Management of Urinary Tract Infections in Children

Urinary tract infection (UTI) is defined as a significant growth of bacteria in the urine, together with fever, lethargy, dysuria, pain, anorexia, vomiting and possible kidney scarring.1,2,3 UTIs are usually caused by gram-negative aerobic bacilli; approximately 80% are caused by Escherichia coli.2,4 Other causative enterobacteria include Enterobacter, Citrobacter, Proteas, Providencia, Morganella and Serratia.4 Proteus is common in boys and in children with renal stones.5 Coagulase-negative Staphylococci have also been isolated.5 Premature infants can also develop a fungal UTI, usually caused by Candida species.4


Introduction
Urinary tract infection (UTI) is defined as a significant growth of bacteria in the urine, together with fever, lethargy, dysuria, pain, anorexia, vomiting and possible kidney scarring. 1,2,3UTIs are usually caused by gram-negative aerobic bacilli; approximately 80% are caused by Escherichia coli. 2,4Other causative enterobacteria include Enterobacter, Citrobacter, Proteas, Providencia, Morganella and Serratia. 4Proteus is common in boys and in children with renal stones. 5Coagulase-negative Staphylococci have also been isolated. 5Premature infants can also develop a fungal UTI, usually caused by Candida species. 4

Classification of UTIs
Urinary tract infections may be classified as follows: • Asymptomatic bacteriuria: is the absence of clinical signs and symptoms with the presence of bacteriuria.
• Cystitis: localised to the urethra and bladder.Dysuria, frequency, urgency, cloudy urine and lower abdominal discomfort are diagnostic symptoms, while pyuria and haematuria can also occur.This condition is common in girls over two years of age.
• Acute pyelonephritis (AP): presents systemically as high fever, malaise, vomiting, abdominal and loin pain and tenderness, poor feeding and irritability in infants. 6AP is a serious bacterial illness and has a high risk of sepsis and meningitis in young children. 7Uncomplicated UTI: infection is limited to the lower urinary tract and there are no associated urological anomalies.Symptoms include dysuria, frequency, urgency, cloudy urine and abdominal discomfort.Urine dipstick tests are positive for leukocyte esterase, nitrites and haematuria. 8,9Complicated UTI: an infection of the urinary tract involving the renal parenchyma (AP) or which is associated with underlying congenital anomalies of the kidneys or the urinary tract.It may result in significant short-term morbidity, including septic shock and acute renal failure, especially in infants. 8,9Is can be a significant source of morbidity in paediatrics and is a common cause of acute illness. 1,10Congenital genitourinary conditions, immature host defences, female gender, lack of circumcision in boys, and a prior history of UTI, are all risk factors for UTIs in paediatrics. 11According to Alper, 7% of girls and 2% of boys will have a UTI that is culture-confirmed and symptomatic by the age of six. 5 In both sexes, in the first year of life, febrile UTIs show the highest incidence whilst non-febrile UTIs occur predominately in girls older

REVIEW
than three years of age. 12Diagnosing UTI in paediatrics can be a challenge because the clinical presentation may be nonspecific in infants.Invasive methods like urethral catheterization are needed to obtain a reliable urine culture, and for this reason there may be a delay in diagnosis and treatment. 13Boys under the age of one have a higher incidence of UTI; however, UTI prevalence increases in girls after the age of one.Renal scarring is thought to develop after a single UTI in approximately 15-41% of children and chronic kidney disease, proteinuria, hypertension, and complications during pregnancy (if applicable) some few of the long-term problems. 1re than 6 billion dollars in direct healthcare costs are incurred by an estimated 150 million cases of UTI that occur annually worldwide. 14With pyelonephritis, younger age, male gender, higher comorbidity status, and concurrent hydronephrosis, stones or sepsis being the strongest predictors for inpatient admission, early signs and symptoms of UTIs in paediatrics need to be identified and treated aggressively to potentially reduce direct healthcare costs. 11e ages of paediatric patients were categorised according to the paediatric terminology defined by the National Institute of Child Health and Human Development (NICHD) (2015), developed by Eunice Kennedy Shriver in the USA (Table 1).

Pathogenesis
UTIs typically develop when uropathogens that have colonized the periurethral area ascend via the urethra to the bladder.The pathogens can then spread from the bladder to the kidneys (pyelonephritis) or to the blood stream (bacteraemia).Pathogens can also infect the urinary tract through the direct spread via the faecal-perineal-urethral route. 15

Clinical signs
Clinical signs and symptoms depend on the age of the child.

