UTI

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URINARY TRACT INFECTION

• Invasion of urinary tract by pathogens - upper or


lower tract.

• Common cause of morbidity.

• Long-term complications - hypertension and chronic


renal failure.

• Prompt detection and treatment of UTI and


complicating factors are of utmost importance.
EPIDEMIOLOGY
• Third most common bacterial infection in children in
developing countries after those of the gastrointestinal and
respiratory tract.
• Term neonates – 1%
• Preterm Neonates – 3%
• Male : Female in neonates – 5:1
• Male : Female in infants – 1:1
• Males < 14 years – 1-2 %
• Females < 14 years – 3-8 %
DEFINITIONS
TERM DEFINITION
Significant bacteriuria Colony count of >1,00,000/mL of a single species
in a midstream clean catch sample.

Asymptomatic bacteriuria Significant bacteriuria in the absence of


symptoms of urinary tract infection (UTI).

Simple UTI UTI with low grade fever, dysuria, frequency, and
urgency; and absence of symptoms of
complicated UTI.

Complicated UTI Presence of fever >39ºC, systemic toxicity,


persistent vomiting, dehydration, renal angle
tenderness and raised creatinine.

Recurrent UTI Second episode of UTI.


ETIOLOGY
• E.coli – 90 % of first symptomatic UTI and 70%
of recurrent UTI.
• Proteus, Pseudomonas - recurrent UTI,
obstruction, instrumentation and nosocomial
infections.
• Fungal – Preterms (C.albicans),
immunocompromised.
PERIURETHRAL BACTERIAL FLORA
• Healthy girls - lactobacilli and other commensals.

• Lactobacilli – prevent epithelial attachment by virulent organisms.

• Recurrent UTI – colonization with uropathogens.

• Infants and toddlers – fecal organisms of low virulence - E. coli and


enterococci.

• Broad spectrum antibiotics (amoxycillin) - eliminate protective flora


and predispose to UTI.
PATHOGENESIS
• Neonates – Hematogenous spread (Acute bact pyelonephritis
<-> Septicemia).

• Other ages – Through ascending route into bladder, through


VUR into ureters and kidneys.

• Boys – bacteria under prepuce – circumcision.


PREDISPOSING FACTORS
• Female gender
• Uncircumcised infants (10 times risk)
• White race
• Obstructive uropathy
• Stones in the urinary tract
• Incomplete emptying of bladder with residual urine
• Constipation
• Born to mother with bacteriuria during pregnancy
• Broad spectrum antibiotics
HOST DEFENCE
• Normal voiding – insignificant
• Bladder epithelial cells
• Secretory IgA in urine
• Blood group antigens (impede adhesion)
• Human breast milk – anti adhesive factors,
stabilises intestinal flora with less pathogenic
organisms
CLINICAL FEATURES
Neonates –
• Part of septicemia
• Unexplained fever, vomiting, lethargy, jaundice, seizures,
shock, failure to thrive

Infants & Young Children –


• Strong suspect – unexplained fever in children < 2 years of age
• Recurrent fever, diarrhoea, vomiting, abdominal pain, poor
weight gain
Older Children –
• Distal urinary tract - Dribbling, prolonged voiding, straining, crying
during micturition and poor urinary stream.

• Voiding dysfunction - Diurnal incontinence, urgency, frequency and


squatting.

• Cystitis - Dysuria, frequent voiding and hypogastric pain.

• Parenchymal involvement - Fever, chills and rigors and flank pain.

• Urinary stasis (mechanical or neurogenic) having UTI from urea-


splitting organisms - Proteus and Klebsiella - hyperammonemia
and encephalopathy.
• Examine for degree of toxicity, dehydration and ability to
retain oral intake.
• Record blood pressure.
• History regarding bowel and bladder habits have to be
elicited.
• Child is examined for features that suggest an underlying
functional or urological abnormality
BOWEL BLADDER DYSFUNCTION

• Recurrent UTI or persistent VUR - associated voiding


disorder
• Abnormal patterns of micturition in presence of intact
neuronal pathways without congenital or anatomical
abnormalities.
• Abnormal bladder pressure and urinary stasis -
recurrent UTI.
• Abnormality either during the i) filling phase as in an
overactive bladder, or ii) evacuation phase as in
dysfunctional voiding.
• Since constipation is often associated with a functional
voiding disorder, the condition is referred to as Bowel
bladder dysfunction (BBD).
DIAGNOSIS

