I.Introduction
Urinary tract infection(UTI) is characterized by the multiplication rate of microorganisms (mainly bacterium) in any segment of the urinary tract.Its importance is related to many aspects:
. Frequency of occurence in Pediatrics (corresponds to 5%of ambulatoryal complaints). UTI is the most common serious bacterial illness among febrile infants and young children. Risk in the first 11 years of life for boys and girls is 1% and 3%, respectively. About 40% of these children will have recurrent infections.
. Many times UTI is not an isolated fact, it is a manifestation of an underlying condition (vesicoureteral reflux, neurogenic bladder, vesical instability,...).
. If not treated properly, UTI can result in renal scarring and even insufficiency.
. 24% of children with renal scarring due to infection caused by reflux will present arterial hypertension in the future.
II. Etiology
Gram-negative bacteria:
- Escherichia coli (80% of cases)
- Klebisiella pneumoniae
- Proteus mirabilis
- Enterobacter aerogenes
- Pseudomonas aeruginosa
- Serratia marcensces
- Salmonella
Gram-positive bacteria:
- Staphylococcus epidermidis
- Enterococcus
- Staphylococcus aureus
- Staphylococcus saprophyticus
Another agents:
- Adenovirus type 11 and 12
- Candida albicans
The gram-negative bacteria are the most common pathogen and among them E. Coli causes most of the acute UTIs. The other gram-negative bacteria (Proteus, Pseudomonas and Klebisiella) are probably related to chronic infections and/or repeated infections. Bacteriuria by Salmonella is generally related to sepsis by Salmonella.
The gram-positive bacteria are also cause of UTI. Staphylococcus coagulase-negative are detected as pathogens of urinary tract in young women who are sexually active and in newborns. These microorganisms can reach the urinary tract by the hematogenic pathway.
Adenovirus type 11 and 12 are related to acute hemorrhagic cystitis. Candida albicans can cause UTI in patients manipulated by catheters or in immunodefficiency.
III. Sex and frequency
In childhood, UTI is more frequent in girls (from 4 girls:1boy to 20 girls:1 boy), but in the first year of life it is more frequent in males.
A. ASYMPTOMATIC BACTERIURIA
UTI may be asymptomatic at any age. Up to 2/3 of preschool and school-aged girls may be symptom free with their first UTI. In girls with asymptomatic bacteriuria E. Coli is not able to attach the urinary tract and is sensitive to the high bactericidal capability of the plasm. Because of that, most of the studies suggests that asymptomatic bacteriuria may not be treated, since a therapy can lead to antibiotic resistence and reinfection.
B. CYSTITIS see clinical manifestation
C. PYELONEPHRITIS see clinical manifestation
The ascendent pathway (via urethra) is the most important pathway at all ages, except in the newborn in which the hematogenic pathway is the main one.
There are many factors related to the microorganism and to the host in UTI pathogenesis:
. Host-parasite interactions and genetic influences
E. Coli binds to glycolipid and glycoprotein receptors on the surfaces of uroepithelial cells via various adhesins, especially the genetically related P and F adhesins. The carbohydrate compositions of glycolipids such as ABO, P and Lewis antigens, are determinated by the synthetic activity of genetically controlled glycosyltransferases. Thus, inheritance of the gene that encodes the glycosyltransferases influences the cell surface glycolipid composition of tissues in which the gene is expressed.
In the pediatric population, the P1 blood group phenotype has been associated with increased risk of recurrent pyelonephritis.
After E. Coli adherence to epithelial cells, E. Coli transfers toxins and endotoxins to the host, resulting in the effects below:
. Ureter peristalsis paralysation
. Consequent ureter dilatation
. Decrease in mitotic activity of the vesico-ureteral junction cells
. Inflamatory response: - fever
- reactive C protein
- VHS
- leukocytosis
Predisposing factors related to the host
1.Vesicoureteral reflux
Increases the risk of pyelonephritis, occuring in 30-50% of the cases, principally in young children. In these cases E. Coli does not need virulence factors to determine renal scarring.
2. Obstruction
Leads to urinary stasis and facilitates bacterial adhesion (remember that urine is a good culture medius !)
Eg.: stenosis, fistula, calculus, valvule
3. Female short urethra
facilitates the ascendent via of infection.
4.Bladder disfuction
Vesical instability and neurogenic bladder may function as urinary tract obstruction and leads to stasis and infection.
5.Intestinal constipation
Fecalomas may alter urinary voiding by compression, leading to stasis and infection.
6.Colonization of glans and foreskin
In glans and foreskin E. Coli the receptors density is increased.
7.Instrumentation (catheterization)
Increases the risk of the UTI.
