Uti in children

Introduction

Pediatric UTIs often signal an underlying genitourinary tract abnormality

Can lead to renal scarring with resultant hypertension and renal failure

Difficult to diagnose because symptoms are non-specific in this age group and testing is often invasive

Pediatric UTIs: Epidemiology

Prevalence Girls—6.5-8% Boys—2-3%

Uncircumcised boys have a 5-20 X increase in UTIs vs circumcised boys

Occurs in about 7% of children <2 who present with fever without a source

Epidemiology (continued)

Incidence of vesicoureteral reflux (VUR) is 1% in children < 2 yoa. 50% of kids <1 yoa with UTI have VUR

Early renal scarring is nearly twice as common in this age group.

Incidence of scarring increases with each subsequent UTI Scarring occurs in 5-38% of febrile UTI’s.

Figure 1Prevalence of VUR by age. Plotted are the prevalencesreported in 54 studies of urinary tract infections inchildren (references in Technical Report).

Pediatrics 1999; 103: 843-852

Figure 2Relationship between renal scarring and number ofurinary tract infections.16

Pediatrics 1999; 103: 843-852

UTI: Classiffication

Classification: Upper tract infection

Acute pyelonephritis- fever, bacteriuria, systemic symptoms

Lower tract infection Urethritis Cystitis Voiding symptoms, little or no fever, no

systemic symptoms

Clinical Presentation

Age and gender dependent 0 - 2 months:

Fever 2 mo.– 2 y/o:

Fever (>38 C) Irritability Vomiting and Diarrhea Decrease appetite Between 1-2 y/o = crying on urination, foul

smelling odor

Clinical Presentation

2 y/o – 6 y/o: Systemic symptoms Fever Flank or back pain Urgency, urinary incontinence, dysuria Suprapubic or abdominal pain Foul smelling odor

> 6 y/o and adolescents: Same as above

Urethritis

In female infants Part of a diaper

dermatitis In adolescent girls

and boys Presenting sign of

STD

In pre-school and school age girls Part of “non-specific”

vulvovaginitis Generally environmental Bubble bath Nylon panties (also biker

shorts, leotards, bathing suits)

Poor hygiene (not wiping, wiping back to front)

Overzealous hygiene Use of baby powder,

perfumes

Symptoms of urethritis

Dysuria Reluctance to void Perineal discomfort, erythema May be associated with vaginal

irritation and erythema in girls In older boys, urethral discharge In adolescent girls associated with

PID symptoms

Cystitis

Afebrile usually Frequency Enuresis Dysuria Reluctance to void

Pyelonephritis

Usually associated with fever and systemic signs 2° renal parenchymal inflammation

Older children Flank pain or abdominal pain

Younger children Fever, irritability, vomiting, poor

feeding

Pyelonephritis - Significance

EACH infection results in scar formation and reduced renal function

After diabetes mellitus and collagen vascular disease, undetected renal disease and untreated childhood UTI may be responsible for: A large of portion of ESRD in adults A huge need for dialysis and transplantation

Pyelonephritis - Significance

Untreated childhood UTI responsible for: Hypertension Impaired kidney function Complications of pregnancy

Causes and course of UTIGut flora Bacterial virulence

Uropathogenic strain Colonisation of the urethra and the perineum (in females the vagina)

Mucosa barriere

Host Increased adherence immunstatus

VUR obstruction foreign body previous inflammations

cystitis

akute pyelonephritis

healed urosepsis scar

hypertension CRF...

Risk Factors

Age <1 year Female gender Uncircumcised

males Constipation Voiding

dysfunction

Improper wiping Genitourinary

abnormalities Vesicoureteral

reflux Obstruction

Colonization with virulent E. Coli

Signs and Symptoms – Children 2 months to 2 years

Fever—usually unexplained Vomiting and/or diarrhea Abdominal Pain Failure to thrive Malodorous urine Crying on urination

Signs and Symptoms – Children >2

Fever Vomiting and/or diarrhea Abdominal pain Malodorous urine Frequency and/or urgency Dysuria New incontinence

Summary

Urinary tract infections are a common cause of fever without a source in children <2 and can lead to renal scarring, HTN or ESRD. Rapid treatment is essential.

