Urinary Tract Infection in Children - Classification, Diagnosis and Treatment

By Marco Zaffanello

Urinary tract infection (UTI) is common in children with a febrile infection. Although its frequency is high in pediatric age, it may be difficult to recognise in younger than 3 year-old patients because the presenting symptoms and signs are not specific. More commonly, UTIs are due to bacterial infections. The natural history of UTIs in children has ameliorated by improved healthcare facilities, including diagnosis, treatment and follow-up. UTIs are an important risk for long-term renal sequels when they are associated with urinary tract malformation. Appropriate diagnosis and treatment prevent complications such as hypertension, proteinuria and end stage renal disease.

• Language: English
• Publisher: Lulu.com
• Release date: May 11, 2015
• ISBN: 9781326272159

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Bibliography

About the Author

Marco Zaffanello, MD, Pediatrician, University Researcher, Department of Life and Reproduction Science, University of Verona, Verona, Italy, published several papers indexed in Pubmed, Embase and OVID electronic databases. Is a co-author in book chapters (Nephrology and Fluid/Electrolyte Phsiology: Neonatology Questions and Controversies, Elsevier Inc 2008 and updated in 2011; Thrombosis: Causes, Treatment and Prevention, NOVA Publishers 2010; Combating Fungal Infections. Problems and Remedy, Springer-Verlag 2010; A Practical Approach to Neonatal Management, by Giuseppe Buonocore, Rodolfo Bracci, Michael Weindling Editors, Springer Verlag, 2012). He contributed in the revision of many papers from important scientific journals.

About the book

Urinary tract infection (UTI) is a common reason of febrile infection in paediatric age. Although its frequency is high in children, it may be difficult to recognise a UTI in younger than 3 year-old because the presenting symptoms and signs are not specific. More commonly, UTIs are due to bacterial infections.

At the beginning of the 1900s there was approximately 20% of mortality in infants hospitalised for acute pyelonephritis. In developed countries, the natural history of UTIs in children has ameliorated by improved healthcare facilities, including diagnosis, treatment and follow-up. In developing countries, UTIs are not reported as a cause of morbidity, probably due to lack of overt clinical features in younger children, appropriate collection of urine samples and basic diagnostic tests at first level health facilities. Collecting urine and interpreting results are not easy in this age group, so it may not always be possible to confirm the diagnosis, with underestimation of the overall problem and morbidity.

In the past, UTIs have been reported as an important risk factor for the development of long-term sequels such as renal failure or end-stage renal disease. Actually only a minority of children with renal insufficiency have a history of UTIs. Therefore, UTIs are an important risk for long-term renal sequels when they are associated with urinary tract malformation. Major long-term consequences of recurrent UTIs are renal scarring, hypertension and renal failure. Rarely, recurrent UTIs have associated with end-stage renal disease. The better recognition of the UTIs and prompt diagnosis and therapy leaded a reduction of the rate of patients developing long-term renal complications.

