2IntroductionPediatric UTIs often signal an underlying genitourinary tract abnormalityCan lead to renal scarring with resultant hypertension and renal failureDifficult to diagnose because symptoms are non-specific in this age group and testing is often invasive
3Pediatric UTIs: Epidemiology PrevalenceGirls—6.5-8%Boys—2-3%Uncircumcised boys have a 5-20 X increase in UTIs vs circumcised boysOccurs in about 7% of children <2 who present with fever without a source
4Epidemiology (continued) Incidence of vesicoureteral reflux (VUR) is 1% in children < 2 yoa.50% of kids <1 yoa with UTI have VUREarly renal scarring is nearly twice as common in this age group.Incidence of scarring increases with each subsequent UTIScarring occurs in 5-38% of febrile UTI’s.
5Figure 1 Prevalence of VUR by age Figure 1 Prevalence of VUR by age. Plotted are the prevalences reported in 54 studies of urinary tract infections in children (references in Technical Report).Pediatrics 1999; 103:
6Figure 2 Relationship between renal scarring and number of urinary tract infections.16 Pediatrics 1999; 103:
7UTI: Classiffication Classification: Upper tract infection Acute pyelonephritis- fever, bacteriuria, systemic symptomsLower tract infectionUrethritisCystitisVoiding symptoms, little or no fever, no systemic symptoms
8Clinical Presentation Age and gender dependent0 - 2 months:Fever2 mo.– 2 y/o:Fever (>38 C)IrritabilityVomiting and DiarrheaDecrease appetiteBetween 1-2 y/o = crying on urination, foul smelling odorFemales of all ages are more predisposed to UTI due to short urethra.Male urethra as an infant is also short.What is the rationale for why a febrile UTI is pyelo until proven otherwise?The kidney is a complex organ as opposed to the bladder as a hollow viscus. Inflammation of the parenchyma of the kidney is responsible for fever.
9Clinical Presentation 2 y/o – 6 y/o:Systemic symptomsFeverFlank or back painUrgency, urinary incontinence, dysuriaSuprapubic or abdominal painFoul smelling odor> 6 y/o and adolescents:Same as above
10Urethritis In female infants In adolescent girls and boys Part of a diaper dermatitisIn adolescent girls and boysPresenting sign of STDIn pre-school and school age girlsPart of “non-specific” vulvovaginitisGenerally environmentalBubble bathNylon panties (also biker shorts, leotards, bathing suits)Poor hygiene (not wiping, wiping back to front)Overzealous hygieneUse of baby powder, perfumes
11Symptoms of urethritis DysuriaReluctance to voidPerineal discomfort, erythemaMay be associated with vaginal irritation and erythema in girlsIn older boys, urethral dischargeIn adolescent girls associated with PID symptomsSymptoms are difficult to elicit in younger children secondary to lack of vocabulary
12Cystitis Afebrile usually Frequency Enuresis Dysuria Reluctance to void
13PyelonephritisUsually associated with fever and systemic signs 2° renal parenchymal inflammationOlder childrenFlank pain or abdominal painYounger childrenFever, irritability, vomiting, poor feeding
14Pyelonephritis - Significance EACH infection results in scar formation and reduced renal functionAfter diabetes mellitus and collagen vascular disease, undetected renal disease and untreated childhood UTI may be responsible for:A large of portion of ESRD in adultsA huge need for dialysis and transplantationIt has been the assumption that renal scars are the RESULT of infection; could it also be that kidneys which are scarred or dysfunctional are at higher risk for infection? Is it an association or causality?
15Pyelonephritis - Significance Untreated childhood UTI responsible for:HypertensionImpaired kidney functionComplications of pregnancy
17Risk Factors Age <1 year Female gender Uncircumcised males ConstipationVoiding dysfunctionImproper wipingGenitourinary abnormalitiesVesicoureteral refluxObstructionColonization with virulent E. Coli
18Signs and Symptoms – Children 2 months to 2 years Fever—usually unexplainedVomiting and/or diarrheaAbdominal PainFailure to thriveMalodorous urineCrying on urination
19Signs and Symptoms – Children >2 FeverVomiting and/or diarrheaAbdominal painMalodorous urineFrequency and/or urgencyDysuriaNew incontinence
20SummaryUrinary 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 requiredUrine culture is required for diagnosis, and should be obtained by catheterization or SPA when child is ill or infection is suspectedTreatment requires a 7-14d course of antibioticsProphylactic abx are required after initial treatmentAll Children <2 require 2 imaging studies after initial UTI
21ReferencesCommittee 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:Layton, KL. Diagnosis and Management of Pediatric Urinary Tract Infections. Clinics in Family Practice 2003; 5: 2Chon DH, Frank CL, Shortliffe LM. Pediatric Urinary Tract Infections. Pediatric Clinics of North America 2001; 48:Linderd KA, Shortliffe LM. Evaluation and management of pediatric urinary tract infections. Urologic Clinics of North America 1999; 26:McCollough M, Sharieff G. Marx: Rosen’s Emergency Medicine: Concepts and Clinical Practice, 5th ed.2002;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
22Patient groups Options Time horizon NHS perspective long-term antibiotic treatment for preventing recurrent urinary tract infections (UTI) in childrenPatient groupsInfants of 1 yearGirls and boysRecurrent UTI (no abnormalities)Mild VUR (grade I and II)OptionsLong-term low dose antibiotics (Cochrane review)(Trimethoprim, Nitrofurantoin, Cotrimoxazole)Intermittent treatment of UTIsTime horizon3 years of long-term antibiotics and follow-up to end stage renal diseaseNHS perspective
24The evidence Effectiveness Existing reviews (variable quality) Meta analysis, Multiple parameter synthesisProbabilistic trial based modelNatural historyEpidemiological studiesPooled trial baselinesRegistry studiesClinical judgementQuality of lifePublished studiesSurveyCostsPublished unit costs and dosage (BNF, PSSRU, CIPFA)
25Antenatal 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.
