Introduction and Definition
Urinary tract infection (UTI) is defined by the presence of organisms in the urinary tract, which is usually sterile. However, since asymptomatic colonisation of the urinary tract can occur, other features such as the presence of inflammatory markers or follow-up cultures may be needed to definitively diagnose a UTI. Clinically important infections usually occur due to bacteria, although viruses, fungi, and parasites can also cause infection.1Zorc JJ, Kiddoo DA, Shaw KN. Diagnosis and Management of Pediatric Urinary Tract Infections. Clinical Microbiology Reviews. 2005; 18(2): 417-422.doi:10.1128/CMR.18.2.417-422.2005. Table 1 gives simplified UTI-related definitions.2Iyengar AA, Capolicchio JP, El-Sherbiny M, et al. Issues related to Pediatric Urology. In: Phadke K, Goodyer P, Bitzan M (eds.) Manual of Pediatric Nephrology. Heidelberg,Germany; 2014.p. 263-304.
Prevalence
The risk of having a UTI before the age of 14 years is approximately 1-3% in boys and 3-10% in girls. The incidence of symptomatic UTI in term neonates is approximately 1% and is 3% in preterm neonates. During the first year of life, the male to female ratio is 3-5:1. Beyond 1-2 years, there is female preponderance with male to female ratio of 1:10.2Iyengar AA, Capolicchio JP, El-Sherbiny M, et al. Issues related to Pediatric Urology. In: Phadke K, Goodyer P, Bitzan M (eds.) Manual of Pediatric Nephrology. Heidelberg,Germany; 2014.p. 263-304. In female infants, UTI occurs in 0.1-0.4% and increases up to 1.4% during preschool age and 0.7-2.3% in school age.3Ashraf M, Ahmed K, Ahmed K, et al. Urinary Tract Infection in Children. British Journal of Medicine & Medical Research. 2014; 4(3): 927-936.
Approximately 0.2% of circumcised and 0.7% of uncircumcised male infants are at risk, which declines to 0.1-0.2% during 1-5 years and 0.04-0.2% in school age. UTI may lead to transient renal damage in 40% and permanent renal scarring in 5% of patients. Studies have shown that asymptomatic bacteriuria occurs in 1% in infants, 3% in preschool children and 1% in school-age children. Screening studies in emergency departments suggest that up to 5% of children under the age of 2 years presenting with fever have UTI. Studies have shown that more than 80% of childhood UTIs are caused by Escherichia coli, 10-15% of UTIs are caused by the other gram-negative organisms like Klebsiella, Enterobacter, Proteus, and Pseudomonas. Staphylococcus aureus is usually considered a contaminant, but it can cause illness.3Ashraf M, Ahmed K, Ahmed K, et al. Urinary Tract Infection in Children. British Journal of Medicine & Medical Research. 2014; 4(3): 927-936.
Pathophysiology
Mutual interaction of both human host and bacterial factors contribute to the occurrence of UTI. Bacterial factors that have been well studied in this condition include adherence, growth factors, and features that allow the bacteria to avoid destruction by the human immune response. In serotypes of E. coli frequently isolated in UTI, bacterial adherence to the uroepithelium is enhanced by adhesins, often fimbriae (pili), which bind to specific receptors of the uroepithelium. The interaction of fimbriae with the mucosal receptor triggers internalisation of the bacterium into the epithelial cell, which leads to apoptosis, hyperinfection and invasion into surrounding epithelial cells or establishment of a bacterial focus for recurrent UTI. The human defense mechanisms involve many components of the immune system, which can vary with genetic background and environmental exposures.3Ashraf M, Ahmed K, Ahmed K, et al. Urinary Tract Infection in Children. British Journal of Medicine & Medical Research. 2014; 4(3): 927-936.