• URINE MICROSCOPY
• RAPID DIPSTICK TESTS
• URINE CULTURE
COLLECTION OF URINE SPECIMEN

• SUPRAPUBIC ASPIRATION – Neonates, infants and young


children
• CATHETERISATION – Neonates, infants and young children
• MID-STREAM CLEAN CATCH SAMPLE – Older children
SUPRAPUBIC ASPIRATION
• A clean-catch midstream specimen - minimize
contamination by periurethral flora.
• Washing the genitalia with soap and water.
• Antiseptic washes and forced retraction of the
prepuce are not advised.
• Cultures of specimens from urine bags - high false
positive rates.
• Plated within one hour of collection.
• If delay is anticipated, the sample can be stored in a
refrigerator at 4ºC for up to 12-24 hours.
URINE MICROSCOPY
• Provisional diagnosis of UTI if it shows bacteria and
neutrophils.
• Significant pyuria –
>10 leukocytes per mm3 in a fresh uncentrifuged sample
>5 leukocytes per high power field in a centrifuged sample
• Leukocyturia is occasionally absent in infants with UTI.
• Leukocyturia may be seen in healthy girls due to vaginal
contamination.
• Leukocytes may lyse rapidly in dilute or alkaline urine or if
urine microscopy is delayed.
URINE DIPSTICK
• Urinary bacteria convert nitrate to nitrite
• The intensity of color change is proportional to the number of
bacteria in the urine

• Production of esterase by neutrophils in the urine can be


detected by chemical methods.
• Sensitivity of these tests is lower in children below 2 years of
age
NITRITES DIPSTICK

• Although nitrates are excreted by the kidney, nitrites are not


normally found in urine
• More than 10,000 bacteria per ml to turn the dipstick positive
• Specific but not a very sensitive test
• All the Enterobacteriaceae and most of the non-fermenters
• Candida and Streptococci including Enterococci do not reduce
nitrates.
URINE CULTURE
• Confirmed by isolation of significant number of bacteria on urine
culture.
• Repeated in case contamination is suspected
i) mixed growth of two or more pathogens
ii) growth of organisms that normally constitute the periurethral flora
(lactobacilli in healthy girls; enterococci in infants and toddlers)
iii) When UTI is strongly suspected but colony counts are equivocal.
METHOD OF COLONY COUNT PROBABILITY OF
COLLECTION INFECTION
Suprapubic Any number of 99%
aspiration pathogens
Urethral >50,000 CFU/mL 95%
catheterization
Midstream clean >1,00,000 CFU/mL 90-95%
catch
OTHER INVESTIGATIONS

• Neonates and infants – Blood culture


• CBP – Neutrophilic leukocytosis
• Raised ESR and CRP
• Blood urea and serum creatinine
IMMEDIATE TREATMENT

• Need for hospitalization - patient’s age, features suggesting


toxicity and dehydration, ability to retain oral intake and
likelihood of compliance with medication(s).
• Less than 3 months of age or complicated UTI - hospitalized
and treated with parenteral antibiotics.
• Simple UTI and above 3 months of age - oral antibiotics.
• Choice of antibiotic should be guided by local sensitivity
patterns.
• A third generation cephalosporin is preferred.
• Therapy with a single daily dose of an aminoglycoside may be
used in children with normal renal function.
• Once the result of antimicrobial sensitivity is
available, the treatment may be modified.

• With adequate therapy, there is resolution of fever


and reduction of symptoms by 48-72 hours.
DURATION OF THERAPY

• Infants and children with complicated UTI – 10-14 days.

• Children with uncomplicated UTI – 7-10 days.

• Adolescents with cystitis - 3 days.

• Following the treatment of the UTI, prophylactic antibiotic


therapy is initiated in children below 1 year of age, until
appropriate imaging of the urinary tract is completed.
SUPPORTIVE THERAPY

• Adequate hydration.

• Routine alkalization of the urine is not necessary.

• Paracetamol for fever; therapy with non steroidal anti-


inflammatory agents should be avoided.

• A repeat urine culture is not necessary, unless there is


persistence of fever and toxicity despite 72 hours of adequate
antibiotic therapy.
EVALUATION AFTER THE FIRST UTI

• To identify patients at high risk of renal damage, chiefly those


below one year of age, and those with VUR or urinary tract
obstruction.
• Ultrasonogram - kidney size, number and location,
presence of hydronephrosis, urinary bladder
anomalies and post-void residual urine.

• DMSA scintigraphy - detect renal parenchymal


infection and cortical scarring.

• MCU - VUR and provides anatomical details


regarding the bladder and the urethra.
INVESTIGATION WHEN TO DO?

USG KUB As soon as diagnosed as UTI

MCUG 2-3 weeks after treatment

DMSA 2-3 months after treatment

• Hydronephrosis in the absence of VUR – evaluate by


diuretic renography using 99mTc-labeled
diethylenetriamine pentaacetic acid (DTPA) or
mercaptoacetylglycine (MAG-3) - provide
quantitative assessment of renal function and
drainage of the dilated collecting system.
PREVENTION OF RECURRENT UTI

General -
• Adequate fluid intake and frequent voiding
• Constipation should be avoided
• In children with VUR who are toilet trained, regular
and volitional low pressure voiding with complete
bladder emptying is encouraged
• Double voiding ensures emptying of the bladder of
post void residual urine
• Circumcision in infant boys
ANTIBIOTIC PROPHYLAXIS

• Long-term, low dose, antibacterial prophylaxis is


used to prevent recurrent, febrile UTI.
Indications -
• Depend on patient age and presence or absence of
VUR.
(i) UTI below 1-yr of age, while awaiting imaging
studies,
(ii) Vesico-ureteric reflux,
(iii) frequent febrile UTI (3 or more episodes in a
year) even if the urinary tract is normal.