Abbreviations

AAP             American Academy of Pediatrics

ABU             Asymptomatic bacteriuria

APN             Acute pyelonephritis

AUA             American Urological Association

BSA             Body surface area

CDS             Color Doppler sonography

CFU             Colony forming unit

CKD             Chronic kidney disease

CRF             Chronic renal failure

CRP             C-reactive protein

CS             Cystosonography

CT             Computed tomography

DMSA             Dimercaptosuccinic acid

DTPA             Diaminotetra-ethyl-pentacetic acid

ee-CS             Echo-enhanced cystosonography

EP             Emphysematous pyelitis

EPN             Emphysematous pyelonephritis

ESR             Erythrocytes sedimentation rate

ESRD             End-stage renal disease

ESRF             End-stage renal failure

GFR             Glomerular filtration rate

HSP             Heat shock protein

ICAM             Intercellular adhesion molecule

ILs             Interleukins

IL-1Ra             Interleukins-1 receptor antagonists

IVU             Intravenous urography

LPS             Lipopolysaccharide

MAG3             Mercaptoacetyltriglycine

MCP-1             Monocyte chemotactic peptide-1

MMP-9       Matrix metalloproteinase-9

MRI             Magnetic resonance imaging

NF-kB             Nuclear factor-kB

NICE             National Institute for Health and Clinical Excellence

NICU             Neonatal intensive care unit

NO             Nitric oxide

PCT             Procalcitonin

PECAM-1       Platelet endothelial cell adhesion molecule-1

PUJ             Pelvic-ureteric junction

PUVs             Posterior urethral valves

RAS             Renin-angiotensin system

RBCs             Red blood cells

RIVUR       Randomized intervention for children with vesicoureteral reflux

RR             Relative risk

TGF-β             Transforming growth factor-β

TIMPs             Tissue inhibitors of metalloproteinases

TLRs             Toll-like receptors

TNF-α             Tumor necrosis factor-α

UPJO             Ureteropelvic junction obstruction

US             Ultrasonography/Ultrasound

UTIs             Urinary tract infections

VCUG             Voiding cystourethrography

VUJ             Vesicoureteric junction

VUR             Vesicoureteral reflux

WBCs             White blood cells

Chapter 1.

CLASSIFICATION AND DEFINITION

According to the localization of the infection, the two main forms of symptomatic UTIs are acute pyelonephritis (APN) and cystitis, which involve either higher or lower urinary tract, respectively. Asymptomatic bacteriuria (ABU) defines the localization of the bacteria along the urinary tract without giving a true infection. Isolate acute cystitis and ABU does not lead to renal damage. Chronic cystitis may give chronic damage of the bladder. APN can give long-term renal complications and must be recognized and treated appropriately.

1.1      URINARY TRACT INFECTION

UTIs are a heterogeneous group of conditions in which there is growth of microorganisms (bacteria, virus or fungi) in the urinary tract. More frequently, UTIs are due to bacteria. Bacterial UTIs are defined by the demonstration of bacteria in the urine. In centrifugated urine the bacteria are measured in colony forming units/millilitre (CFU/mL). Signs of inflammation of the urinary tract (bladder or kidney) are demonstrated by the presence of white blood cells (WBC) in the urine (Hellerstein S, 1982).

1.2      BACTERIURIA

Bacteriuria signifies the presence of bacteria in the urine. It is important to differentiate it from a simply urinary contamination, frequently observed in small children. Growth of 100,000 CFU/mL of one organism in freshly voided urine is the cut-off between contamination (lower) and true bacteriuria (over). Bladder catheterization may reduce the risk of perineal contamination in young children. A bacterial growth of 10,000 CFU/ml is considered the cut-off to define true bacteriuria in a urine sample obtained by catheter (American Academy of Pediatrics. Committee on Quality Improvement. Subcommittee on Urinary Tract Infection, 1999). The best method for obtaining uncontaminated urine in small children is the suprapubic aspiration. With suprapubic aspiration, any growth in collected urine signifies UTI (Hellerstein S, 1982) (Schlager TA, 2001).

1.3 ASYMPTOMATIC BACTERIURIA

From premature infants to school age children, asymptomatic bacteriuria (ABU) occurs almost exclusively in girls. ABU refers to individuals who have a positive urine culture without symptoms of UTI (Davison JM, 1984) (Hansson S, 1989). Conversely, children do not have ABU when they are symptomatic, experiencing day or night incontinence or perineal discomfort, but have true UTI. Since ABU is usually a benign condition and does not cause renal injury, urine cultures must be performed mainly in children with symptoms and not for screening purpose. The diagnosis of ABU is based on at least 3 consecutive urine cultures that demonstrate the same bacterial strain (> 100,000 CFU/mL) in patients with no symptoms of UTI and signs of inflammation in a blood sample (Ragnarsdóttir B, 2007).

1.4 CYSTITIS

Cystitis is an UTI limited to the urethra and bladder observed most commonly in girls older two years. It presents with localising symptoms, such as dysuria, frequency, urgency, cloudy urine and lower abdominal discomfort. It is frequently associated with WBC in the urine and haematuria. Cystitis can be differentiated in acute, hemorrhagic, eosinophilic and interstitial.

Acute cystitis

Acute cystitis is characterized by acute voiding symptoms, with little or no fever. The infection is limited only to the lower urinary tract. In older children, the risk factors are functional and anatomical abnormalities of the urinary tract. Commonly, acute cystitis can be due to bacteria or virus infections.

Acute hemorrhagic cystitis

Acute hemorrhagic cystitis is commonly due to bacterial or viral agents. Acute hemorrhagic cystitis due to E. coli infection leads to gross haematuria that may last 1-9 days (Loghman-Adham M, 1988-1989). Hemorrhagic cystitis attributed to Adenovirus types 7, 11 and 21, is more frequent in males and is self-limiting, with haematuria lasting approximately 4 days (Lee HJ, 1996).

