCUG = voiding cystourethrography. A = consistent, good quality patient-oriented evidence; B = inconsistent or limited quality patient-oriented evidence; C = consensus, disease- oriented evidence, usual practice, expert opinion, or case series. For more information about the SORT evidence rating system, see page 2416 or http://www.aafp.org/afpsort.xml. the probability of UTI has established the recommenda- use of pads or bags, but this method is reasonably accu- tions listed in Table 1.9 rate and rates of contamination are low.11,12 For urine collection from infants and young children, rapid urinE tEsting suprapubic aspiration or transurethral catheterization generally is recommended. Urethral catheterization Children with a high likelihood of UTI (e.g., older chil- is more likely than aspiration to obtain a sufficient dren with classic urinary symptoms) should have a urine sample of urine.10 Collection from bags or pads leads to culture; rapid urine testing will not change the treatment high contamination rates.11 Clean-catch urine collection of these patients. In children with a low likelihood of from infants requires more patience and effort than the UTI (e.g., those with vague urinary complaints and an alternative explanation for fever), urine inspection and dipstick testing may reduce the need for urine culture. table 1 Urine culture is indicated if the child’s urine is cloudy diagnostic thresholds for uti in children  or if the dipstick test shows positive leukocyte esterase or nitrite activity.13-16 Urine culture also is recommended Method of urine collection Diagnostic threshold for children with recurrent symptoms. Urine dipstick analysis can rule out UTI if the result is Clean-catch 100,000 CFU per mL negative (in nondilute urine), but a positive result on dip- voiding in girls Repeat testing if 10,000 to 100,000 stick testing is insufficient to diagnose UTI because false- CFU per mL positive results are common. In a cohort study13 with Clean-catch 10,000 CFU per mL voiding in boys 18 percent prevalence of UTI, a negative result on urine Catheter 10,000 CFU per mL dipstick analysis (i.e., negative for leukocyte esterase and Repeat testing if 1,000 to 10,000 nitrites) had a negative predictive value of 96 percent. CFU per mL Urine dipstick analysis appears to be more accurate than Suprapubic Any number of colonies for gram- microscopic analysis for the detection of pyuria in chil- aspiration negative bacilli, more than a few dren,13,14 although this has been debated.17 Urine dipstick thousand CFU per mL for gram- analysis may produce false-negative results with dilute positive cocci urine (i.e., specific gravity less than 1.005). Clear urine UTI = urinary tract infection; CFU = colony-forming units. (defined as the ability to read text through the urine in a Adapted with permission from Hellerstein S. Recurrent urinary tract test tube as easily as through water) had 96 to 100 percent infections in children. Pediatr Infect Dis 1982;1:275. negative predictive values in cohort studies,13,15,16 but these values may be unreliable in dilute urine. 2484  American Family Physician www.aafp.org/afp Volume 72, Number 12 ◆ December 15, 2005
  • 3. uti in children Some authors recommend urine culture testing for management (i.e., no obstructive lesions were found). infants with suspected UTI because of lower sensitivi- Initial renal scans suggested acute pyelonephritis in ties for urine dipstick analysis in infants.18,19 However, 61 percent of patients, but febrile UTI in infants is man- investigators in several large cohort studies2,20 of infants aged with the presumption of pyelonephritis. VCUG and younger than two years with undiagnosed fevers or UTI repeat renal scans showed vesicoureteral reflux (VUR) symptoms have found negative predictive values greater and renal scarring in 39 and 9.5 percent of infants, than 98 percent despite sensitivities of 79 percent. Urine respectively. However, the manner in which VUR or renal dipstick testing achieved these high negative predictive scarring should alter the course of management is contro- values because of the low likelihood of positive urine versial. In some reviews,28,29 authors have suggested that cultures (2.8 to 8 percent) in these studies.2,20 VUR predisposes children to recurrent pyelonephritis and renal scarring. Although some children with renal additiOnal tEsting scarring develop hypertension and renal insufficiency Blood cultures are unnecessary in most children with in adulthood, this association appears limited to those UTI, but they are more likely to be