• Not advised in patients with urinary tract obstruction


(e.g., posterior urethral valves), urolithiasis and
neurogenic bladder, and in patients on clean
intermittent catheterization.
Breakthrough UTI on Prophylactic Antibiotics
• Results either from poor compliance or associated
voiding dysfunction.
• Should be treated with appropriate antibiotics.
• Change of the medication being used for prophylaxis
is usually not necessary.
ASYMPTOMATIC BACTERIURIA

• Presence of significant bacteriuria in the absence of


symptoms of UTI.
• 1-2% in girls and 0.2% in boys.
• Benign condition – no renal injury.
• Most common organism - E. coli (less virulent strains).
• Eradication of these organisms - symptomatic infection with
more virulent strains.
• Therapy of asymptomatic bacteriuria or antibiotic prophylaxis
is not required.
• Presence of asymptomatic bacteriuria in a patient previously
treated for UTI should not be considered as recurrent UTI.
INDICATION FOR REFERRAL TO A PEDIATRIC
NEPHROLOGIST
• Recurrent urinary tract infections
• Urinary tract infections in association with bowel
bladder dysfunction
• Patients with vesicoureteric reflux
• Underlying urologic or renal abnormalities
• Children with renal scar, deranged renal functions,
hypertension
VESICO-URETERIC REFLEX
• Retrograde passage of urine into the upper urinary tract
during detrusor contraction at micturition.
• Primary VUR is an autosomal dominant condition.

• Incidence in siblings is 30-35 %.

• In association with other congenital abnormalities


such as megacystis-megaureter, duplex systems,
posterior urethral valve and ectopic ureters.

• VUR can also appear as an acquired defect in a large


proportion of patients with neuropathic bladder
(secondary VUR).
• Incidence in term or pre-term neonates is 0.4
percent.
• 30-40 percent of children and 40-50 percent of
neonates with UTI have VUR.
• Up to 20 to 40 percent of children with UTI and VUR
develop renal scarring, of which 5 to 10 percent
progress to end stage renal disease.
• Gross VUR during infancy is mostly seen in boys and
is usually bilateral.
• In older children, girls are more often affected and
have milder VUR.
GRADE – I Reflux into the non-dilated distal ureter but does not reach kidney

GRADE – II Reflux up to kidney in non-dilated ureter

GRADE – III Reflux into dilated ureter with mild-moderate dilation of renal pelvis

GRADE – IV Reflux into grossly dilated ureter and renal pelvis and calyces are dilated

GRADE - V Massive reflux with ureteral dilation and tortuosity and effacement of
calyceal details.
MANAGEMENT
• The main objective of treatment is to prevent
development of reflux nephropathy.
• UTI must be recognized promptly, confirmed by
culture and treated aggressively.
• Regular timed voiding, every 4-5 hours, is very
helpful.
• Long-term prophylaxis with antibiotics is the
mainstay in the management of children with VUR.
VUR GRADE MANAGEMENT
Grades I and Antibiotic prophylaxis until 1 yr old.
II Restart antibiotic prophylaxis if
breakthrough febrile UTI.
Grades III to Antibiotic prophylaxis up to 5 yr of age.
V Consider surgery if breakthrough febrile
UTI. Beyond 5 yr: Prophylaxis continued
if there is bowel bladder dysfunction.
• A close follow up is required for occurrence of
breakthrough UTI.

• Repeat imaging - After 18-36 months in patients


with grade III-V VUR.

• Radionuclide cystogram - preferred for follow-up


evaluation (lower radiation exposure, has higher
sensitivity for detecting reflux).
INDICATIONS FOR SURGICAL REPAIR

• Surgical repair is done in Grade III-V VUR if


i) they have breakthrough febrile UTI
ii) parents prefer surgical intervention to prophylaxis
iii) in patients who show deterioration of renal
function
• An evaluation for voiding dysfunction (based on
history, voiding diary) should be done before surgery.
• Antibiotic prophylaxis is continued for 6 months after
surgical repair.
ENDOSCOPIC REPAIR

• Dextranomer/hyaluronic acid copolymer (Deflux) endoscopic


treatment - an alternative to surgical repair for VUR.

• Patients with bowel bladder dysfunction may show


persistence and/or recurrence of reflux and progressive renal
damage.

• Endoscopic correction is currently not recommended as first


line therapy
LONG TERM FOLLOW-UP

• Patients with a renal scar (reflux nephropathy) are


counseled regarding the need for early diagnosis and
therapy of UTI and regular follow up.
• Physical growth and blood pressure should be
monitored every 6-12 months, through adolescence.
• Investigations include urinalysis for proteinuria and
estimation of blood levels of creatinine.
• Annual ultrasound examinations are done to
monitor renal growth.
REFERENCES

• Bagga’s Texbook of Pediatric Nephrology


• Revised Statement on Management of UTI – Indian society of
Pediatric Nephrology
• Urinary Tract Infections - Rachel Millner, MDa, Brian Becknell,
MD, PhDb,c,d
• Nelson’s Pediatrics South Asian Edition

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