Pediatric Urinary Tract Infection Biology Essay

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Although all individuals are susceptible to UTI, most remain infection free during childhood because of the innate ability to resist uropathogen attachment. There are specific subpopulations with an increased susceptibility to UTI,

Neonates and infants in their first few months of life are at a higher risk for UTI. This susceptibility has been attributed to an incompletely developed immune system. Breastfeeding has been proposed as a means of supplementing the immature neonatal immune system via the passage of maternal IgA to the child, providing the presence of lactoferrin, and providing the effect of anti-adhesive oligosaccharides. Several recent studies have demonstrated the protective effect of breastfeeding against UTI in the first 7 months of life.56

3.5.1.2UNCIRCUMCISED INFANT BOYS

Since the 1980s, studies have shown an increased frequency of UTI in uncircumcised boys during the first year of life22. Boys with foreskin tend to harbor significantly higher concentrations of uropathogenic microbes that potentially may ascend into the urinary tract and lead to UTI .Bacteuria is much more common during the first 6 months of life for uncircumcised boys

3.5.1.3 FECAL AND PERINEAL COLONIZATION

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Because most UTIs result from fecal-perineal-urethral retrograde ascent of uropathogens, fecal and perineal flora are important factors in the development of a UTI42. The flora of the colon and urogenital region is a result of native host immunity, existing microbial ecology, and the presence of microbe-altering drugs and foods. A recent investigation by Schlager and colleagues 41supported the theory that a subset of the colonic microflora expressing particular virulence factors is most likely to infect the urinary tract. The selection for microbes resistant to antimicrobial agents is well recognized. As a result, the inappropriate use of antibiotics in the treatment of active nonurinary infections and in the prophylactic setting may place children at a higher risk for developing uropathogenic strains of microbe that may develop into symptomatic UTI.

3.5.1.4ANATOMIC ABNORMALITIES

Anatomic abnormalities of the urinary tract predispose child to UTI because of inadequate clearance of uropathogens. Infections associated with urinary tract malformation generally appear in children younger than 5 years of age. It is essential to identify these abnormalities early because if uncorrected they may serve as a reservoir for bacterial persistence and result in recurrent UTI. Surgical intervention may be required to correct the anatomic abnormality.

However, congenital anatomic anomalies, such as posterior urethral valves and subsequent vesicoureteral reflux (VUR), do not predispose children to colonization but perhaps increase the likelihood of inadequate washout in the routine ways. These urinary tract malformations increase the likelihood that infections of the lower urinary tract (ie, bladder and urethra) will ascend to the upper tracts with possible pyelonephritis and potential renal deterioration. Children with known urinary malformation may be on chronic antimicrobial prophylaxis. Consequently, this patient population is associated with a higher incidence of multidrug-resistant uropathogens and non-E coli uropathogens, particularly Pseudomonas and Enterococcus.

3.5.1.5FUNCTIONAL ABNORMALITIES

Children with a functional abnormality of the urinary tract are also at a higher risk of developing a UTI. Inability to empty the bladder, as in the case of neurogenic bladders, frequently results in urinary retention, urinary stasis, and suboptimal clearance of bacteria from the urinary tract. Clean intermittent catheterization is helpful for emptying the neurogenic bladder, but catheterization itself may introduce bacteria to this normally sterile space. Chronically elevated bladder pressure secondary to poor emptying also may cause secondary VUR, in which the elevated pressure increase the potential renal damage of pyelonephritis.

CLINICAL PRESENTATION

Children with UTI do not present with the characteristic signs and symptoms compared to adult population. There are various clinical presentations for children with UTI based on age. Infants younger than 60 to 90 days may have vague and nonspecific symptoms o illness like failure to thrive, diarrhea, irritability, lethargy, malodorous urine, fever asymptomatic jaundice, and oliguria or polyuria57,58,59 In fact, it has been recommended that testing for UTI be part of the evaluation of asymptomatic jaundice in infants younger than 8 weeks.59

In children less than 2 years of age, common symptoms include fever, vomiting, anorexia, and failure to thrive58. In children between 2 and 5 years of age abdominal pain and fever were the most common symptoms 60. Children at 5 years of age symptoms include dysuria, urgency, urinary frequency, and costovertebral angle tenderness, are more common60. As a result, UTI must be considered in all children with serious illness even if there is strong evidence of infection outside the urinary system. .Vesico urethral reflex(VUR) seen more in children than infants with UTI .

DIAGNOSIS OF URINARY TRACT INFECTION

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The diagnosis of urinary tract infection is based on culture of a properly collected specimen of urine. Urine analysis is helpful in providing immediate information to suspect urinary tract infection and enable initiation of treatment.