8.Previous antibiotics administration
can lead to drug resistance and clonal expansion of resistent bacteria.
Protective factors related to the host
1.Circumcision
There is a relationship of lack of circumcision to an increased risk of UTI, that was first noted among infant boys in 1982. The risk increases in 2,5-fold in UTI in uncircumcised boys aged to 1 to 14 as compared with circumcised boys of the same age.
2.Periodic and complete urinary voiding
decreases risk of UTI because prevents stasis.
3.Satisfactory hydric regimen
increases frequency of micturition leading to urinary voiding.
4. Low pH
The acid vaginal pH is an important fact to the lack of colonization. Low pH has an inhibitory effect on P. mirabilis and P. Aeruginosa, may be it explains the high incidence of UTI caused by E. coli.
5.Inespecific mecanisms of the mucosa mediated by eletrostatic forces
Risk groups for bacteriuria or symptomatic UTIs with subsequent renal damage include:
1) premature infants discharged from neonatal intensive care units
2) children with systemic or immunologic diseases
3) children with urinary tract abnormalities, renal calculi, neurogenic bladder, voiding disfunction, constipation or a family history of UTI with abnormalities such as reflux
4) girls younger than 5 years with a previous history of UTI
5)uncircumcised males: increased risk of UTI
VI. Clinical Manifestation
<2 years of age: - FEVER (we must ask for uroculture at this age in case of fever because in this group, most of the UTI corresponds to pyelonephritis)
- failure to gain weight
- prostration
- gastrointestinal disfunction
- vomiting
- jaundice
- local symptoms are very rare
Bacteriuria may be the first sign of infection.
>2 years of age: pyelonephritis
- high fever
- toxicity
- flank pain
- costovertebral angle tenderness
cystitis- suprapubic pain
- dysuria
- frequency
- urgency
- enuresis
Localization of the site of infection may be very difficult, specially in young children
VI.Diagnosis
- Microscopic urinalysis
It has poor predictability of abnormal urinalysis. It may be normal, so it is not used for UTI diagnosis neither treatment. In other cases it may be abnormal and does not correspond to an UTI (eg.: piuria can occur in glomerulonephritis without UTI).
- Urinoculture
Gold-standard for UTI diagnosis. Bacteria grown from a urinoculture may arise from:
(1) contamination outside of the urinary tract
(2) colonization of the distal urethra (contamination from within the urinary tract)
(3) asymptomatic colonization of the bladder urine
(4) true urinary infection
Due to the factors above, we must be careful in collecting the urinary specimen.
If the urinary specimens are obtained with use of a plastic bag attached to the perineum, even after extensive cleaning these specimens may more often reflect perineal and rectal flora and are mainly useful if they grow few or no organisms. Although midstream-voided specimens in older girls, circumsided boys, and older boys whose foreskin is easy retracted may be fairly reliable for culture, these same specimens obtained in young girls and uncircumsided boys may reflect periurethral and preputial skin bacterial colonization.
When cultures are difficult to interpret and there is a doubt that the child is actually experiencing infections, reliable specimens taken by suprapubic aspiration or urethral catheterization when the child is symptomatic are needed to clarify the situation.
An urine culture should be obtained 1 week after therapy has been initiated, and at this time the urine should be sterile.
VIII. Imaging studies
Imaging studies are part of standard care after diagnosis of UTI in young children. Indications for radiologic evaluation of a child with UTI are:
(1) pyelonephritis
(2) first UTI in a boy (of any age)
(3) first UTI in a girl younger than 3 years of age
(4) second UTI in a girl 3 years of age or older
(5) first UTI in a child (of any age) with a family history of UTIs, abnormalities of the urinary tract, an abnormal voiding pattern, hypertension or poor growth.
The aim of these imaging studies is detect urinary tract morphologic/functional alterations and children at risk of renal damage.
Young child and UTI duration are important factors related to the renal damage extension. The pyelonephritic scarring can result from a UTI,mainly at the first two years of age.
Urinary tract abnormalities can be found, mainly vesicoureteral reflux, alteration that is highly associated with UTI. Vesicoureteral reflux can be tenuous (I and II levels), moderate (III level) or severe (IV and V levels). V level is characterized by pyelotubular (intrarenal) reflux that damages renal parenchima, leading to progressive and irreversible deterioriation. It is important to observe that not always there is a relationship between reflux level and renal damage (pyelonephritic scarring).
Which study we might ask ?
.Intravenous Urography(IVU)
- good for obstruction detection
- good for pyelonephritic scarring ( does not detect recent scars)
. Voiding cystourethogram
- excellent for vesicoureteral diagnosis
- excellent for infrabladder obstructions
- identify vesical capacity and its wall morphology
. Renal and bladder ultrasonogram
- good resolution for liquid colections (abcess, cysts,...)
