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Clinical Pediatrics

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Diagnosis and Management of Urinary Tract Infections in Neonates and Young Infants
Jonathan D Santoro, Vanessa G Carroll and Russell W Steele
CLIN PEDIATR 2013 52: 111
DOI: 10.1177/0009922812471713

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Commentary
Clinical Pediatrics

Diagnosis and Management of Urinary 52(2) 111­–114


© The Author(s) 2012
Reprints and permission:
Tract Infections in Neonates and Young sagepub.com/journalsPermissions.nav
DOI: 10.1177/0009922812471713

Infants
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Jonathan D. Santoro, MD1,Vanessa G. Carroll, MD1,


and Russell W. Steele, MD1

Introduction patient population. Additionally, some experts feel that


these criteria could be used to lower the age threshold
The American Academy of Pediatrics (AAP) recently for immediate hospitalization to less than 28 days, as is
issued guidelines for the diagnosis and management of recommended by several institutions.10
urinary tract infections (UTIs) in children 2 months to 2
years of age.1 This publication, however, did not address
the management of younger infants and neonates with UTIs in Young Infants
suspected or documented UTIs. Among neonates and young infants presenting with
febrile illness in the first few weeks of life, UTI is the
most commonly diagnosed serious bacterial infection,
Neonates With Fever with incidence as high as 7.5% in various reports.11
Neonates 28 days of age or less with fever routinely Because it is so common, many studies have examined
undergo a sepsis workup, which should include 2 blood potential risk factors for UTIs. A major risk factor in this
cultures, complete blood count with differential, cere- population is male gender. This is surprising, given that
brospinal fluid analysis, urinalysis, and urine culture. UTIs are much more common in girls later in infancy
This recommendation has been supported by a large and childhood. Others include prematurity, a tempera-
number of clinical studies.2-4 Patients are then typically ture greater than 102°F, and white race. The greatest risk
hospitalized and begun on empirical antibiotics pending factor for boys is lack of circumcision, which has been
results of the cultures. There is therefore little need for reported to increase the risk of UTIs by nearly 10-fold.11
risk assessment prior to hospitalization and treatment in In pediatric patients 29 to 60 days of age, diagnosis
this age range. However, a definition of UTI based on and management of suspected UTIs are problematic pri-
the presence of pyuria, colony count of the urine cul- marily because, as with neonates, the definition of a UTI
ture, or other criteria has not been established for neo- has not been established. Criteria proposed in the recent
nates. guidelines for older infants and children do not apply to
these patients because literature reviewed for this publi-
cation did not include this age group.1 Pediatricians,
Young Infants With Fever therefore, must use empirical criteria for the diagnosis
Several publications have made recommendations for and management of these febrile patients when there is
the diagnostic and therapeutic management of febrile no evidence of pyuria or when urine cultures have fewer
infants from 29 days, to 56 to 60 days of age referred to than 50 000 colonies/mL. If criteria for older infants are
as the Philadelphia, Boston, Milwaukee, and Rochester fulfilled, that is, there is evidence of pyuria plus a bacte-
protocols.5-8 The use of laboratory-based stratification rial culture with a single organism colony count >50
in these high-risk young infants is critical for identify- 000/mL, decisions are obviously easier.
ing at-risk patients because physical examination alone
has been shown to be quite insensitive.6,7,9 The criteria 1
Ochsner Children’s Health Center and Tulane University School of
established at the Children’s Hospital of Philadelphia5 Medicine, New Orleans, LA, USA
stratified infants between the ages of 29 and 60 days of
Corresponding Author:
age into categories at low and high risk for developing
Jonathan Santoro, Department of Pediatrics, Ochsner Children’s
a serious bacterial infection (Table 1). This criterion set Health Center and Tulane University School of Medicine, 4207
reported a sensitivity of 98% and negative predictive Fontainebleau Drive, New Orleans, LA 70125, USA
value of 99.7%, which is excellent for this vulnerable Email: jsantoro@tulane.edu

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112 Clinical Pediatrics 52(2)

Table 1. Boston, Milwaukee, Philadelphia, and Rochester Criteria for Risk Stratification in Febrile Infants Between 29 and 89
Days of Age; All Patients Have Otherwise Unremarkable Physical Examinations