Symptoms are non-specific and thus a high level of suspicion is required

Urine culture is required for diagnosis, and should be obtained by catheterization or SPA when child is ill or infection is suspected

Treatment requires a 7-14d course of antibiotics Prophylactic abx are required after initial

treatment All Children <2 require 2 imaging studies after

initial UTI

References

Committee on Quality Improvement, Subcommittee on Urinary Tract Infection. The diagnosis, treatment, and evaluation of the initial urinary tract infection in febrile infants and young children. Pediatrics 1999; 103:843-852

Layton, KL. Diagnosis and Management of Pediatric Urinary Tract Infections. Clinics in Family Practice 2003; 5: 2

Chon DH, Frank CL, Shortliffe LM. Pediatric Urinary Tract Infections. Pediatric Clinics of North America 2001; 48: 1441-1459

Linderd KA, Shortliffe LM. Evaluation and management of pediatric urinary tract infections. Urologic Clinics of North America 1999; 26: 719-728

McCollough M, Sharieff G. Marx: Rosen’s Emergency Medicine: Concepts and Clinical Practice, 5th ed.2002; 2327-2334

Acute Urinary Tract Infections Clinical Effective Committee. Evidence based clinical practice guideline for patients 6 years of age or less with a first time acute urinary tract infection. Cincinnati (OH): Children’s Hospital Medical Center 1999; 1-14

Patient groups Infants of 1 year Girls and boys Recurrent UTI (no abnormalities) Mild VUR (grade I and II)

Options Long-term low dose antibiotics (Cochrane review)

(Trimethoprim, Nitrofurantoin, Cotrimoxazole) Intermittent treatment of UTIs

Time horizon 3 years of long-term antibiotics and follow-up to end

stage renal disease

NHS perspective

long-term antibiotic treatment for preventing recurrent urinary tract infections (UTI) in children

Model Structure for UTI

No UTI

1 UTI

2 UTIs

3 UTIs

4 UTIs

Age atESRD onset

Frequency of recurrent UTIs

Number of pyelonephritic attacks

Progressive renal scaring

End-stage renal disease

TransplantPyelonephritic

attack

Pyelonephritic attack

Pyelonephritic attack

Pyelonephritic attack

Number of attacks

Progressive renal

scaringDevelopment

of ESRD

Dialysis

No UTI

1 UTI

2 UTIs

3 UTIs

4 UTIs

Age atESRD onset

Frequency of recurrent UTIs

Number of pyelonephritic attacks

Progressive renal scaring

End-stage renal disease

TransplantPyelonephritic

attack

Pyelonephritic attack

Pyelonephritic attack

Pyelonephritic attack

Number of attacks

Progressive renal

scaringDevelopment

of ESRD

Dialysis

The evidence

Effectiveness• Existing reviews (variable quality)• Meta analysis, Multiple parameter synthesis• Probabilistic trial based model

Natural history• Epidemiological studies• Pooled trial baselines• Registry studies• Clinical judgement

Quality of life • Published studies• Survey

Costs • Published studies• Published unit costs and dosage (BNF, PSSRU, CIPFA)

Antenatal Period

The most common cause is physiologic dilation.

Metanephric urine production begins at 8 weeks, even before ureteral canalization is complete.

Transient obstruction with hydronephrosis occurs.

Embryology

Pathophysiology:

Anatomic and functional processes interrupts the flow of urine.

There is a rise in ureteral pressure causing stretching and dilation; if pressures continue to rise, leads to decline in renal blood flow and GFR.

When significant obstruction is persistent, it affects nephrogenic tissue and results in varying degrees of cystic dysplasia and renal impairment.