positive in chil- with extensive renal scarring or hypertension in child- dren younger than two months and in children whose hood.28 Recommendations have been made to identify urine cultures grow Staphylococcus aureus or group B VUR early to stop this cascade of events, despite a lack streptococcus.21,22 of studies showing Previously, imaging studies were recommended for that interventions surgical and medical man- any child with a UTI. The 1999 clinical practice guide- along this pathway agement for vesicoureteral  line23 from the American Academy of Pediatrics (AAP) prevent renal scar- reflux do not appear to  recommends imaging for children two months to two ring, hypertension, differ in urinary tract infec- years of age, noting that the strength of evidence for the and renal insuffi- tion recurrence rates, renal  recommendation is fair. Recent evidence has suggested ciency. Severe VUR function, renal scarring,  that imaging work-ups for children with a first uncom- has been associ- hypertension, or end-stage  plicated UTI may not improve patient care. In one pro- ated with recurrent spective study,24 renal ultrasonography did not change UTI and recur- 30 renal disease. the management of UTI in any of 255 children younger rent pyelonephri- than five years who were admitted with a first uncom- tis,31 but the association of VUR with renal scarring has plicated febrile UTI. An earlier systematic review25 of been inconsistent.32,33 Renal scarring is associated with 63 descriptive studies found no evidence of the impact of recurrent UTI32 and recurrent pyelonephritis,34 but a routine imaging on clinical outcomes in children with a causal relationship has not been established.25 first UTI. Although imaging traditionally has been recom- In a randomized trial,26 150 children two to 10 years mended in children with recurrent UTI, no randomized of age with a first UTI were assigned to routine imaging trials are available to support or refute these recommen- (i.e., ultrasonography and voiding cystourethrography dations. Bladder ultrasonography to determine postvoid [VCUG]) or to selective imaging (only if recurrent UTI residual volume may identify urinary obstruction, and or persistent problems were present). Approximately children with renal scarring may benefit from follow-up one in five children (21 percent) in the selective imag- for early detection of hypertension or renal insufficiency, ing group had imaging performed. Routine imaging but data supporting these approaches are sparse. increased the use of prophylactic antibiotics (28 versus 5 percent) but did not reduce the rate of recurrent UTIs treatment (26 versus 21 percent) or renal scarring at two years Empiric antibiotic therapy (Table 223) is reasonable while (9 versus 9 percent). These results suggest that imaging awaiting culture results if there is a high clinical suspicion is not useful in determining which children might ben- of UTI.23 Subsequently changing antibiotics based on efit from prophylactic antibiotics. reported sensitivities may be unnecessary if clinical reso- Extensive imaging work-up (i.e., ultrasonography and lution occurs. According to the AAP, the child should be renal scan within 72 hours, VCUG at one month, and reevaluated with a repeat urine culture and renal/bladder repeat renal scan at six months) was evaluated in a pro- ultrasonography if clinical improvement does not occur spective study27 of 309 children one to 24 months of age within two days.23 with a first febrile UTI. Results of ultrasonography were The authors of randomized trials35,36 comparing oral normal in 88 percent, and abnormalities did not change and parenteral regimens in children with fever and December 15, 2005 ◆ Volume 72, Number 12 www.aafp.org/afp American Family Physician  2485
  • 4. uti in children positive urine cultures did not find differences in cure rates or speed of improvement. Parenteral antibiotics may table 2 be necessary if vomiting precludes oral administration. Empiric Oral antibiotic therapy   The optimal duration of antibiotic therapy has not for uti in children been established. One-day courses of antibiotics are less effective than longer courses.37 Systematic reviews37-39 of Antibiotic Daily dosage randomized trials comparing shorter and longer courses Amoxicillin 20 to 40 mg per kg in three doses* of antibiotics have had varying results, based in part on Cefixime (Suprax) 8 mg per kg in two doses the inclusion of one-day courses in the analysis. Short Cefpodoxime 10 mg per kg in two doses courses (three to five days) of antibiotics may