Boston Criteria Milwaukee Criteria Philadelphia Criteria Rochester Criteria


Age range 28-89 Days 28-56 Days 29-60 Days ≤60 Days
Temperature ≥38.0°C ≥38.0°C ≥38.2°C ≥38.0°C
Medical history No recent immunizations ND ND Term infant
or antibiotics in last
48 hours
  Not dehydrated No perinatal antibiotics
  No underlying disease
  Not hospitalized longer
than mother
Laboratory findings CSF <10/mm3 CSF <10/mm3 CSF <8/mm3 WBC >5000 and <15
000/mm3
  WBC < 20 000/mm3 WBC < 15 000/mm3 WBC < 15 000/mm3 ABC < 1500
  UA <10 WBC/hpf UA <5-10 WBC/hpf UA <10 WBC/hpf UA ≤ 10 WBC/hpf
without bacteria and
negative leukocyte
esterase
  CXR: no infiltrate CXR: no infiltrate Urine Gram stain Stool: WBC ≤ 5/hpf on
if taken if taken negative smear when indicated
  CSF Gram stain negative  
  CXR: no infiltrate  
  Stool: no blood with few  
or no WBC on smear
  Band-neutrophil ratio  
<0.2
Management for low risk Outpatient follow-up Outpatient follow-up Outpatient follow-up Outpatient follow-up
with oral empirical within 24 hours and IM without antibiotics without antibiotics
antibiotics ceftriaxone 50 mg/kg
Management for high risk Hospitalize and ND Hospitalize and Hospitalize and
administer empirical administer empiric administer empirical
antibiotics antibiotics antibiotics

Abbreviations: ND, not defined; CSF, cerebrospinal fluid; WBC, white blood cell count; hpf, high-power field; UA, urinalysis; CXR, chest X-ray;
ABC, absolute band count; IM, intramuscular.

Risk of UTI a renal ultrasound and another 2% of patients who had


a follow-up voiding cystourethrogram.13,14
The AAP guidelines for UTI management in infants
older than 60 days use a calculated percentage likeli-
hood of UTI based on risk factors.1 Physicians must Laboratory Diagnosis of UTI
first decide what probability of infection, <1%, 1% to Laboratory diagnosis of UTI in children less than 60
2%, or >2%, warrants more extensive evaluation and days of age should take into account both evidence of
perhaps empirical therapy prior to culture results being pyuria and documentation of bacteriuria. Most clinical
available (Table 2). Such guidelines for younger patients laboratories report white blood cells (WBCs) in urine
may not be acceptable because of the higher morbidity as the average number per high-power field (hpf) of
in infants younger than 60 days of age. Most important, centrifuged urine. With this methodology, pyuria is
with delayed diagnosis and treatment of UTIs, bactere- generally defined as 5 or more WBCs/hpf. Several
mia is known to occur in 21% to 36% of cases.12 studies have demonstrated that in patients less than 8
Moreover, these children are more likely to have ana- weeks of age, the sensitivity of this standard urinalysis
tomical defects. In a recent study of children less than 2 in predicting UTI (defined with a positive culture) is as
months old with a UTI, the incidence of major ana- low as 30%, which is significantly lower than what is
tomical abnormalities was found in 4% of patients with reported in older infants.15

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Santoro et al 113

Table 2. Current AAP Guidelines for Probability of UTI Development in Febrile Infants1

Individual Risk Factors: Girls Individual Risk Factors: Boys  


White race Nonblack race  
Temperature ≥ 39.0°C Temperature ≥ 39.0°C  
Fever ≥ 2 days Fever ≥ 24 hours  
Absence of another source of infection Absence of another source of infection  
Age < 12 months  
Probability of UTI (Girls) Number of Factors Present  
<1% No more than 1 factor  
<2% No more than 2 factors  

Probability of UTI (boys) Factors if Uncircumcised Factors if Circumcised


<1% a No more than 2
<2% None No more than 3

Abbreviations: AAP, American Academy of Pediatrics; UTI, urinary tract infection.

Another methodology generally referred to as an mL hypothetically increases sensitivity but lowers