Grading of Severity of Hydronephrosis

Grade Central RenalComplex

RenalParenchymalThickness

0 Intact Normal

1 Slight splitting Normal

2 Evident splitting Normal

3 Wide splitting Normal

4 Further dilatation Thin

Most Common Causes in Neonates:

Ureteropelvic Junction Obstruction Ureterovesical Junction Obstruction Posterior Urethral Valves Eagle-Barrett Syndrome (a.k.a.

Prune Belly Syndrome) Vesicoureteral Reflux Ureterocele

Treatment for UPJ: Pyeloplasty

Diagnosis

Urine Collection

Clean Catch acceptable for toilet trained children (wearing underwear or pull-ups) Ensure cleansing with antiseptic

towelette Catheterized specimen in diapered

children Suprapubic bladder tap in <6 month

old child is guaranteed sterile

Leukocyte Esterase

Has to accumulate in urine Insufficient accumulation possible in

small infants who void frequently Infants <3 months old may not have

mature enough immune system to induce leukocytes in urine (beware neutropenia on CBC)

Nitrites

By-products of E. coli and other lactose fermenters (glucose digestion)

Insufficient accumulation possible in small infants who void frequently

Insufficient accumulation possible in older child during the day and in older patient who has significant frequency

If positive, highly suggestive of UTI (high specificity)

Microscopy

>10 WBC/hpf on spun urine Bacteria on unspun urine are

common unless catheterized specimen

Gram stain is very helpful on spun urine

Standard UA plus gram stain is “enhanced UA”

Urine Culture

>100,000 cfu per mL on any culture >10,000 cfu per mL on cath

specimen ANY bacterial growth on bladder tap

(at least 1,000 cfu/mL)

Sensitivity and Specificity of Components of the UA

TestSensitivity %

(Range)Specificity %

(Range)

Leukocyte esterase

Nitrite

Leukocyte esterase or nitrite positive

Microscopy: white blood cells

Microscopy: bacteria

Leukocyte esterase or nitrite orMicroscopy positive

83 (67.94)

53 (15-82)

93 (90-100)

73 (32-100)

81 (16-99)

99.8 (99.100)

78 (64-92)

98 (90-100)

72 (58-91)

81 (45-98)

83 (11-100)

70 (60-92)

Urine Cultures

Held for 48 h but usually positive at 24 h for true UTI

Requires another day for ID of organism

May require another day for sensitivities

If contains skin flora (S. epi., S. aureus or α-strep.) considered contamination secondary to poor specimen collection

Diagnosis

Urinalysis Can be obtained by most convenient

means if infant is not ill UTI CANNOT be diagnosed with UA

alone If suspicious UA, the Urine Culture must

be obtained via SPA or catheter specimen

If UA does not suggest UTI, it is reasonable to follow child clinically

Table 1. Sensitivity and Specificity of Components of the Urinalysis, Alone and in Combination (References in Text)

Test Sensitivity %(Range)

Specificity %(Range)

Leukocyte esterase 83 (67-94) 78 (64-92)

Nitrite 53 (15-82) 98 (90-100)

Leukocyte esterase or nitrite  positive

93 (90-100) 72 (58-91)

Microscopy: WBCs 73 (32-100) 81 (45-98)

Microscopy: bacteria 81 (16-99) 83 (11-100)

Leukocyte esterase or nitrite or  microscopy positive

99.8 (99-100) 70 (60-92)

Pediatrics 1999; 103: 843-852

Diagnosis

Urine Culture MUST be collected via catheter or SPA UTI CANNOT be diagnosed from a bag

specimen Diagnosis of UTI requires Urine Culture

LOE--Strong

Urine Collection: Suprapubic Aspirate

“Gold standard” - >99% specificity Positive culture: any number of g-

bacilli or >3000 CFU of g+ cocci

Urine Collection: Transuretheral Catherization

>105 CFU - 95% specificity 104 – 105 CFU – infection is likely 103 – 104 CFU – Suspicious <103 CFU – infection unlikely

treatment

Treatment

May initiate treatment either orally or parenterally

Admit and use parenteral antibiotics if toxic, dehydrated or unable to take PO

Choices: TMP/SMX Cephalosporin Amoxicillin (check local resistance)

Treatment--continued

Improvement should be seen in 24-48 hours

If not having expected clinical response in 2 days, re-culture, consider changing antibiotics and do imaging studies

Complete 7-14 day course of antibiotics 14 days should be given for those that were

ill with clinical evidence of pyelonephritis

Prophylaxis

After completion of initial antibiotics, children should be give a prophylactic dose of antibiotics until imaging studies complete

Antibiotic should have high urinary excretion and low serum and fecal levels, thus minimizing the development of resistance.