Recurrence rate of UTI varies from 10 to 30% in children and most of these recurrences occur within 12 months of the primary infection.3Ashraf M, Ahmed K, Ahmed K, et al. Urinary Tract Infection in Children. British Journal of Medicine & Medical Research. 2014; 4(3): 927-936.
It is important to divide UTI into lower UTI, localised to the bladder and urethra (cystitis and urethritis) and upper UTI of the ureter, collecting system, and renal parenchyma (pyelonephritis). Ascending bacterial infection of the urinary tract is a complex process that has been associated with bacterial adhesion, virulence, and motility properties of infecting microbes as well as host anatomic, humoral, and genetic factors. The presence of fever, chills, and flank pain has usually been considered clinical evidence of upper tract infection.3Ashraf M, Ahmed K, Ahmed K, et al. Urinary Tract Infection in Children. British Journal of Medicine & Medical Research. 2014; 4(3): 927-936.
Diagnosis
History and physical examination: Clinical signs and symptoms of a UTI depend on the age of the child. Newborns with UTI may present with jaundice, sepsis, failure to thrive, vomiting, or fever. In infants and young children, typical signs and symptoms include fever, strong-smelling urine, haematuria, abdominal or flank pain, and new-onset urinary incontinence. School-aged children may have symptoms similar to adults, including dysuria, frequency, or urgency. Boys are at increased risk of UTI if younger than six months, or if younger than 12 months and uncircumcised. Girls are generally at an increased risk of UTI, particularly if younger than one year. Physical examination findings can be nonspecific but may include suprapubic tenderness or costovertebral angle tenderness.4White B. Diagnosis and Treatment of Urinary Tract Infections in Children. Am Fam Physician. 2011; 83(4): 409-415.
Diagnostic Tests: Dipstick tests for UTI include leukocyte esterase, nitrite, blood, and protein. Leukocyte esterase is the most sensitive single test in children with a suspected UTI. The test for nitrite is more specific but less sensitive. A negative leukocyte esterase result greatly reduces the likelihood of UTI, whereas a positive nitrite result makes it much more likely; however, the converse is not true. Dipstick tests for blood and protein have poor sensitivity and specificity in the detection of UTI and may be misleading. Accuracy of positive findings is as follows (assumes a 10 percent pre-test probability) :4White B. Diagnosis and Treatment of Urinary Tract Infections in Children. Am Fam Physician. 2011; 83(4): 409-415.
- Nitrite: 53 percent sensitivity, 98 percent specificity, 75 percent probability of UTI.
- Bacteria on microscopy: 81 percent sensitivity, 83 percent specificity, 35 percent probability of UTI.
- Leukocytes on microscopy: 73 percent sensitivity, 81 percent specificity, 30 percent probability of UTI.
- Leukocyte esterase: 83 percent sensitivity, 78 percent specificity, 30 percent probability of UTI.
- Leukocyte esterase or nitrite: 93 percent sensitivity, 72 percent specificity, 27 percent probability of UTI.
- Blood: 47 percent sensitivity, 78 percent specificity, 19 percent probability of UTI.
- Protein: 50 percent sensitivity, 76 percent specificity, 19 percent probability of UTI.
All febrile children between 2 and 24 months of age with no obvious cause of infection should be evaluated for UTI, with the exception of circumcised boys older than 12 months. Older children should be evaluated if the clinical presentation points toward a urinary source.4White B. Diagnosis and Treatment of Urinary Tract Infections in Children. Am Fam Physician. 2011; 83(4): 409-415.
Imaging procedures with the highest ratings from the American College of Radiology Appropriateness Criteria for further evaluation of select children with UTIs are renal and bladder ultrasonography, radionuclide cystography or voiding cystourethrography, and renal cortical scan. Renal and bladder ultrasonography is effective for evaluating anatomy, but is unreliable for detecting vesicoureteral reflux. Radionuclide cystography or voiding cystourethrography is effective for screening and grading vesicoureteral reflux, but involves radiation exposure and catheterisation. Although voiding cystourethrography is suggested for either girls or boys, radionuclide cystography is suggested only for girls because voiding cystourethrography is needed for adequate anatomic imaging of the urethra and bladder in boys. A renal cortical scan (also called scintigraphy or DMSA scan) uses technetium and is effective for assessing renal scarring, but requires intravenous injection of radioisotope.4White B. Diagnosis and Treatment of Urinary Tract Infections in Children. Am Fam Physician. 2011; 83(4): 409-415.