- good resolution for calculi (> 0,5cm)
- low specificity and sensibility in acute pyelonephritis and pyelonephritic scarring detection
.Urodynamic Evaluation
- it's indicated in patients with micturition alteration (urinary incontinence, infravesical obstruction, neurogenic bladder) which can lead to UTI because occurs an inadequate voiding bladder and urie stasis. Besides bladder disfunction causes vesical pression elevation,consequently increases vascular permeability and facilitates macromolecules passage from the lumen to the vesical wall.
.Dimercaptosuccinic acid nuclear scan (DMSA)
- best method for acute pyelonephritis diagnose and posible evolution of pyelonephritic scarring. Radiopharmac low-captation indicates proximal tubular disfunction and/or blood flux obstruction.
- alteration in this exam means renal involvement which can be transitory (acute pyelonephritis) or permanent (pyelonephritic scarring).
.Renal Dynamic Study using DTPA (dietilenotriaminepenta-acetic acid)
evaluates renal function (statics and dynamic), through concentration and excretion capacity of each kidney.
VIII. Therapy
General measures:
1- Familiar orientation
2- Estimulate adequate urinary rhythm (hydric ingest)
(micturition with intervals of 3/3 hs.)
3- Estimulate intestinal rhythm
ANTIBIOTIC THERAPY:
- Uncomplicated UTIs (oral treatment for 7-10 days)
. Nitrofurantoin: 1mg/kg/dose, 3 doses a day.
Low resistence, best for treatment, good tolerability.
Adverse effects: gastric intolerance, transitory leukopenia
.Nalidixic acid: 30-50 mg/kg day divided in 3 or 4 doses a day.
Adverse effects: hypersensibility, blood dyscrasia
.Sulfamethoxazole-trimethoprim: 6 mg/kg/day TMP and 40 mg/kg/day SMX divided in 2 doses a day.
High level of treatment failure.
.Ampicillin: 100-200 mg/kg/day divided in 3 or 4 doses a day.
Adverse effects: diarrhea - exanthema
.Cephalosporins (second-generation)
- Pyelonephritis / sepsis / UTI resistent to oral treatment (IM or IV therapy)
. Aminoglycosides
. Cephalosporins (third-generation)
. Norfloxacin/Ciprofloxacin
IX. Follow-up of a UTI and Prophylaxis
Follow-up of a UTI should be carefully organized, because infection tends to recurs, often in asymptomatic form. Recurrence is most likely after the first 6-12 month after an infection.
A) after therapy is discontinued, urinocultures are indicated 1 week later, every month during the subsequent 3 months, every 3 months during the next 6 months, and then twice a year.
B) among patients with siginificant vesicoureteral reflux, recurrent infection is prevent by antibiotic therapy.
C) in recurrent infections (at least 2 in 6 months) antibiotic prophylatic therapy is indicated.
Antibiotic prophylatic therapy
(1/4 of treatment dose - unique dose at night)
.Nitrofurantoin: 1-1,5 mg/kg/day
.Sulfametoxazole: 10 mg/kg/day
.Trimethoprim: 2mg/kg/day
Newborn:
. Trimethoprim: 2 mg/kg/once a day
. Cephalexin: 12,5 mg/kg/once a day
Special Thanks to Lucia Maria Costa Monteiro, MSc, PhD
Bibliography:
1. HELLERSTEIN STANLEY: Evolving concepts in the evaluation of the child with a urinary tract infection. The Journal of Pediatrics 1994, 124:589-92.
2. HOBERMAN A, WALD E R: Urinary tract infection in children. Pediatr Infec Dis J 1997, 16:11-7.
3. REESE E R , BETTS R F: A practical aproach to infectious diseases. Little, Brown and Company, 4th Edition, 1996.
4. SANGIACOMO LÚCIA: Revisão da investigação urinária recorrente em crianças. Como são abordadas aquelas que apresentam trato urinário normal? . Monography presented in July, 1996, at Fernandes Figueira Institute, Rio de Janeiro, BR.
5. SAUNDERS CE, HO M T: Current: Emergency diagnosis & treatment. Lange, 4th Edition, 833-835,1992.
6. SHORTLIFFE LMD: The management of urinary tract infections in children without Urinary tract abnormalities. Urologic Clinics of North America 1995, vol22, n1:67-73.
7. SPACH DH, STAPLETON AE, STAMM VE: Behavioral and genetic factors related to urinary tract infection. Current Opinion in Infectious diseases 1993, 6:31-35.
8. TOPOROVSKI J, GUIDONI EBM: Infecção do trato urinário na infância. Atualização. Temas de Pediatria, Nestlé; n64, 1996.
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