Imaging

Needs to be performed in ALL children <2 years old with initial UTI

Need to perform at least 2 studies to image the upper and lower urinary tracts

Acute imaging only necessary when appropriate clinical response is not achieved within 2 days

Ultrasound

Should be done on all infants < 2yoa after their initial UTI

Helps to detect hydronephrosis and ureteral dilation

Has replaced IVP Need additional study to evalute VUR Is not as sensitive as renal cortical

scintigraphy (DMSA) for detecting inflamation and scarring

Voiding Cystourethrography (VCUG)

Used to identify and grade reflux Also evaluates the urethra and bladder for

abnormalities – important for boys who may have posterior urethral valves and girls with voiding dysfunction

Radionuclide cystography (RNC) – can also evaluate reflux, but does not delineate the lower tract anatomy well. Can be used for follow-up exams as has low ratiation dose

Renal Cortical Scintigraphy (DMSA)

Very sensitive for evaluating acute inflammation from pyelonephritis as well as renal scarring

Role in clinical management is still unclear

Treatment

No “short course” therapy for small children

No “short course” therapy for males Empiric therapy is directed at

organisms and adjusted for age. Choose narrowest spectrum

allowable considering host factors Adjust therapy when sensitivities

available

IV antibiotics-Indications

Any person of any age who appears clinically toxic or who has neutropenia

Infants <1 mo until bacteremia, sepsis, & meningitis ruled out

Children unable to tolerate oral antibiotics

Immunocompromised patients

Antibiotic choice

Neonates Ampicillin plus a second antibiotic (usually

gentamycin or cefotaxime) to cover for GBS, Listeria, as well as gram negative organisms

S. aureus and S. epi. can cause hematogenous pyelonephritis (in children instrumented :ET tube,central lines, etc)

Vancomycin may be indicated for toxic patients or those unresponsive to initial therapy

Therapy

Cefixime (Suprax) oral is as effective as parenteral ceftriaxone

Cefpodoxime (Vantin) Bad tasting 10 mg/kg/day

Fluoroquinolones are expensive and ”off label” in pedi

Bacterial virulence Bacterial spectrum at the Ist Dept. of Pediatrics, in 2002-2003

N=7850 (%) E. coli 49 Enterococcus faecalis 13 Proteus indol neg. 10 Klebsiella 7 Pseudomonas spp 7 Enterobacter spp 6 Proteus indol pos 3 Staphylococcus 3 Other 2

Sensitive host

Age related factorsAnatomy (short urethra, phymosis and

adhesio cellularis preputii et labia minora, diaper)

colonization Immunological susceptibility

Mucosal barrier Inherited/acquired

immunresponse Inherited/acquired

Ex: IgA deficiency, P1 blood group

Sensitive host

Anatomical malformationsobstructionVURmeningomyelokeleprune-belly syndromeStone disease, etc

Age-related incidence of UTI

0 10 20 30 40 50 60 70 80

age (years)

rela

tive

risk

boys girls

neonate child > 3(6)y systemic infection cystitis hospitalize outpatient i.v. antibiotics (AB) per os AB

US

Adjust treatment according to bacteriology

(in case of relaps)

MCU US 4-6 weeks after the acute phase norm: care for 1 y pathological: scintigraphy (ivu) prophylaxis+surg.