Long-term outcome studies have not been performed to determine the best initial imaging study in children diagnosed with UTI. Guidelines based on observational studies and expert opinion recommend that all boys, girls younger than three years, and girls three to seven years of age with a temperature of 101.3℉ (38.5℃) or greater receive cystography and ultrasonography with a first-time UTI. An optional imaging strategy for febrile children with UTI, especially those older than three years, is to first perform ultrasonography and a renal cortical scan. This strategy avoids bladder catheterisation with cystography and minimises radiation exposure if the results of the scan are normal. However, if pyelonephritis or cortical scarring is found on the renal cortical scan, cystography is indicated.4White B. Diagnosis and Treatment of Urinary Tract Infections in Children. Am Fam Physician. 2011; 83(4): 409-415.
Observation without imaging should be considered in girls three years or older with a temperature less than 101.3℉ and in all girls older than seven years. The family should share in the decision to perform imaging with the first UTI or delay imaging until the second UTI, if it occurs.4White B. Diagnosis and Treatment of Urinary Tract Infections in Children. Am Fam Physician. 2011; 83(4): 409-415.
Manifestations
Lower Urinary Tract: Classic non-specific – poor appetite, urgency, irritability, dysuria, lethargy, haematuria, vomiting, incomplete emptying, diarrhoea, incontinence and abdominal distension.
Upper Urinary Tract: Classic Non-specific – fever, poor appetite, flank pain, irritability, dysuria, lethargy, haematuria, vomiting frequency, diarrhoea urgency and abdominal distension.5American Urological Association. Pediatric Urinary Tract Infections. Available from th https://www.auanet.org/education/pediatric-urinary-tract-infections.cfm [Accessed on 7 June 2016].
Pyelonephritis, and to a lesser degree renal abscesses, typically begin as a lower UTI that proceeds to an upper UTI as the infections ascends. However, pyelonephritis and renal abscesses can also result from haematogenous spread of infection (e.g., bacteraemia). Symptoms that occur with upper UTI’s overlap those for cystitis, in part because cystitis is common in both. In upper UTI’s, flank pain and fevers (classically intermittent and >39°) are more pronounced and important.5American Urological Association. Pediatric Urinary Tract Infections. Available from th https://www.auanet.org/education/pediatric-urinary-tract-infections.cfm [Accessed on 7 June 2016].
Acute sequelae of paediatric bacterial UTI include the spread of infection outside the urinary tract, resulting in epididymitis or orchitis in boys, and sepsis. The most common serious sequelae of paediatric UTI is pyelonephritis. Chronic pyelonephritis results from persistent infection after acute pyelonephritis and can result in pyonephrosis, xanthogranulomatous pyelonephritis (XGP), and renal parenchymal scarring with hypertension and renal insufficiency. The accumulation of purulent debris in the renal pelvis and urinary collecting system, known as pyonephrosis, occurs when pyelonephritis is accompanied by urinary tract obstruction.5American Urological Association. Pediatric Urinary Tract Infections. Available from th https://www.auanet.org/education/pediatric-urinary-tract-infections.cfm [Accessed on 7 June 2016].
Pyelonephritogenic scarring with renal parenchymal damage occurs more commonly in children than adults for unclear reasons. Renal scarring from pyelonephritis appears to be influenced by at least 5 factors: Age, treatment, host immunity, intrarenal reflux, and urinary tract pressures. Future hypertension occurs in at least 10–20% of children with pyelonephritogenic scarring. Hypertension in this setting occurs independent of the degree of renal scarring.