be as effec- (Vantin) tive as longer courses (seven to 14 days), but this has not Cefprozil (Cefzil) 30 mg per kg in two doses been clearly proved.37-39 Cephalexin (Keflex) 50 to 100 mg per kg in four doses No evidence was found to support a recommendation Loracarbef (Lorabid) 15 to 30 mg per kg in two doses for routine posttreatment urine cultures in children Sulfisoxazole 120 to 150 mg per kg in four doses with UTIs. In one study40 of 364 children hospitalized (Gantrisin) with UTI, 291 (80 percent) had follow-up urine cultures, Trimethoprim/ 6 to 12 mg per kg/30 to 60 mg per none of which was positive. sulfamethoxazole kg in two doses (Bactrim, Septra) prevention UTI = urinary tract infection. In a one-year longitudinal study,41 recurrent symptom- *—Amoxicillin is the first choice for infants younger than two atic UTI occurred in 12 percent of children younger than months. five years presenting to an emergency department with a Adapted with permission from Committee on Quality Improvement, first UTI. Children younger than six months had a higher Subcommittee on Urinary Tract Infection. Practice parameter: the diag- nosis, treatment, and evaluation of the initial urinary tract infection risk of recurrence (18.6 percent). in febrile infants and young children [published corrections appear in Prophylactic antibiotics may reduce the risk of recur- Pediatrics 2000;105:141, 1999;103:1052, and 1999;104:118]. Pediat- rent UTI. Two systematic reviews42,43 found weak evidence rics 1999;103:848. of benefit with poor quality trials. Table 323 describes potential prophylactic regimens in children younger than two years. Only one comparison trial of antibiotic because of side effects (number needed to treat to selection was found. In this six-month trial,44 nitrofuran- harm = 5.3), which were mainly gastrointestinal. toin (Furadantin) was more effective than trimethoprim Because VUR has been considered a predisposing fac- (Primsol) in preventing UTIs (number needed to treat tor to UTI and its complications, treatments for children [NNT] = 5.4) but was more likely to be discontinued with VUR have been promoted. Medical management often has used prophylactic antibiotics, but the system- atic reviews43 suggesting that prophylactic antibiotics the authors prevent recurrent UTI did not include studies of children BRIAN S. ALPER, M.D., M.S.P.H., is a research assistant professor with VUR. Nonetheless, the AAP recommends prophy- in the Department of Family and Community Medicine at the laxis until imaging studies are completed and until University of Missouri–Columbia School of Medicine. Dr. Alper also additional treatment based on the imaging findings is is editor-in-chief of DynaMed. Dr. Alper received his medical degree from the Hahnemann University School of Medicine, Philadelphia. instituted.23 Two systematic reviews45,46 of randomized He completed a family medicine residency at Pennsylvania State trials comparing surgical and medical management of University/Good Samaritan Hospital in Lebanon, and a family VUR found no significant differences in UTI recurrence medicine faculty development fellowship at the University of rates, renal function, renal scarring, hypertension, or Missouri–Columbia. end-stage renal disease. In two randomized trials47,48 SARAH H. CURRY, M.D., is a resident in the University of Missouri– involving more than 400 children younger than 11 years Columbia Family and Community Medicine residency program. who had grade III or IV VUR and documented UTI, Dr. Curry received her medical degree from the University of surgery reduced the rate of acute pyelonephritis (21 to Missouri–Columbia School of Medicine. 22 percent incidence with surgery versus 8 to 10 percent Address correspondence to Brian S. Alper, M.D., M.S.P.H., with antibiotic prophylaxis alone; NNT = 7 to 9), but DynaMed LLC, 10 Estes St., Ipswich, MA 01938 (e-mail: editor@ overall rates of UTI did not differ. A new treatment dynamicmedical.com). Reprints are not available from the authors. for children with VUR, dextranomer/hyaluronic acid 2486  American Family Physician www.aafp.org/afp Volume 72, Number 12 ◆ December 15, 2005
