Urinary Tract Infection

I. Definition:

A urinary tract infection (UTI) is the presence of pathogenic bacteria or

fungus in the urinary tract. It is the most common bacterial infection in febrile
neonates, although it is very uncommon in the first few days of life

II. Incidence:

In febrile children less than 2 months of age without an obvious source

of infection,
the prevalence of UTI is 5% to 20%.8–10 There is a male predominance
in the neonatal period,

II. Pathophysiology.

the most common pathogens isolated in neonatal UTI.

Nosocomial infections occur more often due to indwelling urinary
catheters.

A. Term infants.

Ascending infection through the urethra is the most common source

of infection in term infants. Escherichia coli is the most common bacterial
pathogen, followed by other gram-negative bacilli (Klebsiella, Proteus,
Enterobacter).
 B. Preterm infants.

Hematogenous spread of infection plays a bigger role in preterm infants.

Klebsiella and coagulase-negative Staphylococcus are more commonly
identified than E coli. Candida UTIs are also common in this group.

C. Fungal urinary tract infections.

Most often caused by Candida species and are more common in

nosocomial infections. Fungal UTIs are also more common in extremely
low birthweight babies.

Bacteriology

Neonatal UTIs are commonly caused by gram-negative rods, with E. coli

(40% to 72%) and Klebsiella species (7% to 40%) responsible for over 80
% of cases.39,40 Enterococcus, a gram-positive coccus, is the third most
common organism,

with an incidence of 10% to 16%.3,35 It is hypothesized that the

incompletely developed neonatal immune system not only increases the
newborn’s risk of infection but also makes the newborn susceptible to
additional organisms compared to older children.41 In neonates with
UTIs, group B streptococci have been found to be more common than in
older children.
Additionally, other gram-positive bacteria, such as coagulase-negative
staphylococci, have been associated with UTIs in premature infants,
although this remains controversial.

Candida, as a causative agent for UTIs, has a reported incidence of 25%

to 42% in premature children admitted to the neonatal intensive care unit.
44,45
 Innate Immunity

Despite its proximity to fecal flora, the urinary tract, with the exception
of urethral meatus, is usually sterile.

The precise mechanism by which the urinary tract maintains sterility is

not well understood. A recent study has shown that ribonuclease 7
(RNase 7) is a novel antimicrobial peptide that is expressed in the
human urinary tract and plays an important role in the innate immunity of
the human uroepithelium .

Agent Virulence

****The most common bacteria infecting the urinary tract are usually
Escherichia coli . The bacterial fimbriae mediate adherence to epithelial cells
of the urinary tract and also cause agglutination of P-type red blood cells .
Both these properties are important for bacterial virulence.

****The red blood cell agglutination can be blocked by sugars like mannose;
therefore , mannose -resistant E. coli are more virulent than those that are
mannose sensitive and predominate as pyelonephritogenic strains .
Mannose resistance is mediated by P-fimbriae that recognizes speci fic
carbohydrate receptors (Gal 1–4 Gal ) on the uroepithelium and can cause
ascending infection in the absence of VUR [ 34 ].

****K antigen is a capsular polysaccharide covering bacteria that shields them

from phagocytosis and exists in greater quantities in pyelonephritogenic strains
.. The fecal carriage of P-fi mbriated E. coli was also higher in children who
were P-1 blood group positive (88 %) than those with P-2 blood group (40 %).

****However, in the presence of VUR, P-fimbriated E. coli is not necessary for

infection of the upper urinary tract. Other virulence factors from uropathogenic
E. coli include the release of alpha hemolysin and cytotoxic necrotizing factor-1
,29–31 as well as the ability to form a protective glycosylated polysaccharide
capsule

 

Table 152–1. COMMON ORGANISMS ISOLATED IN NEWBORN AND

NEONATAL UTI

Organism Incidence (%)

 
Gram-negative rods
 
E. coli 40–72
 
 
 
7–40
Klebsiella spp

Enterobacter cloacae
 3–8
 
Proteus vulgaris   3
 

Serratia marcescens 1–7

Pseudomonas aeruginosa 1

Gram-positive  cocci

10–16
Enterococcus spp
 

Staphylococcus aureus 1–5
 

 
Group B streptococcus 1–3

Staphylococcus, coagulase negative 1
 

 
Viridans streptococcus 1

 
Yeast

25–42
Candida spp
 

Reproduced with permission from Arshad M, Seed PC: Urinary tract infections
in the infant, Clin Perinatol. 2015 Mar;42(1):17-28.  

Gomella_Sec07_p1115_1224.indd 1208 18/10/19 3:19 pm
 IV. Risk factors

A. Congenital anomalies of the kidney and urinary tract (CAKUT)

such as urinary tract dilatation (eg, ureteropelvic junction obstruction,

ureterovesical junction obstructions, ureterocele, ectopic ureter), posterior
urethral valves, and vesicoureteral reflux can predispose to UTIs.