Management of UTI

Prognosis

UTI Controversy #1:Antibiotic Prophylaxis

Indications grade 1 VUR frequent UTI recurrences

Problems Pt Rxd with antibiotic prophylaxis

Increased infection with Proteus and Enterobacter pseudomonas and Candida increased in children

with urogenital abnormalities Drug toxicity and sensitivities

Antimicrobial choices (qhs better) TMP-SMX or Nitrofurantoin (GI disturbance) Keflex if < 3 months Quinolones in some circumstances

Posterior Urethral Valves

Abnormal congenital mucosal folds that are thin membranes impeding bladder drainage.

Most common obstructive urethral lesion in male newborns found at the distal prostatic urethra.

Incidence is approx’ly 1 in 8,000 males. Approx’ly 50% have reflux. VCUG is the modality of choice.

Radiographic signs of PUV:

distended prostatic urethra

valve leaflets bladder and/or

bladder neck hypertrophy

diverticula narrow stream in the

penile urethra incomplete emptying

of the bladder

Treatment of PUV:

Transurethral valve ablation, vesicostomy or upper tract diversion

Urethral stricture is a common complication

Fetal intervention carries a high risk with mortality rate of 43%

ESRD, renal insufficiency and chronic renal failure are long-term consequences

30% of boys with posterior urethral valves whose symptoms present in infancy are at risk for progressive renal insufficiency.

PUV, 2 months , MCU

PUV, 2months

Mcu done for suspected PUV

9 months old child with dribbling of urine and difficulty in passing urine

?PUV MCU done Uroprophylaxis suggested Told by another Doc: not necessary Came with high grade fever after 1 month UTI

Vesicoureteral Reflux Retrograde propulsion of urine into the upper

urinary tract during bladder contraction. Primary reflux is caused by attenuation of

the trigone and the contiguous intravesical ureteral musculature.

May be caused by the ectopic insertion of the ureter into the bladder wall resulting in a shorter intravesicular ureter, which acts as an incompetent valve during urination.

The ratio of the submucosal tunnel length to the ureteral diameter is the primary factor determining the effectiveness of the normal valve mechanism.

It is normally 5:1, and in those with reflux it is 1.4:1.

The intramural length increases from 0.5 cm at birth to 1.3 cm by 12 years of age.

Duplication of the collecting system and ureteroceles should also be considered.

Some clinical facts about VUR:

It is genetic. Occurs in about 30% of first-degree

relatives. 1/3 of children with a urinary tract

infection has reflux on VCUG. Primary reflux tends to resolve over

time as intravesical segment elongates with growth.

Grading of Vesicoureteral Reflux

VUR Grading

Grade I Grade II Grade III

Grade IV Grade V

Prognosis - 5% adultsScarring - 5-50%ScreeningUTI

Prognosis: Resolves

spontaneously before adolescence in: 90% of Gr. 1 reflux 80% of Gr. 2 50% of Gr. 3 10% of Gr. 4 0 in Grade 5 reflux

Kidney is most susceptible to scarring in the first year of life and at the time of first upper tract infection.

Scars less frequently develop after the age of 5.

VUR and scarring lead to hypertension, progressive renal insufficiency and failure.

Treatment:

Observation Medical treatment of infections Surgical treatment

significant hydroureteronephrosis indicated if impossible to keep urine

sterile and reflux persists acute pyelonephritis occurs evidence of increasing renal damage

VUR

MCU

C/o Recurrent UTI

Management of VUR I-III (IV)-V conservative operative UTI neurogenic bladder scar duplex system non-compl. Solitary kidney transplanted kidney

? pontaneous resolution STING / SMING neoimplantation

Endoscopic submucosal injection

Endoscopic submucosal injection

• Teflon• Silicon• Collagen

Bacterial virulence Virulence=factors that enable bacteria to

invade the urinary tract Surface antigenes

O: lipopolysacharides with endotoxin properties. Induces fever, local inflammation

K, (capsular) antigene, prevents phagocytosis

“P” fimbriae: bind to glycolipid receptors of the P blood group family

A number of further factors not routinely checked

Bacterial virulence

Pyelonephritis: 3-4 (known) virulence factors

Cystitis: 0-2 factors

CAVE: OBSTURCTION !! MALFORMATION !!