29Pathophysiology: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.
34Urine CollectionClean Catch acceptable for toilet trained children (wearing underwear or pull-ups)Ensure cleansing with antiseptic toweletteCatheterized specimen in diapered childrenSuprapubic bladder tap in <6 month old child is guaranteed sterileFrequently, the nursing staff will need to give explicit instructions to parent or patient or actually assist in urine collection
35Leukocyte Esterase Has to accumulate in urine Insufficient accumulation possible in small infants who void frequentlyInfants <3 months old may not have mature enough immune system to induce leukocytes in urine (beware neutropenia on CBC)
36NitritesBy-products of E. coli and other lactose fermenters (glucose digestion)Insufficient accumulation possible in small infants who void frequentlyInsufficient accumulation possible in older child during the day and in older patient who has significant frequencyIf positive, highly suggestive of UTI (high specificity)
37Microscopy >10 WBC/hpf on spun urine Bacteria on unspun urine are common unless catheterized specimenGram stain is very helpful on spun urineStandard UA plus gram stain is “enhanced UA”Usually reported as “5-20” or “<5”…so what to do if you are looking for >10??
38Urine Culture >100,000 cfu per mL on any culture >10,000 cfu per mL on cath specimenANY bacterial growth on bladder tap (at least 1,000 cfu/mL)
39Sensitivity and Specificity of Components of the UASensitivity %(Range)Specificity %(Range)TestLeukocyte esteraseNitriteLeukocyte esterase or nitrite positiveMicroscopy: white blood cellsMicroscopy: bacteriaLeukocyte esterase or nitrite orMicroscopy positive83 (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)
40Urine Cultures Held for 48 h but usually positive at 24 h for true UTI Requires another day for ID of organismMay require another day for sensitivitiesIf contains skin flora (S. epi., S. aureus or α-strep.) considered contamination secondary to poor specimen collection
41DiagnosisUrinalysisCan be obtained by most convenient means if infant is not illUTI CANNOT be diagnosed with UA aloneIf suspicious UA, the Urine Culture must be obtained via SPA or catheter specimenIf UA does not suggest UTI, it is reasonable to follow child clinically
42Sensitivity % (Range) Specificity % (Range) Table 1. Sensitivity and Specificity of Components of the Urinalysis, Alone and in Combination (References in Text)TestSensitivity % (Range)Specificity % (Range)Leukocyte esterase83 (67-94)78 (64-92)Nitrite53 (15-82)98 (90-100)Leukocyte esterase or nitrite positive93 (90-100)72 (58-91)Microscopy: WBCs73 (32-100)81 (45-98)Microscopy: bacteria81 (16-99)83 (11-100)Leukocyte esterase or nitrite or microscopy positive99.8 (99-100)70 (60-92)Pediatrics 1999; 103:
43Diagnosis Urine Culture MUST be collected via catheter or SPA UTI CANNOT be diagnosed from a bag specimenDiagnosis of UTI requires Urine CultureLOE--Strong
44Urine Collection: Suprapubic Aspirate “Gold standard” - >99% specificityPositive culture: any number of g- bacilli or >3000 CFU of g+ cocci
47Treatment May initiate treatment either orally or parenterally Admit and use parenteral antibiotics if toxic, dehydrated or unable to take POChoices:TMP/SMXCephalosporinAmoxicillin (check local resistance)
48Treatment--continued Improvement should be seen in hoursIf not having expected clinical response in 2 days, re-culture, consider changing antibiotics and do imaging studiesComplete 7-14 day course of antibiotics14 days should be given for those that were ill with clinical evidence of pyelonephritis
49ProphylaxisAfter completion of initial antibiotics, children should be give a prophylactic dose of antibiotics until imaging studies completeAntibiotic should have high urinary excretion and low serum and fecal levels, thus minimizing the development of resistance.
