Urinary tract infections in neonates

Author:Donough J O'Donovan, MD
This topic last updated: Feb 08, 2018.

INTRODUC Febrile term infants —rates of UTI vary from 7 to 15 percent. UTI typically
TION & presents in the 2nd or 3 rd weeks postnatally. The incidence of UTI is low (<2 %) in
EPIDEMIOL the first few days of life even in neonates who are bacteremic.
OGY Preterm infants — risk increases with decreasing gestational age & birth
weight,& ELBW have greater risk
MICROBIOL Term infants — community-acquired UTI, Escherichia coli is the most common ( 80
OGY percent of infections) .
Other gram-negative causes include Klebsiella, Proteus, Enterobacter, &Citrobacter.
Gram-positive pathogens -Staphylococcus coagulase-negative species, Enterococcus, &
rarely, Staphylococcus aureus.
Preterm infants — Coagulase-negative Staphylococcus and Klebsiella are more likely
causes of UTI in hospitalized preterm infants, and E. coli is less commonly seen]. Candida
species are also frequent pathogens in preterm infants, particularly in ELBW s
PATHOGEN Term infants — Most UTIs is upper tract infection (pyelonephritis) rather than
ESIS simple cystitis. UTI in term infants is primarily due to ascending infection rather
than hematogenous spread from a remote source. Several virulence factors in E.
coli (esp adhesins )account for the propensity of this organism to cause UTI,
especially when the urinary tract is anatomically normal.
Preterm infants — Hematogenous infection likely, as there is a higher
concordance rate of sepsis than in term infants.
HOST FACTORS
1. Male infants — increased risk due to increased urinary tract
malformations
2. Uncircumcised males — 10-fold greater in uncircumcised is related to an
increased rate of bacterial colonization and enhanced bacterial
adherence.
3. Prematurity — higher risk for developing UTI compared with term infants
because of their relatively immunocompromised status and the use of
invasive devices (eg, urinary catheters)
4. Kidney and urinary tract abnormalities- Urinary tract abnormalities may
cause to UTI by mechanisms- inadequate urine flow, incomplete emptying
of the bladder, and incompetent anatomic junctions that permit reflux of
contaminated urine. Differences between males and females in voiding
pressures and residual urine volumes. With maturation, girls have more
UTIs after the first months of life.
Term infants — Abnormalities are seen on ultrasound in 35 -50 % of
neonates (term and preterm) and young infants (<3 months of age) with
UTI. The most common findings are pelviectasis and mild hydronephrosis.
Major renal or urologic abnormalities (ie, high
grade hydronephrosis/vesicoureteral reflux [VUR] and/ other important
 structural abnormalities) are found in approximately 5 to 10 percent of
infants
Preterm infants — The prevalence of renal or urologic abnormalities
similar in preterm infants compared with term. (35 to 40 %). The most
common findings were pelviectasis and mild hydronephrosis. Major
findings were seen in 5 percent of patients and included high
grade hydronephrosis/VUR, renal dysplasia, unilateral agenesis, partial
duplication of the collecting system, and horseshoe kidney.
Other kidney and urinary tract abnormalities associated with neonatal UTI
include:
a) Urinary obstructive lesions (eg, ureteropelvic junction or ureterovesical
junction obstruction, posterior urethral valves)
b) Ectopic ureter
c) Renal parenchymal disorders (eg, polycystic diseases, renal dysplasia)
CLINICAL Term infants — The signs and symptoms of UTI in neonates are nonspecific.
FEATURES Infants can have lethargy, irritability, tachypnea, or cyanosis, and may appear
acutely ill.The most common clinical findings are:
 Fever (20 - 40 %)
 Failure to thrive (15- 43 %)
 Jaundice (3 - 41 %)
 Vomiting (9 - 41 %)
 Loose stools (3 -5 %)
 Poor feeding (3 - 5 %)
The hyperbilirubinemia that occurs with UTI typically is conjugated and related to
cholestasis and is often seen after 1 week of age& may be the first sign of UTI in
some infants.
Other less common findings include abdominal distension resulting from ileus or
enlarged kidneys due to hydronephrosis.
UTI may be the presenting manifestation that identifies a neonate with an
underlying congenital anomaly of the kidney and urinary tract (CAKUT).
Preterm infants — The clinical manifestations of UTI are similar to those of term
infants, with the addition of apnea and hypoxia..
 Feeding intolerance (62 %)
 Apnea and bradycardia (45 %)
 Lethargy (30 %)
 Tachypnea (30 %)
 Abdominal distension (12 %)
Hypoxia with documented oxygen desaturation (12 %)
Laboratory
tests ,furth
er Urinalysis — A urinalysis includes both a microscopic assessment of a centrifuged
evaluation specimen of urine and a dipstick analysis that includes testing for leukocyte esterase
and DD (marker for pyuria) and nitrite (marker for Enterobacteriaceae). The test
characteristics for dipstick and microscopic urinalysis in young infants are summarized
in the table (table 1) [22].
Urinalysis should always be performed in conjunction with a urine culture to confirm
or exclude the diagnosis of UTI in neonates. Although a positive urinalysis is predictive
of UTI in neonates, the test is not sufficiently sensitive or specific to be used alone to
make the diagnosis
As noted below, the presence of pyuria can be used to support a diagnosis of UTI
when the colony count of a catheterized specimen falls between 10,000 - 50,000
CFU/mL. Pyuria is detected by either microscopic examination of leukocytes on an
unspun urine sample or a positive test for leukocyte esterase. For both tests, the urine
should be obtained by either catheterization or suprapubic aspiration.
Urine culture — Diagnosis of UTI is based upon a positive urine culture from a
specimen of urine that is either collected by bladder catheterization or suprapubic
aspiration (SPA). "Clean voided" bag urine samples should not be used for culture, as
there is a high rate of false positive results. Obtaining a midstream clean catch
specimen in neonates is impractical and unreliable technique as there remains a high
rate of contamination.