Children with recurrent pyelonephritis may also develop progressive renal insufficiency without UTI symptoms. End-stage renal disease from reflux nephropathy (pyelonephritogenic scarring in the setting of vesicoureteral reflux [VUR]) accounts for 7–17% of end-stage renal disease worldwide, and 2% of cases in the U.S.5American Urological Association. Pediatric Urinary Tract Infections. Available from th https://www.auanet.org/education/pediatric-urinary-tract-infections.cfm [Accessed on 7 June 2016].
Paediatric UTI guidelines
National Institute for Health and Care Excellence (NICE) guidelines are mentioned in Tables 2 and 3.
Long-term management
Bowel and Voiding Habits: Dysfunctional voiding syndromes and constipation should be considered in young children and adolescents with UTI. Symptoms include recurrent UTI, constipation, encopresis, and day-time enuresis. Dysfunctional voiding if unrecognised and not managed properly could lead to eflux nephropathy. This later syndrome is associated with renal scars, hypertension, and chronic kidney disease. Children should be encouraged to void frequently and hydrate well. Children should have ready access to clean toilets when required and should not be expected to delay voiding. Prophylactic antibiotics are started for at least 6 months or until proper voiding habits are regained. There have been no trials to support this practice.7Habib S. Highlights for Management of a child with a Urinary Tract Infection. International Journal of Pediatrics. 2012; 1–6. doi: 10.1155/2012/943653.
Surgical treatment of VUR: VUR often undergoes spontaneous resolution. The time from first UTI to resolution of VUR is 6-7 yrs. Comparison of medical and surgical treatment of VUR is hard as different studies use various outcomes. Hodsonet al., reported decreased febrile UTIs as the only benefit of surgical management. There was no difference in renal scars or UTIs in general. Surgical treatment for VUR is reserved for patients with high grade and unilateral reflux, recurrent UTIs despite antibiotic prophylaxis, and noncompliance with antibiotics persistence beyond 9 yrs of age. Endoscopic management involving subureteral or intraureteral injection of bulking agent with dextranomer/hyaluronic acid is suggested as first-line treatment.7Habib S. Highlights for Management of a child with a Urinary Tract Infection. International Journal of Pediatrics. 2012; 1–6. doi: 10.1155/2012/943653.
Long-term Follow-up: Infants and children with uncomplicated UTIs who do not undergo imaging investigations do not require follow up by a subspecialist. Infants and children who have recurrent UTI or abnormal imaging results should be assessed by a paediatric specialist. Assessment of infants and children with renal parenchymal defects should include height, weight, blood pressure, and routine testing for proteinuria. Infants and children with a minor, unilateral renal parenchymal defect do not need long-term follow-up unless they have recurrent UTI or family history or lifestyle risk factors for hypertension.7Habib S. Highlights for Management of a child with a Urinary Tract Infection. International Journal of Pediatrics. 2012; 1–6. doi: 10.1155/2012/943653.
Infants and children who have bilateral renal abnormalities, impaired kidney function, raised blood pressure, and/or proteinuria should receive monitoring and appropriate management by a paediatric nephrologist to slow the progression of chronic kidney disease.7Habib S. Highlights for Management of a child with a Urinary Tract Infection. International Journal of Pediatrics. 2012; 1–6. doi: 10.1155/2012/943653.
Infants and children who are asymptomatic following an episode of UTI should not routinely have their urine retested for infection. Asymptomatic bacteriuria is not an indication for follow-up.7Habib S. Highlights for Management of a child with a Urinary Tract Infection. International Journal of Pediatrics. 2012; 1–6. doi: 10.1155/2012/943653.