URINE CULTURE

The detection of significant numbers of pathogenic bacteria from culture of the urine has remained the gold standard for the diagnosis of urinary tract infection since Kass defined > 105 CFU/ml of a single pathogenic bacterium isolated from urine culture as being significant in women with pyelonephritis or asymptomatic bacteriuria.61

The specimen for urine culture should be obtained carefully to prevent contamination, Washing the genitalia of the child with soap and water minimizes contamination. The urine specimen for culture can be obtained in following ways.

Suprapubic aspiration

Urethral catheterization

Clean catch midstream urine

Suprapubic aspiration has been consider the “gold standard” for obtaining urine as it is least likely to be contaminated. Urine obtained by transurethral bladder catheterization is next best. A clean-catch midstream urine specimen is most widely used.

Prompt plating of urine specimen within 1 hour of collection is important. The specimen is inoculated into blood agar and MacConkey media and incubated for 24 hours to obtain an accurate colony count

INTERPRETATION OF URINE CULTURE

Method of Colony count Probability of

Collection Infection (%)

Suprapubic Any number of 99%

Aspiration pathogens

Urethral >50 x 104 CFU/ml 95%

Catheterization

Midstream clean >105CFU/ml 90-95%

catch

3.7.2 URINE ANALYSIS

Urinalysis done on a fresh urine sample, can identify children with a high likleihood of a urinary tract infection. Several rapid screening tests are commonly used. Urinalysis may show

1) leukocyturia

2) bacteria on gram stain

3) Positive leukocyte esterase and nitrite test by dipstick

3.7.2.1PYURIA

The most accurate method of measuring pyuria is to measure urinary leucocyte excretion. An excretion rate of 4,00,000 leukocytes / hours or greater correlates with symptomatic urinary tract infection.62 The presence of >5 pus cells / high power field in a centrifuged sample or >10 pus cells / mm3 in an uncentrifuged sample is diagnostic of urinary tract infection

3.7.2.2 BACTERIURIA

Direct microscopy for the detection of baceteriuria is a readily available but highly variable method of determining bacteria. Jenkins et al63 determined that uncentrifuged gram-stained urine that revealed atleast one organism per oil immersion field correlated with >105CFU / ml urine with sensitivity and specificity of almost 90%. Additionally, finding five or more organisms per oil immersion field increased the specificity to 99%. It was also found that, the use of unstained, centrifuged urine is a convenient and reliable method of determining significant bacteriuria, but the method was most reliable only when 106CFU / ml or greater were isolated by culture.

A rapid diagnostic test for the detection of bacteriuria, the nitrite test, is both widely available and easily performed. The test is performed by the dispstick method, which utilizes an amine - impregnated pad to detect the presence of urinary nitrate. Nitrite in the urine is produced by the action of bacteria on dietary nitrate through nitrate reductase, a bacterial enzyme, The presence of urinary nitrite is indicated by the development of a pink colour on the pad within 60 seconds.

False negative assays may be the result of

1. The lack of dietary nitrate

2. Insufficient urinary nitrate levels due to diuretics.

3. Infection due to an organism that is unable to produce nitrate in the urine through a lack of nitrate reductase.

Eg. : Staphylococcus sp.

Enterococcus Sp.

Psuedomonas Sp.

3.7.2.3 SENSTIVITY AND SPECIFICITY OF TESTS USED TO DIAGNOSE URINARY TRACT INFECTION64,65

Chemical Sensitivity Specificity

1. Nitrite 30-90% 90 - 95%

2. Leukocyte esterase 50-75% 80%

Microscopic

1. Urinalysis (Pyuria) 30-80% 30-80%

2. Gram stain (Bacteriuria) 90% 90%

Microbiologic

1. Clean catch 80-98% 80%

2. Catheterization 90-95% 80-90%

3. Suprapubic aspiration >95% >98%

IMAGE STUDIES

The goal of imaging studies in children with a urinary tract infection is to identify abnormalities that predispose to infection.