50ImagingNeeds to be performed in ALL children <2 years old with initial UTINeed to perform at least 2 studies to image the upper and lower urinary tractsAcute imaging only necessary when appropriate clinical response is not achieved within 2 days
51UltrasoundShould be done on all infants < 2yoa after their initial UTIHelps to detect hydronephrosis and ureteral dilationHas replaced IVPNeed additional study to evalute VURIs not as sensitive as renal cortical scintigraphy (DMSA) for detecting inflamation and scarring
52Voiding Cystourethrography (VCUG) Used to identify and grade refluxAlso evaluates the urethra and bladder for abnormalities – important for boys who may have posterior urethral valves and girls with voiding dysfunctionRadionuclide 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
53Renal Cortical Scintigraphy (DMSA) Very sensitive for evaluating acute inflammation from pyelonephritis as well as renal scarringRole in clinical management is still unclear
54Treatment No “short course” therapy for small children No “short course” therapy for malesEmpiric therapy is directed at organisms and adjusted for age.Choose narrowest spectrum allowable considering host factorsAdjust therapy when sensitivities availableShort course is NOT indicated for pyelonephritis but a recent study suggests it is acceptable in cystitis in childrenArch Dis Childhood 2002 August 87 (2) :
55IV antibiotics-Indications Any person of any age who appears clinically toxic or who has neutropeniaInfants <1 mo until bacteremia, sepsis, & meningitis ruled outChildren unable to tolerate oral antibioticsImmunocompromised patientsMultiple studies show NO benefit to outcome for children treated parentarelly vs orally.Arch Pediatr Adol Medicine 2001 Feb 155(2), “The addition of ceftriaxone to oral threapy does not improve outcome in febrile children with urinary tract infections.J Chemother, 2001, June:13(3): Comparative study of cefixime alone vs. intramuscular ceftizoime followed by cefixime in the treament of urinary tract infections in children
56Antibiotic choice Neonates Ampicillin plus a second antibiotic (usually gentamycin or cefotaxime) to cover for GBS, Listeria, as well as gram negative organismsS. 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
57TherapyCefixime (Suprax) oral is as effective as parenteral ceftriaxoneCefpodoxime (Vantin)Bad tasting10 mg/kg/dayFluoroquinolones are expensive and ”off label” in pediRationale is to cover for fecal coliforms which are usual culprits Need to be cognizant of local organisms; there is literature that supports the idea that Bactrim may be facing increasing levels of resistance in UTI organisms; fluoroquinolones may soon be approved for children less than 12 but are more expensive than most cephalosportinsJ Chemother Jun;13(3):Related Articles, LinksComparative study of cefixime alone versus intramuscular ceftizoxime followed by cefixime in the treatment of urinary tract infections in children. Gok F, Duzova A, Baskin E, Ozen S, Besbas N, B
58Bacterial virulence Bacterial spectrum at the Ist Dept Bacterial virulence Bacterial spectrum at the Ist Dept. of Pediatrics, inN= (%)E. coliEnterococcus faecalis 13Proteus indol neg. 10KlebsiellaPseudomonas spp 7Enterobacter spp 6Proteus indol pos 3StaphylococcusOther
59Sensitive host Age related factors Anatomy (short urethra, phymosis and adhesio cellularis preputii et labia minora, diaper)colonizationImmunological susceptibilityMucosal barrierInherited/acquiredimmunresponseEx: IgA deficiency, P1 blood group
64UTI Controversy #1: Antibiotic Prophylaxis Indications grade 1 VURfrequent UTI recurrencesProblemsPt Rxd with antibiotic prophylaxisIncreased infection with Proteus and Enterobacterpseudomonas and Candida increased in children with urogenital abnormalitiesDrug toxicity and sensitivitiesAntimicrobial choices (qhs better)TMP-SMX or Nitrofurantoin (GI disturbance)Keflex if < 3 monthsQuinolones in some circumstances
65Posterior 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.
66Radiographic signs of PUV: distended prostatic urethravalve leafletsbladder and/or bladder neck hypertrophydiverticulanarrow stream in the penile urethraincomplete emptying of the bladder
67Treatment of PUV:Transurethral valve ablation, vesicostomy or upper tract diversionUrethral stricture is a common complicationFetal intervention carries a high risk with mortality rate of 43%ESRD, renal insufficiency and chronic renal failure are long-term consequences
6830% of boys with posterior urethral valves whose symptoms present in infancy are at risk for progressive renal insufficiency.
75Vesicoureteral 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.
76The 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.
78Some 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.
81Prognosis: Resolves spontaneously before adolescence in: 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.Resolves spontaneously before adolescence in:90% of Gr. 1 reflux80% of Gr. 250% of Gr. 310% of Gr. 40 in Grade 5 reflux
82Treatment: Observation Medical treatment of infections Surgical treatmentsignificant hydroureteronephrosisindicated if impossible to keep urine sterile and reflux persistsacute pyelonephritis occursevidence of increasing renal damage
88Bacterial virulenceVirulence=factors that enable bacteria to invade the urinary tractSurface antigenesO: lipopolysacharides with endotoxin properties. Induces fever, local inflammationK, (capsular) antigene, prevents phagocytosis“P” fimbriae: bind to glycolipid receptors of the P blood group familyA number of further factors not routinely checked