Parent Education: Healthcare professionals should ensure that when a child or young person has been identified as having a suspected UTI, they and their parents are given information about the need for treatment, the importance of completing any course of treatment and advice about prevention and possible long-term management. Parents should be made aware of the possibility of a UTI recurring and understand the need to be vigilant and to seek prompt treatment from a healthcare professional for any suspected re-infection. They should be educated about healthy voiding and stooling habits as means of preventing UTIs.7Habib S. Highlights for Management of a child with a Urinary Tract Infection. International Journal of Pediatrics. 2012; 1–6. doi: 10.1155/2012/943653.
Prevention
Cranberry Juice: One of the most considerable barriers to treating children with cranberry juice is its palatability. Most studies report a large number of dropouts or withdrawals over time owing to the bitter taste of cranberry juice.
In a recent double-blind randomised placebo-controlled trial in 7 Finnish hospitals, 255 children treated for UTI were given cranberry juice or placebo for 6 months. The investigators found no differences in timing between first recurrences of UTI (p = 0.32), but UTI incidence per person-year at risk was 0.16 episodes lower in the cranberry group (p = 0.035). The number of days on antibiotic therapy was much lower in children receiving cranberry juice (-6 days per patient-year; p < 0.001). This suggests a potential for cranberry juice to reduce recurrent UTIs in children.8Goldman RD. Cranberry juice for urinary tract infection in children. Canadian Family Physician. 2012; 58: 398-400.
Probiotics: Probiotic strains, including Lactobacillus rhamnosus GR-1, Lactobacillus reuteri B-54 and RC-14, have been shown to be safe and efficacious in an oral formulation or as a vaginal suppository in improving the microbiota profile of the vagina and decreasing the risk of recurrent urinary tract infection (RUTI). Various mechanisms appear to be involved, including modulating antimicrobial and inflammatory defenses, up-regulating protective mucin production and reducing the pressure on pathogens to acquire antibiotic resistance genes. A randomised trial comparing probiotics to antibiotic prophylaxis in children with VUR showed equivalent reduction in the incidence of RUTI and development of new renal scarring.9Dave S. Can Probiotics be used in the Prevention of Recurrent UTI in Paediatric Neurogenic Bladder? Available from https://clinicaltrials.gov/ct2/show/NCT02044965[Accessed on 7th June 2016].
Pharmacological Agents used in Paediatric UTI
The choice of antimicrobial agent used empirically for the treatment of paediatric UTI is dictated by practical as well as clinical considerations. Importantly, geographic variations in bacterial susceptibility and resistance patterns to specific antibiotics should be borne in mind when choosing the agent to use before culture and sensitivity results being available. In addition, prior recent antibacterial use can affect resistance.10Ramlakhan S, Singh V, Stone J, et al. Clinical Options for the Treatment of Urinary Tract Infections in Children. Clinical Medicine Insights: Pediatrics. 2014; 8: 31-37. doi:10.4137/CMPed.S8100.
Penicillins (ampicillin): Ampicillin is a beta-lactam antibiotic that can be given orally or intravenously. Its mode of action is similar to benzylpenicillin, but its amino group side-chain enables it to penetrate the outer membrane of some gram-negative bacteria accounting for its broader spectrum of activity. Ampicillin binds to penicillin-binding proteins in the bacterial cell wall and inhibits cell-wall synthesis. It is bactericidal against gram-positive and some gram-negative organisms including E. coli, Proteus species, and Staphylococcus, but ineffective against Klebsiella and penicillinase-producing organisms. It is rapidly absorbed orally but its bioavailability is only 20-60%. A part of the drug is metabolised by the liver and the rest is eliminated unchanged in the urine.
There is concern over bacterial resistance to ampicillin with increased resistance related to widespread use for other childhood infections. This is demonstrated by increased resistance in children who had used amoxicillin within 30 days of their UTI.10Ramlakhan S, Singh V, Stone J, et al. Clinical Options for the Treatment of Urinary Tract Infections in Children. Clinical Medicine Insights: Pediatrics. 2014; 8: 31-37. doi:10.4137/CMPed.S8100.