B. Alteration in normal bladder function (eg, neurogenic bladder)

predisposes the infant to UTI.

C. Recent urinary tract instrumentation or indwelling catheters are the

most common risk factors for nosocomial infections.

D. Uncircumcised males have a 10-fold increased risk for UTI compared

to circumcised males. This is presumably due to increased bacterial
adherence to the mucosal surface of the foreskin and bacterial
colonization under the foreskin.

E. Prematurity is a risk factor for UTI because premature infants are

relatively immunocompromised compared to term infants. Risk increases
with decreasing gestational age and birthweight.

F. Prolonged unexplained jaundice

Neonatal jaundice, especially with an onset after 8 days of life, has been
associated with neonatal UTIs..
**Indirect (unconjugated) hyperbilirubinemia is thought to be secondary
to hemolysis caused by E coli infection.
**Direct (conjugated) hyperbilirubinemia-associated UTI is secondary to
cholestasis, but the mechanism is not known
G. Maternal urinary tract infection during pregnancy and premature
rupture of membranes are potential risk factors for UTI.
These were reported in 2 small case series. The increased incidence
may be because these mothers harbor pathogens transmitted to the
infant during birth.

H. White race is risk factor for urinary tract infection.

Febrile white infants have a higher probability of being diagnosed with

UTI compared to black infants or infants of other ethnic groups. This is
especially the case in female white infants. In 1 study, African American
infants were much less likely to be diagnosed with UTI than white or
Hispanic infants.

V. Clinical presentation

The signs and symptoms of UTI in newborns differ from those of older
children. The familiar symptoms of dysuria, frequency, urgency,
malodorous urine, incontinence, suprapubic pain, and hematuria are
often absent or not recognized.

The clinician must retain a high index of suspicion for the diagnosis of a
UTI in a neonate.

****In full-term infants the most common presentation is

a fever of greater than 38.5°C
poor feeding,
lethargy
loose stool
vomiting
failure of thrive
jaundice
***In contrast, premature infants commonly present with
apnea,bradycardia
hypoxia, lethergy
tachypnea,
fevers with a temperature greater than 39°C.34
feeding intolerance
abdominal distension

VI. Diagnosis

A. Laboratory studies

1. Urine anlysis.

***Positive leukocyte esterase suggests inflammation in the urinary tract;

it has a sensitivity of 84% and specificity of 78%.

***Positive nitrite suggests the presence of gram-negative bacteria and

is 98% specific; sensitivity is only 50% why
Dietary nitrates are converted to nitrites by bacteria, and positive urinary
nitrite test has very high specificity (98 %) in diagnosing UTI.
However, a nitrite test is not a sensitive marker of UTI in children,
particularly infants, who empty their bladders frequently as conversion
from nitrates to nitrites usually requires ~4 h of reaction time.
Furthermore, only Gram-negative bacteria convert nitrates to nitrites;
therefore, negative nitrite test results have little value in ruling out UTI.

*** Detection of bacteria by microscopy adds specificity to other urine

findings.
***Hemocytometer white blood cell (WBC) counts in the urine specimen

may be of value in diagnosing UTI. A recent study stated that a minimum

of 3 to 6 WBCs per high-power field depending on urine concentration is
required for a presumptive diagnosis of UTI. Although no single finding on
urinalysis is diagnostic of UTI, neonates without pyuria or bacteriuria have
a very low likelihood of UTI.

2. Urine culture.

A urine culture is no longer recommended in infants <72 hours of age in

an early-onset sepsis workup and is more appropriately done for late-
onset sepsis workup.
a. Supr apubic aspiration and bladder catheterizations are the only truly
reliable methods to obtain urine cultures in neonates (see Chapters 29 and
30).
Cultures obtained from a suprapubic bladder aspiration that grow >1000
colony-forming units (CFU)/mL are significant.
The optimal definition for UTI from catheter-obtained specimens in
neonates has not been established.
However, >50,000 CFU/mL or 10,000 to 50,000 CFU/mL with pyuria on
the urinalysis are generally accepted definitions.

b. Clean -catch or collection bag specimens often are inaccurate due to

contamination and are only clinically reliable if the culture demonstrates no
growth . Due to high false -positive rates , this type of collection is not
recommended.

c. Rapid culture techniques using reverse transcriptase– polymerase

chain reaction and next-generation sequencing to identify organisms are
available in many facilities.
 **** note :
For urine culture results to be reliable, urine specimens should be
processed as expeditiously as possible. If the specimen is not
processed promptly, then it should be refrigerated to pre- vent the
growth of organisms that can occur in urine at room temperature; for
the same reason, specimens that require transportation to another site
for processing should be transported on ice.

B. Imaging after urinary tract infection

1. Renal ultrasound.

****Because of the high rate of congenital anomalies of the kidney and

urinary tract, all neonates with a documented UTI should undergo renal
ultrasound. The timing of this study remains under debate.
Hydronephrosis or upper urinary tract dilatation is the most common
finding.