  • 5. uti in children Data sources: Online sources including PubMed, The table 3 Cochrane Library, Clinical Evidence, DynaMed, and antibiotic choices for uti prophylaxis   the National Guideline Clearinghouse were searched in in children April 2003 using “urinary tract infection” and age limi- tations (younger than 18 years) where applicable. Refer- Antibiotic Dosage ence lists of retrieved articles and reviews also were used. Methenamine mandelate 75 mg per kg per day The highest level of evidence found for each specific (Mandelamine) in two doses topic was included. This review is based on a more thor- Nalidixic acid (NegGram) 30 mg per kg per day ough version of this topic that is available in DynaMed in two doses (http://www.DynamicMedical.com) and is updated as Nitrofurantoin (Furadantin) 1 to 2 mg per kg once per day additional relevant information is identified.53 Sulfisoxazole (Gantrisin) 10 to 20 mg per kg per day in two doses The authors would like to thank J. Lynn Teague, M.D., F.A.A.P., Associate Trimethoprim/ 2 mg per kg/10 mg Professor of Clinical Surgery, Urology and Child Health, University of sulfamethoxazole per kg nightly Missouri–Columbia, for clinical and editorial feedback and for providing (Bactrim, Septra) expert recommendations. or 5 mg per kg/25 mg Author disclosure: Dr. Alper is editor-in-chief of DynaMed. per kg twice per week UTI = urinary tract infection. rEFErEncEs Adapted with permission from Committee on Quality Improvement, 1. Marild S, Jodal U. Incidence rate of first-time symptomatic urinary tract Subcommittee on Urinary Tract Infection. Practice parameter: the diag- infection in children under 6 years of age. Acta Paediatr 1998;87: nosis, treatment, and evaluation of the initial urinary tract infection in 549-52. febrile infants and young children [published corrections appear in Pedi- 2. Bachur R, Harper MB. Reliability of the urinalysis for predicting urinary atrics 2000;105:141, 1999;103:1052, and 1999;104:118]. Pediatrics tract infections in young febrile children. Arch Pediatr Adolesc Med 1999;103:849. 2001;155:60-5. 3. Twaij M. Urinary tract infection in children: a review of its pathogenesis and risk factors. J R Soc Health 2000;120:220-6. copolymer (Deflux), is a bulking agent placed endo- 4. Loening-Baucke V. Urinary incontinence and urinary tract infection and their resolution with treatment of chronic constipation of childhood. scopically near the distal ureteral orifice. Deflux was Pediatrics 1997;100:228-32. more effective than antibiotic prophylaxis in resolving 5. Koff SA, Wagner TT, Jayanthi VR. The relationship among dysfunctional childhood VUR in one randomized trial49 of 61 children elimination syndromes, primary vesicoureteral reflux and urinary tract infections in children. J Urol 1998;160:1019-22. but did not prevent UTI. Nine UTIs were recorded in six 6. Shaikh N, Hoberman A, Wise B, Kurs-Lasky M, Kearney D, Naylor S, of the 40 children in the Deflux group, whereas none et al. Dysfunctional elimination syndrome: is it related to urinary tract occurred in the 21 children receiving antibiotics.49 infection or vesicoureteral reflux diagnosed early in life? Pediatrics Cranberry juice and related products have not been 2003;112:1134-7. shown to prevent or reduce UTI in children; in a sys- 7. Struthers S, Scanlon J, Parker K, Goddard J, Hallett R. Parental report- ing of smelly urine and urinary tract infection. Arch Dis Child 2003;88: tematic review50 of seven trials, the evidence base was 250-2. too limited to support such conclusions. 8. Labbe J. Self-induced urinary tract infection in school-age boys. Pediat- Circumcision prevented recurrent symptomatic UTI rics 1990;86:703-6. in one randomized trial.51 Seventy uncircumcised boys 9. Hellerstein S. Recurrent urinary tract infections in children. Pediatr Infect Dis 1982;1:271-81. three months to 10 years of age with a first symptomatic 10. Pollack CV Jr, Pollack ES, Andrew ME. Suprapubic bladder aspiration culture-confirmed UTI were randomized to immediate versus urethral catheterization in ill infants: success, efficiency and circumcision or circumcision after six months. Recur- complication rates. Ann Emerg Med 1994;23:225-30. rent symptomatic UTIs developed in three of 35 boys 11. Liaw LC, Nayar DM, Pedler SJ, Coulthard MG. Home collection of urine for culture from infants by three methods: survey of parents’ prefer- during the six-month delay (8.6 percent) but not in ences and bacterial contamination rates. BMJ 2000;320:1312-3. the boys who received immediate circumcision (NNT 12. Ramage IJ, Chapman JP, Hollman AS, Elabassi M, McColl JH, Beat- = 12). Circumcision may provide primary preven- tie TJ. Accuracy of clean-catch urine collection in infancy. J Pediatr tion of UTI in boys, based on prospective follow-up of 1999;135:765-7. 69,100 boys for two to three years.52 However, circum- 13. Bulloch B, Bausher JC, Pomerantz WJ, Connors JM, Mahabee-Gittens M, Dowd MD. Can urine clarity exclude the diagnosis of urinary tract cision may not be warranted for this specific purpose infection? Pediatrics 2000;106:E60. because 195 circumcisions would be needed to prevent 14. Gorelick MH, Shaw KN. Screening tests for urinary tract infection in one hospital admission for UTI in the first year of life. children: a meta-analysis. Pediatrics 1999;104:E54. December 15, 2005 ◆ Volume 72, Number 12 www.aafp.org/afp American Family Physician  2487