A positive result is based on identifying a uropathogenic bacteria and reaching a
threshold of number of colony forming units (CFU) that grow on the culture medium.
The number of CFU defining a positive urine culture varies based on the method of
collection. Urine specimens should be transported on ice and must be processed
expeditiously If cannot then it should be refrigerated.
Urine cultures are not obtained for term infants who are being evaluated for early-
onset sepsis during the first six days of life.
Bladder catheterization — Bladder catheterization is a reliable method for detection
of UTI in neonates. Specimen contamination is more likely with bladder
catheterization than SPA; however, this can be mitigated by discarding the initial
stream and culturing the subsequent urine stream during catheterization.
For samples obtained via bladder catheterization, UTI is generally defined as growth of
a single uropathogenic pathogen with a colony count of ≥50,000 CFU/mL, or a colony
count between 10,000 and 50,000 CFU/mL with associated pyuria detected on
urinalysis.
Suprapubic aspiration — is the most reliable technique to identify bacteriuria; Any
growth of a urinary pathogen is significant. The growth of 1 colony is equivalent to
1000 CFU/mL.
Complete blood count with differential count
Sepsis evaluation — A blood culture should be obtained in all infants in whom UTI is
suspected because of the risk of urosepsis.The risk of concurrent sepsis in neonates
with UTI varies from 4 to 7 percent in term neonates and young infants. In preterm
infants, the risk of urosepsis is greater. (< 26 weeks gestation and mechanically
ventilated). In addition, clinicians should have a low threshold to perform a lumbar
puncture, as approximately 1 - 3 % of neonates with UTI have bacterial meningitis. In
particular, lumbar puncture should be performed in ill-appearing infants or those with
a fever.
DIFFERENTIAL DIAGNOSIS — Because the signs and symptoms of neonatal UTI are
nonspecific , several other disorders may present with similar findings. However, a
positive urine culture differentiates UTI from these conditions:
 ●Other infectious conditions including sepsis and meningitis – Cultures of urine and
other body fluids (eg, blood, cerebrospinal fluid) distinguish UTI from these other
infectious diseases. UTI can occur concomitantly with these other infectious
conditions.
●Inborn errors of metabolism.
Radiographic evaluation — Because of the high prevalence of urinary tract
abnormalities, we perform radiographic evaluation in all neonates with UTI. The first
step of this evaluation is renal ultrasonography to identify structural abnormalities. In
addition, we suggest voiding cystourethrogram (VCUG) to evaluate for vesicoureteral
reflux (VUR) in neonates with abnormal renal ultrasound, non-E. coli pathogen, or
recurrent UTI.
a) Renal ultrasonography — should be obtained after antibiotic treatment is
initiated and the infant's clinical condition has stabilized. Renal
ultrasonography evaluates the size & position of the kidneys and the
appearance of the collecting system, including the size and thickness of the
bladder. Ultrasound can detect dilation of the collecting system, structural
abnormalities (eg, solitary kidney, multicystic dysplasia, duplex collecting
system), and echogenic fungal material or stones. However, a normal
ultrasound examination does not exclude VUR or renal scarring.
b) Voiding cystourethrogram — A VCUG should be performed in neonates with
abnormal ultrasound findings. for most neonates with first-time UTI and
normal renal ultrasound is to "wait and watch." At many institutions, VCUGs
are generally performed only in neonates with abnormal renal ultrasound,
non-E. coli pathogen, or recurrent UTI. Some centers routinely perform VCUGs
in all neonates with first-time febrile UTI If a "wait and watch" approach is
used, patients should be monitored for recurrence (eg, if the infant has a
febrile illness, a urine sample should be obtained to evaluate for UTI). If the
patient develops a subsequent UTI, evaluation with VCUG is appropriate.
c) Other imaging — Renal cortical scintigraphy (with Tc99m-dimercaptocuccinic
acid [DMSA]) may be used to identify renal scarring and acute changes due to
pyelonephritis. It is not generally helpful in the acute setting but may be
obtained as part of follow-up evaluation particularly if renal damage is
suggested by ultrasound. MRI may be required for proper characterization of
renal anomalies
TREATMENT Treatment with intravenous broad-spectrum antimicrobial agents should be initiated as
— soon as cultures of urine, blood, and cerebrospinal fluid (if indicated) have been
obtained.
Choice of agent and dosing
Initial Empiric therapy — The choice and dosing of empiric antibiotic therapy is generally
the same as for the treatment of neonatal sepsis. This is because the causative agents
are similar in neonatal sepsis and UTI, it is difficult to differentiate between the two
based on presentation, and there is risk of concurrent infection.
The combination of parenteral ampicillin and gentamicin provides coverage for the most
common bacterial pathogens. However, with increasing reports of resistant organisms,
local surveillance of pathogens and antibiotic susceptibility patterns may be important to
determine appropriate initial antibiotic therapy.
Recommendations for doses are dependent on the weight and chronologic age of the
infant:
 1. ●Weight >2 kg –
A. For infants >2 kg who are ≤7 days old, Ampicillin - 50 mg/kg per dose
IV q8 hourly and gentamicin - 4 mg/kg / dose IV q 24 hourly.
B. For infants >7 days old, Ampicillin 50 mg/kg /dose IV q 6 hourly &
gentamicin dosing is the same as in younger neonates.
2. ●Weight ≤2 kg –
A. For infants <2 kg who are ≤7 days old Ampicillin - 50 mg/kg / dose IV
q12 hourly and gentamicin is 5 mg/kg/ dose IVq 48 hourly.
B. For infants >7 days old with community-acquired UTI, Ampicillin -
50 mg/kg /dose IV q 8 hourly and gentamicin 5 mg/kg /dose IV q 36
hourly. However, most late UTIs in low birth weight neonates are
hospital-acquired, and vancomycin is suggested rather than ampicillin.