Co-amoxiclav (amoxicillin-clavulanate): Co-amoxiclav is a combination of amoxicillin and clavulanic acid. Amoxicillin-Clavulanate is not preferred for uncomplicated UTIs. E. coli from patients with acute uncomplicated UTIs have shown high levels of resistance to amoxicillin-clavulanic acid. In UTIs, it is used orally or intravenously to treat beta-lactamase producing coliforms. The drug is rapidly absorbed orally and is better taken before food. It is eliminated by the kidneys. Co-amoxiclav is contraindicated in children with a known penicillin allergy. Twice daily dosing is now a treatment option with doses of 45-60 mg/kg/day of the amoxicillin component.10Ramlakhan S, Singh V, Stone J, et al. Clinical Options for the Treatment of Urinary Tract Infections in Children. Clinical Medicine Insights: Pediatrics. 2014; 8: 31-37. doi:10.4137/CMPed.S8100.
Cephalosporins: Cephalosporins are used orally (e.g., cephalexin) and intravenously (e.g., cefuroxime) to treat UTIs.They are broad-spectrum, bactericidal antibiotics that contain a beta-lactam ring and have a mode of action similar to that of the penicillins. They are effective against Staphylococcus, Klebsiella, and E. coli and are resistant to the action of most betalactamases. Extended-spectrum beta-lactamase (ESBL)- producing E. coli is an increasingly common antibiotic-resistant strain and makes infections caused by these organisms more difficult to treat. Most ESBL-producing E. coli are resistant to cephalosporins, penicillins, fluoroquinolones, and trimethoprim. Hypersensitivity reactions are the main adverse effect, and there is up to 10% cross-reactivity in patients with an allergy to penicillin.10Ramlakhan S, Singh V, Stone J, et al. Clinical Options for the Treatment of Urinary Tract Infections in Children. Clinical Medicine Insights: Pediatrics. 2014; 8: 31-37. doi:10.4137/CMPed.S8100. Collateral damage, a term describing ecological adverse effects of antimicrobial therapy, such as the selection of drug-resistant organisms and colonisation or infection with multidrug resistant organisms, has been associated with use of broad-spectrum cephalosporins and fluoroquinolones. Broad-spectrum cephalosporins, in particular, have been associated with collateral damage, the most concerning of which is ESBL resistance among gram-negative bacteria.
Fluoroquinolones (ciprofloxacin): Ciprofloxacin is a fluoroquinolone used to treat upper UTIs. It is bactericidal and works by inhibiting DNA-gyrase activity and interfering with DNA replication. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms; however, anaerobes are generally resistant to ciprofloxacin. Ciprofloxacin is well absorbed orally, rapidly and widely distributed into body tissues, and mostly eliminated by the kidneys. In children, the use of ciprofloxacin should be restricted to prove that pyelonephritis is caused by E. coli.10Ramlakhan S, Singh V, Stone J, et al. Clinical Options for the Treatment of Urinary Tract Infections in Children. Clinical Medicine Insights: Pediatrics. 2014; 8: 31-37. doi:10.4137/CMPed.S8100. Of note, Infectious Diseases Society of America (IDSA) guidelines on the treatment of UTIs discourage use of fluoroquinolones for acute, uncomplicated UTI. Experts are concerned about overuse of fluoroquinolones leading to increased prevalence of fluoroquinolone-resistant pathogens that have major implications for the treatment of more serious infections.
Aminoglycosides (gentamicin): Gentamicin is an aminoglycoside antibiotic and an initial intravenous option for children with an upper UTI. It is used intravenously, because oral absorption is negligible. It is bactericidal and works by binding to the bacterial ribosomes interfering with protein synthesis. It is effective against all aerobic gram-negative rods including Pseudomonas and Proteus and is also effective against Staphylococci. All anaerobic organisms are resistant to it. It is eliminated unchanged by glomerular filtration.