  • 6. uti in children 15. Rawal K, Senguttuvan P, Morris M, Chantler C, Simmons NA. Signifi- 36. Baker PC, Nelson DS, Schunk JE. The addition of ceftriaxone to oral cance of crystal clear urine. Lancet 1990;335:1228. therapy does not improve outcome in febrile children with urinary tract 16. Tremblay S, Labbe J. Crystal-clear urine and infection. Lancet 1994;343: infections. Arch Pediatr Adolesc Med 2001;155:135-9. 479-80. 37. Keren R, Chan E. A meta-analysis of randomized, controlled trials 17. Huicho L, Campos-Sanchez M, Alamo C. Metaanalysis of urine screen- comparing short- and long-course antibiotic therapy for urinary tract ing tests for determining the risk of urinary tract infection in children. infections in children. Pediatrics 2002;109:E70. Pediatr Infect Dis J 2002;21:1-11. 38. Michael M, Hodson EM, Craig JC, Martin S, Moyer VA. Short versus 18. Hoberman A, Chao HP, Keller DM, Hickey R, Davis HW, Ellis D. Prevalence standard duration oral antibiotic therapy for acute urinary tract infec- of urinary tract infection in febrile infants. J Pediatr 1993;123:17-23. tion in children. Cochrane Database Syst Rev 2004;(4):CD003966. 19. Crain EF, Gershel JC. Urinary tract infections in febrile infants younger 39. Tran D, Muchant DG, Aronoff SC. Short-course versus conventional than 8 weeks of age. Pediatrics 1990;86:363-7. length antimicrobial therapy for uncomplicated lower urinary tract infections in children: a meta-analysis of 1279 patients. J Pediatr 20. Shaw KN, McGowan KL, Gorelick MH, Schwartz JS. Screening for uri- 2001;139:93-9. nary tract infection in infants in the emergency department: which test is best? Pediatrics 1998;101:E1. 40. Currie ML, Mitz L, Raasch CS, Greenbaum LA. Follow-up urine cultures and fever in children with urinary tract infection. Arch Pediatr Adolesc 21. Pitetti RD, Choi S. Utility of blood cultures in febrile children with UTI. Med 2003;157:1237-40. Am J Emerg Med 2002;20:271-4. 41. Panaretto K, Craig J, Knight J, Howman-Giles R, Sureshkumar P, Roy L. 22. Bachur R, Caputo GL. Bacteremia and meningitis among infants with Risk factors for recurrent urinary tract infection in preschool children. J urinary tract infections. Pediatr Emerg Care 1995;11:280-4. Paediatr Child Health 1999;35:454-9. 23. Committee on Quality Improvement, Subcommittee on Urinary Tract 42. Williams GJ, Lee A, Craig JC. Long-term antibiotics for preventing recur- Infection. Practice parameter: the diagnosis, treatment, and evalua- rent urinary tract infection in children. Cochrane Database Syst Rev tion of the initial urinary tract infection in febrile infants and young 2004;(4):CD001534. children. [published corrections appear in Pediatrics 2000;105:141, 1999;103:1052, and 1999;104:118]. Pediatrics 1999;103:843-52. 43. Le Saux N, Pham B, Moher D. Evaluating the benefits of antimicrobial prophylaxis to prevent urinary tract infections in children: a systematic 24. Zamir G, Sakran W, Horowitz Y, Koren A, Miron D. Urinary tract infec- review. CMAJ 2000;163:523-9. tion: is there a need for routine renal ultrasonography? Arch Dis Child 2004;89:466-8. 44. Brendstrup L, Hjelt K, Petersen KE, Petersen S, Andersen EA, Daugbjerg PS, et al. Nitrofurantoin versus trimethoprim prophylaxis in recurrent 25. Dick PT, Feldman W. Routine diagnostic imaging for childhood urinary urinary tract infection in children. A randomized, double-blind study. tract infections: a systematic overview. J Pediatr 1996;128:15-22. Acta Paediatr Scand 1990;79:1225-34. 26. Dick PT. Annual Meeting of Canadian Pediatric Society, June 12-16, 45. Jodal U, Hansson S, Hjalmas K. Medical or surgical management for 2002. Pediatric Notes 2002;26(27):105. children with vesico-ureteral reflux? Acta Paediatr Suppl 1999;88: 27. 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Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, et Last reviewed September 6, 2005. Accessed online September 15, al. Oral versus initial intravenous therapy for urinary tract infections in 2005, at: http://www.DynamicMedical.com. young febrile children. Pediatrics 1999;104:79-86. 2488  American Family Physician www.aafp.org/afp Volume 72, Number 12 ◆ December 15, 2005