The choice of empiric regimen also depends on the clinical setting:

 For hospital-acquired infections, vancomycin is substituted

for ampicillin since the predominant organisms include coagulase-
negative staphylococci, Staphylococcus aureus,
and Enterococcus species.
 If meningitis is also suspected, higher doses of antibiotics must be
used. In infants >7 days old, a third generation cephalosporin
(eg, cefotaxime, if available) is added, pending culture results
Organism-specific therapy — Antimicrobial therapy is altered based upon the isolation
of a pathogen, its pattern of antimicrobial susceptibility, and if there are concurrent
infections (eg, sepsis or meningitis).
Response to therapy — Sterilization of the urine should occur within 48 hours of
treatment with the appropriate antimicrobial agent. Optimally, it should be confirmed by
repeating the urine culture at that time. If bacteriuria persists despite appropriate
therapy, the urinary tract and other sites should be investigated to determine a potential
reservoir of infection.
Duration of therapy — The optimal duration of treatment for neonatal UTI is uncertain
and decisions are based on clinical judgement and experience. In most centers, the
duration of antibiotic therapy is 10 -14 days for neonates with uncomplicated bacterial
UTI. It is desirable complete the treatment course in neonates with a course of
intravenous antibiotics, although older infants with uncomplicated UTIs can be switched
to oral antibiotics after clinical improvement based on the judgement of the individual
clinician. Longer treatment is often needed for fungal infections.
In most centers, antibiotic prophylaxis with low-dose orally administered amoxicillin (15
to 20 mg/kg per day) is started until radiographic evaluation has been performed to
detect urinary tract abnormalities. Continuation of this prophylaxis depends upon the
results of imaging studies.
PROGNOSI It has been challenging to determine the prognosis of neonatal UTI as there are
S— confounding factors (underlying kidney and urinary tract abnormalities) and a paucity of
long-term outcome studies in neonates. Indirect evidence from studies show that infants
< 1 year of age are at greater risk for renal scarring than older patients. In addition,
 children with vesicoureteral reflux are more likely to have evidence of renal scarring.
Renal parenchymal scarring is associated with an increased risk for hypertension and
chronic kidney disease.
Neonatal UTI may impair renal growth,although renal size tends to become normal
later.
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3. Lin DS, Huang SH, Lin CC, et al. Urinary tract infection in febrile infants
younger than eight weeks of Age. Pediatrics 2000; 105:E20.
4. Riskin A, Toropine A, Bader D, et al. Is it justified to include urine cultures
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