|Year : 2022 | Volume
| Issue : 1 | Page : 19-28
A contemporary overview of urinary tract infection (UTI) in children
Ranjit R Roy, Rummana T Tonny, Nadira Sultana, Abdullah Al Mamun, Tahmina Jesmin
Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka 1000, Bangladesh
|Date of Submission||08-Mar-2022|
|Date of Acceptance||13-Mar-2022|
|Date of Web Publication||31-May-2022|
Prof. Ranjit R Roy
Department of Pediatric Nephrology, Bangabandhu Sheikh Mujib Medical University, Shahbag, Dhaka 1000
Source of Support: None, Conflict of Interest: None
Urinary tract infection (UTI) is the most common and serious bacterial infection in the pediatric age group. It is more prevalent in girls than in boys, except in early infancy. Escherichia coli is responsible for 80–90% of cases of pediatric UTI. The occurrence and severity of this illness are largely mediated by bacterial virulence factors and host defense mechanism. The clinical manifestations of UTI in children are highly heterogeneous, and non-specific collection of urine sample to diagnose the condition accurately is quiet challenging for young pre-continent children. Till date, urine culture is the gold standard for diagnosing UTI. Selection of appropriate antibiotic for the treatment of UTI must be guided by the local guideline and current sensitivity pattern. Ideal imaging protocol and use of antibiotic prophylaxis are still a matter of debate. Current trend is less use of antibiotic prophylaxis due to increasing antibiotic resistance. Prophylaxis cannot alter the long-term consequences, like renal scarring in selected patients. The debate on the indication and duration of antibiotic prophylaxis is still ongoing. So, this review aimed to provide a contemporary overview on the pathogenesis, clinical findings, diagnosis, imaging investigation, treatment, complications, and preventive measures of UTI including chemoprophylaxis in pediatric population. It also highlights the conflicting recommendations of international guidelines, which reveal the necessity of further research to establish the tailored approach of pediatric UTI.
Keywords: Children, clinical and laboratory parameter, renal scar, UTI
|How to cite this article:|
Roy RR, Tonny RT, Sultana N, Mamun AA, Jesmin T. A contemporary overview of urinary tract infection (UTI) in children. Paediatr Nephrol J Bangladesh 2022;7:19-28
|How to cite this URL:|
Roy RR, Tonny RT, Sultana N, Mamun AA, Jesmin T. A contemporary overview of urinary tract infection (UTI) in children. Paediatr Nephrol J Bangladesh [serial online] 2022 [cited 2022 Dec 1];7:19-28. Available from: http://www.pnjb-online.org/text.asp?2022/7/1/19/346341
| Introduction|| |
Urinary tract infection (UTI) is one of the most common bacterial infections in children which accounts for 5–14% of pediatric emergency visits., It can occur in children with normal urinary tracts or can be the first sign of children with congenital anomaly of kidney and urinary tract (CAKUT) in 30% of the cases. So, a single episode of UTI in children may be the sentinel event for an underlying renal abnormality.,, When UTI involves the kidney, the condition is termed as pyelonephritis (PN). If children develop PN recurrently, it may damage the growing kidney by formation of scar that may predispose to hypertension (HTN), chronic kidney disease (CKD), and finally end-stage renal disease. That is why UTI is important for children.,[8-10]
Prompt diagnosis and treatment are essential for the prevention of acute complications as well as renal scarring. However, establishing a suitable approach and identifying children who are at risk of renal damage is not a simple task. The tendency of UTI recurrence, associated morbidity, and problems with collection of a urine sample accurately offer a significant challenge to the clinician, parents, and children as well.,, Extensive research has been done on pediatric UTI regarding renal imaging indication and long-term antibiotic prophylaxis in the last two decades. Till date, the management of UTI in children remains controversial. Diagnosis, treatment, and follow-up of children with UTI are crucial issues for the pediatricians., The purpose of this review is to summarize the current literature and guidelines on pediatric UTI as well as to give a contemporary overview regarding the assessment and management of UTI in children.