Eosinophilic cystitis

Eosinophilic cystitis is a rare form of cystitis of obscure origin. Only occasionally is found in children. The usual symptoms are haematuria, uretral dilatation with occasional hydronephrosis, and filling defects in the bladder caused by masses that consist histologically of inflammatory infiltrates with eosinophils. Children with eosinophilic cystitis may have had an exposure to an allergen. Peripheral blood eosinophilia or eosinophils in the urine, although helpful diagnostically, are infrequent. Children can show a bladder mass mimicking sarcoma. Bladder biopsy is necessary for diagnostic propose. Biopsy findings are prominent eosinophilic infiltration of the lamina propria and muscularis. Antihistamines and non-steroidal anti-inflammatory drugs, but in some cases intravesical dimethylsulfoxide instillation, is lastly necessary for the treatment (Thompson RH, 2005).

Interstitial cystitis

Interstitial cystitis is a rare disorder characterized by irritative voiding symptoms such as urgency, frequency, and dysuria, and bladder and pelvic pain relieved by voiding with a negative urine culture. The disorder affects adolescent girls and is idiopathic. Diagnosis is made by cystoscopic observation of mucosa ulcers. Treatment includes laser ablation of ulcerated areas. This condition is recognizable and differentiated by dysfunctional voiding secondary to involuntary bladder contractions (Close CE, 1996).

1.5      PYELONEPHRITIS

Many forms of pyelonephritis are recognized.

Acute pyelonephritis

APN refers to infection of the kidneys, and it is the most severe form of UTI in children. APN is characterized by renal parenchyma involvement which fever is the major symptom. Clinically is associated with other symptoms such as malaise, vomiting, abdominal and back pain and tenderness, and poor feeding and irritability in infancy. Diagnosis of APN is made with urine culture, imaging and laboratory markers of inflammation in the blood.

Chronic atrophic pyelonephritis

Chronic pyelonephritis is a persistent kidney inflammation in patients who are predisposed to recurrent APN, such as those with urinary tract obstructions or severe VUR. Sometimes the symptoms may be mild and the inflammatory disease may progress slowly over many years producing kidney failure in the long-term. High blood pressure, anaemia, or symptoms related to renal insufficiency are the result of severe renal involvement. Proteinuria is the worst prognostic feature in patients with pyelonephritic renal scarring.

Pyelonephritic renal scarring

Renal scarring from UTIs refers to the spectrum of radiographic abnormalities in the kidney showed as focal or diffuse areas of parenchymal damage. An acute inflammation of the renal parenchyma may be transient and disappear within 6 months of the infection. Renal scarring may be associated with past or present VUR. The most sensitive scintigraphic technique (Technetium-99m-labeled dimercaptosuccinic acid (DMSA) scan) can visualize acute inflammation as well as a permanent uptake defect in the long-term (Jakobsson B, 1994) (Stokland E, 1996).

Xanthogranulomatous pyelonephritis

Xanthogranulomatous pyelonephritis is a rare form of renal infection characterized by granulomatous inflammation with giant cells and foamy histiocytes. The most common presenting symptoms of xanthogranulomatous pyelonephritis are abdominal pain, fever, weight loss and anorexia. Palpable flank mass is the most common physical examination finding. Xanthogranulomatous pyelonephritis should be included in the differential diagnosis of all children presenting with perirenal or psoas abscess, renal mass and/or non-functioning kidney associated with/or without urolithiasis (Bingöl-Koloğlu M, 2002). Therefore, obstructions and infection with Proteus and E. coli may contribute to the development of this lesion. Finally, xanthogranulomatous pyelonephritis requires total or partial nephrectomy (Korkes F, 2008).

Chapter 2. Epidemiology

Children with UTIs represented nearly 2% of all hospital admissions. UTIs are a common paediatric admission diagnoses: 9th most common in 2000, 10th most common in 2003, and 11th most common in 2006 in USA. Prevalence of UTIs in children varies according with both age and sex, and among ethnic groups.

2.1 Age and sex

Symptomatic urinary tract infection

The overall frequency of UTIs is 1% in boys and 3-8% in girls. Children less than 1 year of age represent 40% of all UTI hospitalizations in the USA. During the 1st year of life, the male/female ratio is 2.8-5.4/1. During the first months of life, there are many boys than girls with UTIs, mostly without high fever. After 6 months of life, girls are prevalent (Riccabona M, 2003). After the age of 1-2 years, there is a sticking female preponderance, with a male/female ratio of 1/10 (Riccabona M, 2003) (Schlger TA, 2001).