Diagnosis
A urine dipstick test can be done for screening purposes, and if the dipstick test reveals the presence of leucocytes or nitrites, a clean urine sample should be obtained and sent for microscopy, culture and sensitivity testing. 8,9,16r infants and young children the urine sample should be obtained by transurethral catheterisation or suprapubic aspiration.
For older, toilet-trained children, the urine sample can be obtained using the mid-stream clean catch method. 4,8iteria for the diagnosis of a UTI: 8,9 Any culture from the suprapubic urine sample • A culture of >100 colonies/ml urine of a single organism from a catheter specimen • A pure culture of >100 colonies/ml in a midstream clean catch sample • A consistent culture of a pure growth even with low counts.
A renal ultrasound is recommended for all children who have their first culture-confirmed UTI to assess for structural and functional abnormalities of the urinary tract.Abnormalities include vesicoureteric reflux, posterior urethral valves, ectopic ureters, polycystic kidneys and renal dysplasia.Should the ultrasound reveal an abnormality, a micturating cystourethrogram (MCUG) should be done. 4,8,9

Treatment
Treatment should be tailored to the clinical severity, paediatric age, urosepsis suspicion, non-compliance (refusal of fluids, food and/or oral medication) and hydration status (in the case of severe vomiting or diarrhoea).Those with a high risk of serious illness should immediately be referred to a paediatric specialist for optimal care.[19] Antibiotics are used in the acute management of UTIs, as well as for the prevention of recurrent UTIs.It is important to note that nephrotoxic agents should be avoided where possible.Analgesics may be used to ease voiding symptoms.

REVIEW
Recommended oral antibiotics typically includes sulfamethoxazole and trimethoprim, amoxicillin/clavulanate, first and second generation cephalosporins and nitrofurantoin (Table 3).Parental agents used in the treatment of paediatric UTIs include ceftriaxone, cefotaxime, ampicillin, gentamicin and tobramycin (Table 4).A list of principles to ensure appropriate antibiotic use and an algorithm providing guidance for paediatric UTI treatment per UTI classification can be seen in Table 3.

Analgesics
Paracetamol can be used to provide relief from voiding symptoms. 9,15,20The recommended dose of paracetamol is 15 mg/kg 6 hourly.Both the World Health Organization and the National Department of Health recommend against the use of Non-Steroidal Anti-inflammatories (NSAIDs) as an analgesic for children with UTIs. 9,20

Antibiotic prophylaxis
In paediatrics with a single prior UTI, the use of antibiotic prophylaxis is not routinely recommended.In asymptomatic bacteriuria, antibiotic prophylaxis should not be used.Paediatric patients with recurrent UTIs should be thoroughly assessed to rule out any urinary tract abnormalities, where prophylactic antibiotics may be used, based on an individual evaluation.When prescribing prophylactic antibiotics, it is important to consider the ever increasing AMR (antimicrobial resistance) patterns.Local microorganism susceptibility should be taken into consideration when choosing an agent, and preferably a narrow-spectrum antibiotic should be used.8][19] Tables 4 and 5 provides an overview of antibiotics used in the treatment of paediatric UTI.

Principles for appropriate antibiotic use in paediatric UTI care
Only initiate an antibiotic once a urinalysis has been performed and a urine specimen for culture was obtained.
With the alarming increase in AMR, due care should be taken when choosing an agent.
Local antimicrobial susceptibility patterns should be used when deciding on empiric treatment and should cover the most common uropathogens (Escherichia coli, Enterococcus, Proteus, and Klebsiella species).
Reassess antibiotic 48 hours after initiation and modify according to susceptibility results.
Complicated or uncomplicated UTIs should be treated for 7-10 days.
However, short-courses of therapy may be used in adolescent girls with non-toxic UTIs.
If during the use of prophylactic medication a paediatric develops an infection: do not increase dose of current antibiotic, switch to a different agent.
Antibiotic treatment in the case of asymptomatic bacteriuria is not recommended.The following interventions may be applied: • Addressing dysfunctional elimination syndromes and constipation • Improving bowel habits

Preventative measures
The use of vitamin C, cranberry juice, vaccines with uropathogenic strains and/or probiotics is not recommended due to a lack of scientific evidence. 21

Referral
Referral should be considered in the following circumstances 8,9 : • Poor response, despite adequate treatment (persistent positive culture or fever)

Table 1 :
The 2015 classification of paediatric patients according to the National Institute of Child Health and Human Development

Table 2 :
Clinical signs and symptoms of UTI

Table 3 :
Principles of appropriate antibiotic use in paediatric UTI care

Table 5 :
Parenteral antibiotics used in paediatric UTI care

Table 6 :
15,[17][18][19]tibiotic recommendations *Amoxicillin is typically not recommended because of the high incidence of resistant E. coli.***Reducedosages of 1st generation cephalosporin (e.g.cephalexin at 10 mg/kg), until patient reaches 6 weeks of age.SMZ= sulfamethoxazole15,[17][18][19]ConclusionUTI is an uncomfortable and unpleasant condition, which requires immediate attention in paediatrics.Adequate urine tests are necessary to isolate the bacteria, thus narrowing the choice of antibiotic.Appropriate antibiotic and supportive treatment must be considered to ensure a quick recovery and to prevent complications like renal scarring in young children.With antibiotic resistance taking centre stage globally, using the most appropriate antibiotic is essential to obtain the best results without compromising the patients' wellbeing.Prior to choosing an antibiotic, the allergic status, age and renal function must be established.Supportive treatment like paracetamol together with non-pharmacological advice, such as good hygiene and adequate hydration, can reduce the discomfort for the patient.
*Nitrofurantoin should not be used.*