| Epidemiology and Risk Factors|| |
Prevalence of UTI in children varies according to age, sex, race, circumcision status of male child, etc. At least one episode of UTI has been experienced by 8% of children between the ages of 1 month and 11 years., After the initial episode, 12–30% of infants and children experience UTI recurrence during the first 6–12 months of their age., It is more common in pre-term than term neonate with a male preponderance., It is more common in boys (3.7%) when compared with girls (2%) in the first year of life. Beyond infancy, the condition is reversed as it is more prevalent in girls. The incidence in girls is 3% and it is 1% in boys during prepubertal age.,, Under 3 months of age, uncircumcised boys had a 20% higher risk of UTI compared with circumcised boys (2.4%).,, In both the groups, the prevalence tends to lower as the age increases. Considering race, the prevalence is two- to four-fold higher in Hispanic and white children than that in the black children.,, Ten percent of white febrile infants and toddlers will have a UTI, whereas 2% of similar black children will have so in the absence of another source of infection.
Additional factors those predispose children to higher risk of developing UTI are high grade vesico-ureteric reflux (VUR), CAKUT, bowel bladder dysfunction (BBD), instrumentation of the urinary tract (particularly indwelling bladder catheterization), kidney stone, sextual activity, diabetes, genetic factors, etc.,,[30-33] Antibiotic therapy may change periurethral flora that may also predispose to UTI.
Risk factors for renal scarring due to acute PN (APN) include high-grade VUR (mostly grades 4 and 5),, fever for more than 3 days before the initiation of antibiotics,,, recurrent UTIs,,[40-42] and organism other than Escherichia coli.,, A genetic predisposition has been found to be associated with recurrent UTI and renal scarring. The genes are HSPA1B gene, ACE I/D gene, toll-like receptor 4 gene, TGFβ gene, etc.,,,,,,
| Etiology|| |
E. coli is responsible for 80–90% of all cases of UTIs in children.,,, Other common uropathogens are Klebsiella, Proteus, Enterococcus, and Enterobacter species.,Proteus infection is more common in uncircumcised boys probably due to its presence under the foreskin. It also predisposed to the formation of phosphate stone by splitting urea to ammonia causing alkalinization of urine and subsequently develops UTI. Organisms such as Pseudomonas, Group B Streptococcus, and Staphylococcus aureus are the causative agents of UTI in children with CAKUT, genitourinary surgery, catheter, and recent antibiotic treatment.,
Hematogenous spread of infection to the urinary tract is common in newborns and children with compromised immune system. Group B Streptococcus, S. aureus, Pseudomonas aeruginosa, Salmonella, and Candida may cause PN through hematogenous route.,,
| Classification System of UTI|| |
1. According to site
UTI involves kidneys (PN) and ureters (ureteritis);
UTI involves bladder (cystitis) and urethra (urethritis).
2. According to severity
when symptoms are mild and children are able to take oral fluid and medications;
when symptoms are more severe such as fever >39°C, persistent vomiting, and dehydration present.
3. According to episode
two or more episodes of UTIs with APN/upper UTI or one episode of UTI with APN plus one or more episodes of UTI with cystitis/lower UTI or three or more episodes of UTI with cystitis;
UTI with the same strain of organism;
UTI with a different strain or species of organism;
UTI occurring in patients receiving antimicrobial prophylaxis.
4. According to symptoms
UTI associated with temperature ≥38°C (100.4 F);
UTI associated with fever and/or urinary symptoms;
Asymptomatic bacteriuria (ABU)
presence of significant bacteria in urine without any symptom of UTI.
5. According to complicating factors
UTI occurs in a patient with normal upper and lower urinary tract, normal renal function, competent immune system, and patients can be managed on outpatient basis.