“enhanced urinalysis” utilizes uncentrifuged urine and specificity, yet studies reported no change in the diag-
a counting chamber, reporting WBCs as the average nosis of UTI.11 Urine bacterial counts between 10 000
number per microliter. Most investigators use 10 or and 50 000 CFU/mL have previously demonstrated a
more WBCs/µL to define pyuria. This enhanced uri- high likelihood of asymptomatic bacteriuria when used
nalysis reduces the variability of results by avoiding the alone as diagnostic criteria for UTI.11 Although unstud-
concentration and resuspension of solid elements ied, adding the additional condition of 10 WBC/µL to
required when small samples are centrifuged. Using diagnostic criteria would theoretically decrease the
this methodology in older age groups and defining a detection of lone asymptomatic bacteriuria while
UTI as bacterial colony counts of >50 000 colony form- increasing the recognition of UTI in this patient
ing units (CFUs)/mL, sensitivity improved to 84.5% population.
with a positive predictive value of 93.1%.15 Thus, many Contamination of cultures and asymptomatic bacte-
experts conclude that in febrile infants less than 8 weeks riuria are additional factors that complicate a clear
of age, hemocytometer WBC counts should be used diagnosis of UTI. Asymptomatic bacteriuria of course
along with urine culture to diagnose UTI.15-17 does not require treatment. To reduce the likelihood of
The low yield of standard urinalysis in this age group contamination, catheterization or suprapubic aspiration
has led to examination of other laboratory studies that to obtain urine cultures are mandatory in all infants and
may help diagnose UTI in infants younger than 60 days. neonates.19,20
Lin et al15 determined that a CRP (C-reactive protein)
of >20 and ESR (erythrocyte sedimentation rate) >30
were clinically significant predictive factors for UTI, Conclusion
but a WBC count >15 000/µL was not. Although the Clinical and laboratory assessment of possible UTIs in
specificities of elevated CRP and ESR were high (90% neonates and young febrile infants is complex. Although
and 78%, respectively), their sensitivities were lower rates of confounding factors range greatly across hospi-
than desired (59% and 73%, respectively), indicating tals, geography, and gender, in a population with such a
that they are limited as predictors for identifying UTI in high risk for bacteremia and renal damage, a conserva-
this population. tive definition of UTI is warranted.
If the urine WBC count is not taken into consider- The current standard of care for neonates, which
ation and only a urine bacterial colony count of >100 includes hospitalization and a workup for sepsis should
000 CFU/mL is used to define UTI, it is estimated that be maintained. Beyond the neonatal age range, clinical
approximately 20% of true UTIs would be missed.18 A and laboratory criteria can be used to make decisions for
lower bacterial count is, therefore, favored given the inpatient or outpatient management. For neonates and
risks associated with a false negative diagnosis. Using infants younger than 60 days of age, we suggest the fol-
a cutoff bacterial colony count as low as 10 000 CFU/ lowing criteria to define a UTI:

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114 Clinical Pediatrics 52(2)

1. Pyuria as determined with an “enhanced uri- infection although hospitalized for suspected sepsis. J
nalysis” (hemocytometer counting chamber) Pediatr.1985;107:855-860.
of ≥10 WBC/µL 7. Bonadio WA, Hagen E, Rucka J, Shallow K, Stommel P,
2. A urine culture colony count of ≥10 000 CFU/ Smith D. Efficacy of a protocol to distinguish risk of seri-
mL for a single organism ous bacterial infection in the outpatient evaluation of febrile
young infants. Clin Pediatr (Phila). 1993;32:401-404.
Finally, selection of antibiotics is based on the sus- 8. Baskin M, O’Rourke E, Fleisher G. Outpatient treatment
ceptibility pattern of the organism, and duration of of febrile infants 28 to 89 days of age with intramuscular
therapy is the same as with older infants, that is, 7 to 14 administration of ceftriaxone. J Pediatr. 1992;120:22-27.
days. All these young patients should also undergo renal 9. Lee GM, Harper MB. Risk of bacteremia for febrile young
and bladder ultrasonography and voiding cystoure- children in the post-Haemophilus influenzae type b era.
thrography to assess for genitourinary abnormalities, Arch Pediatr Adolesc Med. 1998;152:624-628.
given the correlation of these abnormalities with UTI in 10. Condra C, Parbhu B, Lorenz D, Herr S. Charges and com-
this age group. plications associated with the medical evaluation of febrile
young infants. Pediatr Emerg Care. 2010;26:186-191.
Declaration of Conflicting Interests 11. Zorc JJ, Levine DA, Platt SL, et al. Clinical and demo-
The authors declared no potential conflicts of interest with graphic factors associated with urinary tract infection in
respect to the research, authorship, and/or publication of this young febrile infants. Pediatrics. 2005;116:644-648.
article. 12. Bachur R, Caputo GL. Bacteremia and meningitis among
infants with urinary tract infections. Pediatr Emerg Care.
Funding 1995;11:280-284.
The authors received no financial support for the research, 13. Nowell L, Moran C, Smith PB, et al. Prevalence of renal
authorship, and/or publication of this article. anomalies after urinary tract infections in hospitalized
infants less than 2 months of age. J Perinatol. 2010;30:
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