The reported rate of recurrent UTIs in children under 5 years of age is 12%, among them the recurrence rate is 34%, with greater risk of recurrence in < 6 months-old infants (Panaretto K, 1999). In an Australian Hospital, among all children with less than 5 year-old, 3.4 % of had serious bacterial UTI (Craig JC, 2010). Population based studies showed that 3-7% of girls and 1-2% of boys had at least one UTI by 6 years of age (Mahant S, 2002). Another study showed that 8.4% of girls and 1.7% of boys developed at least one UTI by the age of 7 years (Hellström A, 1991).

The pooled prevalence rates of febrile UTIs in females aged 0-3 months, 3-6 months, 6-12 months, and >12 months has been 7.5%, 5.7%, 8.3%, and 2.1% respectively. Among febrile males aged less than 3-months, 2.4% of circumcised males and 20.1% of uncircumcised males had a UTI. Among older children with urinary symptoms, the pooled prevalence of febrile and afebrile UTI was 7.8% (Shaikh N, 2008). The average hospitalization for a UTI was 3.1±0.1 days. Average hospitalization did not differ significantly among years, hospital type (general hospital versus paediatric hospital) and age group or gender (Spencer JD, 2010).

Asymptomatic bacteriurias

In at-term infants, the reported prevalence of ABU is less than 1%. In premature infants is 3%. In the first year of life, 0.9% of the girls and 2.5% of the boys had ABU confirmed by suprapubic aspiration (Wettergren B, 1985). In boys, bacteriuria is found almost exclusively during the first 6 months of life. In girls, ABU is found throughout the first year of life (Wettergren B, 1990). Recurrence of bacteriuria is reported in 20% of all children with ABU. The development APN is very rarely observed within 2 weeks from ABU diagnosed by suprapubic aspiration (Wettergren B, 1990).

2.2      Ethnicity

UTI rates are reported higher in white infants (8.0%) than black infants (4.7%) (Shaikh N, 2008). In Sweden, the incidence of UTIs is showed higher during the first year of life. In one-half, the UTIs had been associated with high fever (Hellström A, 1991). In South Africa, bacteriuria is showed in 26% of children aged 0-12 years, and in 17% of children aged 1 week to 8 years. In this setting, UTIs have been reported in association with other conditions including acute respiratory infection, acute diarrhoea and malnutrition (Jeena PM, 1996). In a Nigerian hospital, the reported frequency of UTI has been of 9% among febrile children aged 1-60 months, with a significantly higher prevalence in girls (Musa-Aisien AS, 2003).

Chapter 3.

UROPATHOGENS

The urinary tract infections (UTIs) are a frequent condition seen in paediatric age. The main pathogens involved are bacteria. Therefore, uropathogens viruses are also common, although less frequently associated with severe long-term morbidity. Fungal infection of the urinary tract is seen in patients with immunodeficiency.

3.1      Bacteria

Uncomplicated urinary tract infections

Colonic bacteria are the most frequent urinary pathogens observed during paediatric UTIs. Gram (-) aerobic bacilli are usually of bowel origin, which access to the urinary tract by ascending way via the urethra. Enterobacteriaceae are most commonly isolated from urine samples of children with uncomplicated UTIs (Schlager TA, 2001). Escherichia coli (E. coli) is commonly associated with UTIs in children (Rabasa AI, 2002) (Wammanda RD, 2002) (Musa-Aisien AS, 2003), accounting for 60 to 90% of the UTIs (Schlager TA, 2001) (Riccabona M, 2003). E. coli occurs naturally in the stools (Jantunen ME, 2001), showing a large genetical heterogeneity (Zhang L, 2000). Therefore, genetically identical E. coli species were encountered from the blood, urine and faeces of the same infants with urosepsis suggested that the reservoir of the pyelonephritogenic E. coli is the colon (Jantunen ME, 2001). More than 90% of acute non-obstructive APN by E. coli in children is caused by P fimbriated species that colonized both periurethral areas and stools (Tullus K, 1984). Other common Gram (-) bacteria are Klebsiella, Proteus, Pseudomonas aeruginosa, Aerobacter aerogenes and Staphylococcus saprophyticus. Some authors reported that Proteus is as common as E. coli in males older than 1 year of age in the presence of renal stones. Proteus species are found in 30%