UTI in newborns, kidney and urinary tract anomaly, urosepsis, organism other than E. coli, atypical clinical course, absence of clinical response to antibiotic within 72 h, renal abscess, abdominal and/or bladder mass, raised serum creatinine.
children with comorbid medical conditions, underlying bladder pathology, indwelling bladder catheter, and atypical clinical course.
| Definitions of Frequently Used Terms in UTI|| |
Urinary tract infection (UTI)
UTI is defined as the invasion and multiplication of microorganisms in significant number within the urinary tract producing symptoms.
Atypical UTI (NICE guidelines)
UTI with one of the followings:
Seriously ill child
Poor urine flow (oliguria not due to dehydration or urinary retention)
Abdominal or bladder mass
Raised serum creatinine level (estimated glomerular filtration rate <80 mL/min/1.73 m2)
Failure to respond to treatment within 48 h
Non-E. coli UTI
UTI without any of these conditions.
A combination of clinical features and positive urinalysis (bacteria, leukocyte esterase, nitrite, and/or ≥5 WBC/HPF) (Guideline, AAP 2011).
A combination of clinical features, positive urinalysis, and a positive urine culture (Guideline, AAP 2011).
Younger kids with non-specific, ill understood, poorly expressed symptoms may be culture-negative and treated with antibiotics for undiagnosed fever.
Bowel bladder dysfunction (BBD)
Spectrum of signs and symptoms include incontinence, constipation and/encopresis associated with functional and behavioral abnormalities of the bowel, lower urinary tract, and pelvic floor.
Renal cortical abnormalities are associated with VUR.
Acquired renal damage is due to APN.
This includes congenital renal cortical abnormalities.
| Pathogenesis|| |
Most UTI results from ascending infection from periurethral colonization of uropathogenic bacteria. They migrate through the urethra to reach the bladder and finally to the kidney in a retrograde fashion.,[61-63] Invasion of the kidney by a pathogenic organism initiates an intense inflammatory response that may lead to renal scarring. The pathogenesis of APN and renal scarring formation is a complex process that is not fully understood.
Virulence factors of pathogen and host defense mechanism: The virulence of uropathogenic strain of E. coli is largely mediated by the presence of P fimbriae (also known as PN-associated pili), lipopolysaccharide (LPS), and hemolysin., Adhesin pap G mediates binding of P. fimbriae to uroepithelium, thereby adhering pathogen to the mucosa. LPS is an endotoxin that contains lipid A in the outer membrane and oligosaccharide core that determines the O-antigen. Lipid A component is responsible for the toxic effects such as fever and acute phase response. Hemolysins produced by uropathogenic strain of E. coli are pore-forming proteins. They increase the cell membrane permeability, thus exerting cytotoxic effect.
LPS binds with toll-like receptor 4 present in the uroepithelium and part of renal tubule. Their activation causes release of proinflammatory cytokines, chemokines, and recruitment of neutrophils and macrophages and generation of reactive oxygen species (ROS)., The proinflammatory responses result in killing of pathogen as well as damaging to the surrounding renal parenchyma. This ultimately causes development of fibrosis and scarring of renal tissue.,,, This process is initiated by macrophages and completed by neutrophils.
| Clinical Manifestation|| |
Clinical presentation of UTI in children is highly heterogeneous, which varies with age. Sometimes, symptoms can be quite obscure that mislead the diagnosis. So, the pediatricians should have a high index of suspicion regarding this common problem of children.
Newborns and infants less than 3 months may have vague and non-specific symptoms, including temperature instability (hyperthermia and fever), lethargy, irritability, apnea, convulsion, diarrhea, vomiting, poor sucking, failure to thrive, prolonged jaundice, malodorous urine, oliguria, or polyuria.,, There is a high probability of bacteremia and sepsis in the age group, and mortality rate is around 10%.,
Approximately 5% of infants less than 12 months with UTI have bacteremia that can lead to urosepsis., The risk of co-existing meningitis and UTI is 1%.