2. Voiding cystourethrogram.

***Children younger than 2 months of age and any child with an

abnormal renal ultrasound should also have a voiding cystourethrogram
(VCUG) to look for vesicoureteral reflux, obstructive lesions (eg,
ureterocele, posterior urethral valve), or signs of neurogenic bladder.

****VCUG for children older than 2 months of age with normal renal
ultrasound after first febrile UTI is controversial and is currently not
recommended by the American Academy of Pediatrics (AAP).

*** Any child with a history of >1 febrile UTI should undergo a VCUG.
If a decision is made to perform a VCUG, one should consider
performing it 2 to 4 weeks after the infection to ensure that the infection
is appropriately treated before instrumentation.
3. Watchful waiting without voiding cystourethrogram.

***In children 0 to 3months of age with E coli UTI (first, febrile UTI) and
normal renal ultrasound, watchful waiting without VCUG can be
considered. This is based on evidence that the probability of high-grade
vesicoureteral reflux was low in children with E coli UTIs and normal
renal ultrasounds (1%).

***The presence of non–E coli UTI increased the probability of high-grade

vesicoureteral reflux to 26%, and adding an abnormal renal ultrasound
further increased the probability to 55%.

4. Other imaging studies. Ultrasound of the spine or magnetic resonance

imaging (MRI) of the spine may be considered if there is evidence of
neurogenic bladder.

***MRI of the urinary tract is rarely done but can provide excellent
anatomic detail of the urinary tract. Diuretic renogram can be done to
localize and quantify the degree of urinary tract obstruction.

5- 99Tc-Dimercaptosuccinic Acid Renal Scan

***DMSA scan is the current gold standard for assessment of renal

parenchymal injury in children with a history of febrile UTI.

It is more sensitive for renal scarring than RBUS, which misses a

substantial proportion of such cases.

**If a DMSA scan is to be performed, a delayed one at 4 to 6 months

after UTI resolution allows the acute inflammatory reaction to subside, at
which point any persistent cortical defects can be assumed to represent
permanent renal scarring.

***DMSA cannot replace VCUG in the detection of VUR or high-grade

VUR.
v prophylaxis :

antibiotic prophylaxis

**** The AAP Red Book states that “data do not support the use of
antimicrobial prophylaxis to prevent febrile recurrent UTIs in infants
without vesicoureteral reflux.” For neonates with vesicoureteral reflux,
moderate to severe hydronephrosis, or other abnormalities such as
posterior urethral valves,If vesicoureteral reflux is present,
prophylaxis is continued

***antibiotic prophylaxis should be considered. Amoxicillin (10 mg/kg/d) is

the most commonly used.. Trimethoprim- sulfamethoxazole is
contraindicated because of liver and kidney immaturity in neonates.

***Until age 2 months, the infants receive cephalexin to be replaced then

by sulfamethoxazole/trimethoprim. Due to the high rate of resistance of
community E. coli to ampicillin, which in some places reaches 50 %, it is
important to avoid using this drug as first-line

Circumcision

***should be considered in uncircumcised males with a history of

recurrent UTIs. Newborn circumcision is a common procedure with
relatively few associated complications. Pathogenic bacteria may be
more adherent to the mucosal surface of the foreskin than the keratinzed
surface of the penis after circumcision. In theory, circumcision also
reduces the bacterial colonization of the periurethral area, thereby
reducing the risk of UTIs. The AAP feels that the potential benefits of
male circumcision outweigh the risks; therefore, the procedure should be
accessible to families who choose it.
***There is insufficient evidence to recommend routine circumcision in
all newborns. The risks and potential benefits of the procedure should
be outlined to parents to help them make an informed decision.

*** Circumcision should be avoided in cases of hypospadias,

ambiguous genitalia, and bleeding disorders .

VII. Management

Initial antibiotic treatment.

*** For the majority of neonatal cases, initial treatment with broad-
spectrum intravenous (IV) antibiotics is appropriate (usually ampicillin
and gentamicin).

It is also important to consider maternal use of antibiotics prior to

delivery (which increases the risk of a neonatal UTI with β-lactamase–
producing E coli) and local antibiotic resistance patterns. Antibiotics can
be tailored according to susceptibility testing on urine culture. Ideal
duration of therapy is not completely known but is usually 10 to 14 days.

*** For an infant in the hospital who is older than 7 days, consider
vancomycin and gentamicin. to cover the possibility of hospital-acquired
organisms until definitive culture results are available.

***Oral antibiotics can be initiated for mature infants who are able to
tolerate oral intake and who are not ill appearing. A delay in initiation of
antibiotic treatment of 72 hours or more was a risk factor for permanent
renal scars after the first febrile UTI.

***There is no difference in renal scarring between oral and IV antibiotic

therapy.