The dose of gentamicin is weight related and should be calculated on the child’s ideal weight to avoid excessive dosage. It requires close monitoring and the peak and trough levels should be measured during treatment. The initial once-daily dose is 5-7 mg/kg. Subsequent doses are adjusted according to serum gentamicin concentration. The two major adverse reactions of gentamicin are ototoxicity and nephrotoxicity. Damage to the sensory cells of the ear can lead to hearing loss, balance problems, and tinnitus. Gentamicin damages cells in the proximal tubule, which causes kidney injury because of acute tubular necrosis. Renal function should be measured regularly, and if there is renal impairment, the interval between doses should be increased or the dose should be decreased. It is contraindicated in children with myasthenia gravis.10Ramlakhan S, Singh V, Stone J, et al. Clinical Options for the Treatment of Urinary Tract Infections in Children. Clinical Medicine Insights: Pediatrics. 2014; 8: 31-37. doi:10.4137/CMPed.S8100.
Trimethoprim and Co-trimoxazole: Trimethoprim is a bacteriostatic antibiotic used in the first-line treatment and prophylaxis of uncomplicated UTIs. E. coli, Proteus, Klebsiella, and Enterobacter species are usually sensitive to trimethoprim. It is rapidly absorbed orally, primarily metabolised in the liver, and the remainder is eliminated unchanged by the kidneys.
Trimethoprim and sulfamethoxazole (co-trimoxazole) are commonly used in combination because of their synergistic effects. They are combined in a ratio of 1:5, and oral and intravenous preparations are available. Trimethoprim is a diaminopyrimidine, and sulfamethoxazole is a sulfonamide. Cotrimoxazole inhibits the synthesis of tetrahydrofolic acid, which is required for the synthesis of bacterial amino acids and nucleic acid with the two components of the drug inhibiting different steps in the folate synthesis pathway. It is bactericidal against a broad spectrum of gram-positive and gram-negative aerobic bacteria with activity against some anaerobes. Both components of the drug are well absorbed, and its bioavailability is 100%. Although its use has declined because of the incidence of severe allergic reactions, adverse events, and widespread bacterial resistance comparable to that seen with ampicillin, it is still used in up to 49% of ambulatory UTIs. Trimethoprim on its own is particularly used in UK practice, with high levels of resistance correspondingly seen.
Trimethoprim and co-trimoxazole are contraindicated in folic acid deficiency, severe liver disease, renal failure, pregnancy, neonates, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and acute hepatic porphyria.10Ramlakhan S, Singh V, Stone J, et al. Clinical Options for the Treatment of Urinary Tract Infections in Children. Clinical Medicine Insights: Pediatrics. 2014; 8: 31-37. doi:10.4137/CMPed.S8100. For many years, trimethoprim-sulfamethoxazole was the preferred antibiotic for the treatment of UTI, given its efficacy and low cost. However, development of a high prevalence of trimethoprimsulfamethoxazole resistance among uropathogens has discouraged use of this drug in communities.
Nitrofurantoin: i) It is well absorbed orally and undergoes significant hepatic degradation to inactive metabolites. Because of its extended metabolism and relatively poor tissue penetration, nitrofurantoin is used solely as a urinary tract disinfectant since it will achieve bactericidal concentration only in urine.
ii) Nitrofurantoin is usually effective in treating Staphylococci, Streptococci and most community-acquired gram-negative uropathogens. Despite its widespread use, bacteria rarely develop resistance to nitrofurantoin. This is most probably due to the fact that the drug does not achieve significant levels in intestinal or vaginal tissues and does not alter the normal flora in these areas.11Cendron M. Antibiotic Prophylaxis in the Management of Vesicoureteral Reflux. Advances in Urology. 2008; 1 – 6. Doi:10.1155/2008/825475. This lack of resistance could also be due to its multimodal mode of action. Nitrofurantoin is available as a 50 mg modified preparation for use in children. The dose of nitrofurantoin is 5-7 mg/kg, every 6 hours. In children above 20 kg, nitrofurantoin formulation of modified release (50 mg) should be preferred in BID doses, as it brings adequate urinary concentration throughout 12 hours. Release pattern is approved by USFDA. Modified release offers better GI tolerance.