A renal ultrasonogram should be obtained to rule out hydronephrosis and renal or perirenal abscesses; ultrasonography may also show acute pyelonephritis by demonstrating an enlarged kidney. Ultrasonography demonstrates 30% of reanl scars, Renal ultrasonography is also sensitive for detecting pyonephrosis, a condition that may require prompt drainage of the collecting system by percutaneous nephrostomy. Sonography is insensitive in detecting reflux. A voiding cystourethrogram (VCUG) is indicated in all children younger than 5 years with a urinary tract infection, any child with a febrile urinary tract infection, school aged girls who have had two / more urinary tract infections, and any male with a urinary tract infection. The most common finding is vesicoureteral reflux, which is identified in approximately 40% of patients When the diagnosis of acute pyelonephritis is uncertain, renal scanning with technetium labelled Dimercaplosuccinic acid scan (DMSA) or glucoheptonate is useful. The presence of parenchymal filling defect on the renal scan supports the diagnosis of pyelonephritis but may not differentiate an acute from a chronic process. DMSA scan shows a filling defect in approximately 50% of children with a febrile urinary tract infection, irrespective of age. In children with grade III, IV or V reflux, 80-90% of patients with a febrile urinary tact infection have a focal defect. The DMSA scan is considered the most sensitive and accurate study for demonstrating scarring. Computed tomography is another diagnostic tool that can diagnose acute pyelonephritis.

MANAGEMENT

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Treatment should be started after obtaining a urine culture ,childs age,activity ,state of hydration and ability to take orally , help in deciding between outpatient treatment and hospitalization.

In infants less than 3 years of age complicated urinary tract infection are treated with parenteral antibiotics. A combination of Ampicillin and Gentamicin or a third generation cephalosporin is preferred. Antibiotics may be administered orally once the condition of the child improves .Infants and children with a positive blood culture should receive parenteral anibiotics for the entire duration of treatment.

Oral medications are used in children above 3 months of age with a simple urinary tract infection. The duration of treatment is 10-14 days for infants and children with complicated urinary tract infection and 7-10 days for uncomplicated urinary tract infection . Imaging of urinary tract is recommended for all children with urinary tract infection.

MANAGEMENT OF FUNGAL URINARY TRACT INFECTION

Although fungus in the urinary tract is rare among healthy children, the incidence of fungal UTI is increased in hospitalized patients. In large tertiary care neonatal intensive care units, Bryant and colleagues66 found the overall incidence of candiduria to be 0.5%, whereas Phillips and Karlowicz33 reported Candida sp in 42% of patients with UTI. Risk factors for the development of funguria include long-term antibiotic treatment, use of urinary drainage catheters, parenteral nutrition, and immunosuppression. The overwhelming majority of fungal UTIs are caused by Candida sp followed by Aspergillos spp, Cryptococcus spp, and Coccidioides spp. The clinical presentation of patients with funguria ranges from an absence of symptoms to fulminant sepsis. Urine cultures with more than 104 colonies/mL have been used as the criterion for therapy67. The presence of a positive urine culture result mandates an evaluation of the upper urinary tract with renal ultrasonography for additional foci of funguria. Renal fungal balls have been identified in 35% of patients with candidal UTI in the pediatric population33,66. Symptomatic patients can be treated with bladder irrigations of amphotericin B or oral fluconazole. Although there is no consensus on optimal treatment dose or duration, amphotericin bladder irrigations consist of daily irrigations of 50 mg/L for 7 days or continuous irrigations (42 mL/h) for 72 hours. Fungal bezoars in the collecting system may cause obstruction in children. Patients with these upper tract foci of funguria should be treated with systemic therapy that consists of amphotericin B or fluconazole. In cases of obstruction, percutaneous nephrostomy is then used for drainage and potential local irrigation. Surgical removal may be necessary should the fungal balls persist.

LONG TERM CONSEQUENCES OF PEDIATRIC URINARY TRACT IN FECTION

Children with upper UTI (ie, pyelonephritis) are at risk for irreversible renal parenchymal damage as evidenced by renal scarring. Renal scarring is noted in 10% to 30% of children after UTI 68,69. The most widely used method of detecting renal scarring is 99Tc-labeled dimercaptosuccinic acid scintigraphy scan. Although the exact mechanisms responsible for renal scarring secondary to UTI are currently unclear, risk factors include underlying VUR or obstructive urinary tract abnormalities and recurrent UTI and a delay in treatment of UTI. A recent study by Orellana and colleagues 70 found a significantly higher incidence of renal damage in children with nonâ€"E coli UTI. Smellie and colleagues35 found renal scarring more commonly in infants and young children and less frequently in older children and young adults, which suggests that younger kidneys are more susceptible to damage.

First Urinary Tract Infection

Age < 1 yr Ultrasound MCU

DMSA renal scan

Age 1-5 yr Ultrasound DMSA scan

Age> 5 yr Ultrasound

MCU if ultrasound or DMSA scan is Abnormal

If ultrasound abnormal: MCU and DMSA scan