iii) The clinical advantages of Nitrofurantoin modified release formulation is attenuation of adverse effects, fewer fluctuations in plasma drug concentration, and enhanced patient compliance.12Shah RC. Urinary Tract Infection in Children: A Review. Pedia Flash. 2016; 2(1): 1 – 5.
The clinical trial data provide strong support for consideration of nitrofurantoin as an effective agent for treatment of UTI. Demonstration of efficacy, with minimal drug resistance or propensity for collateral damage, makes nitrofurantoin an attractive agent for lower UTI.
Conclusion
UTI can be caused by various agents such as bacteria, viruses, fungi and parasites. It can be divided into lower UTI (cystitis and urethritis) and upper UTI (pyelonephritis). The diagnosis of paediatric UTI can be divided into 2 parts: History and physical examination & diagnostic tests. There are various aspects in long-term management of paediatric UTI such as bowel and voiding habits; antibiotic prophylaxis; surgical treatment of VUR; long-term follow-up and parent education. The future prospects in preventing paediatric UTI are cranberry juice and probiotics which act against recurrent UTI. Various pharmacological agents are used for treating paediatric UTI; amongst them nitrofurantoin is unique as it is well absorbed orally and bacteria rarely develop resistance to it.
References
- Zorc JJ, Kiddoo DA, Shaw KN. Diagnosis and Management of Pediatric Urinary Tract Infections. Clinical Microbiology Reviews. 2005; 18(2): 417-422.doi:10.1128/CMR.18.2.417-422.2005.
- Iyengar AA, Capolicchio JP, El-Sherbiny M, et al. Issues related to Pediatric Urology. In: Phadke K, Goodyer P, Bitzan M (eds.) Manual of Pediatric Nephrology. Heidelberg,Germany; 2014.p. 263-304.
- Ashraf M, Ahmed K, Ahmed K, et al. Urinary Tract Infection in Children. British Journal of Medicine & Medical Research. 2014; 4(3): 927-936.
- White B. Diagnosis and Treatment of Urinary Tract Infections in Children. Am Fam Physician. 2011; 83(4): 409-415.
- American Urological Association. Pediatric Urinary Tract Infections. Available from th https://www.auanet.org/education/pediatric-urinary-tract-infections.cfm [Accessed on 7 June 2016].
- National Institute for Health and Care Excellence. Urinary Tract Infection in under 16s: diagnosis and management. Available from https://www.guidelines.co.uk/nice/uti-children th [Accessed on 7 June 2016].
- Habib S. Highlights for Management of a child with a Urinary Tract Infection. International Journal of Pediatrics. 2012; 1–6. doi: 10.1155/2012/943653.
- Goldman RD. Cranberry juice for urinary tract infection in children. Canadian Family Physician. 2012; 58: 398-400.
- Dave S. Can Probiotics be used in the Prevention of Recurrent UTI in Paediatric Neurogenic Bladder? Available from https://clinicaltrials.gov/ct2/show/NCT02044965[Accessed on 7th June 2016].
- Ramlakhan S, Singh V, Stone J, et al. Clinical Options for the Treatment of Urinary Tract Infections in Children. Clinical Medicine Insights: Pediatrics. 2014; 8: 31-37. doi:10.4137/CMPed.S8100.
- Cendron M. Antibiotic Prophylaxis in the Management of Vesicoureteral Reflux. Advances in Urology. 2008; 1 – 6. Doi:10.1155/2008/825475.
- Shah RC. Urinary Tract Infection in Children: A Review. Pedia Flash. 2016; 2(1): 1 – 5.