In between 3 months and 2 years of age, unexplained fever is the most common and often the only presenting symptom of UTI.,,, Fever without a localizing sign or obvious source, UTI is a probability. According to the American Academy of Pediatrics (AAP) Guideline, UTI should be considered up to first 2 years of life including the newborn period when patients will come with unexplained fever.
The signs and symptoms are more specific in older children as they are able to verbalize symptoms. A classic study of 200 children demonstrated that fever and abdominal pain were the most common symptoms in 2–5-year-old children. The typical signs and symptoms of UTI were present beyond 5 years of age including fever, dysuria, frequency, urgency, suprapubic on flank pain, incontinence, and renal angle tenderness. Less commonly nocturnal enuresis of recent onset, frank hematuria can also occur. Girls are more commonly present with typical symptoms of cystitis during the adolescent period. They may present with similar symptoms while suffering from sexually transmitted infections or vaginitis.,
Concurrent presence of a weak urinary stream or dribbling of urine suggest neurogenic bladder or posterior urethral valve in boys.
Therefore, a thorough history taking and careful physical examination might be able to prompt diagnosis of UTI in children and thus prevent damage to the kidneys.
| Urine Evaluation|| |
•Urine sample collection
- For pre-continent childrenNon-invasive method: nappy pad, urine bag, clean catch.Invasive method: catheter, suprapubic aspiration (SPA)
- Continent children can void on demand and can provide a mid-stream urine sample. The initial voided urine flushes away the skin flora from urethral orifice. Cleaning the external genitalia carefully with soap and water before taking urine sample further reduces contamination. This opportunistic collection technique is more acceptable for toilet trained children. Another reasonable alternative method of urine collection is the Quick–Wee method. In this method, suprapubic area is stimulated by using a cold water-soaked gauze and then mid-stream urine is collected in a sterile cup.
Contamination is a significant concern for girls and young uncircumcised boys. Girls may benefit from facing backward on the toilet, which splays the legs and labia, thereby reducing contamination from skin and vaginal surface. In case of uncircumcised boys, gentle retraction of prepuce may reduce contamination. UK general practitioners prefer non-invasive collection, whereas USA practitioners prefer catheterization and SPA. Urine sample should be collected before initiation of antibiotic therapy. Treatment should not be delayed in children with sepsis.
There are 3 screening methods of urinalysis:
- Flow imaging analysis technology
The leukocyte esterase test on urine dipstick is a widely available screening test. Most uropathogens but not all (including Klebsiella and Enterococcus) convert nitrates into urinary nitrites. None of them is fully sensitive or specific for UTI. They are considered as a useful screening tool when used in combination. RBC and/or protein on urine dipstick is not specific for UTI, but dipsticks have a good negative predictive value to exclude the diagnosis of UTI.
Sensitivity and specificity of components of urinalysis are summarized in [Table 1]:
Urine culture is the gold standard technique for the diagnosis of UTI. The colony count threshold varies between methods of collection and recommendations of guidelines., While samples are obtained by catheterization, the threshold is 50,000 CFU/mL. For clean catch urine and SPA, it is 100,000(105) and 1000(103) CFU/mL, respectively. According to AAP UTI guidelines 2011, urinalysis positivity and >50,000 CFU/mL of a single uropathogen found in the specimen obtained from bladder catheterization suggest true urine infection. Any growth on SPA constitutes a positive culture, suggested by many guidelines. In febrile children <4 months of age, a cut-off value of 103 CFU/mL can be considered depending on clinical and laboratory findings as well as a correct sampling method.
| Additional Laboratory Studies|| |
Blood culture: Recommended for febrile infants under 3 months of age or fever without a source in a toxic-appearing infant.
Lumber puncture: Recommended for all febrile neonates or ill-appearing infants of <3 months old.
Others: This includes complete blood count, C-reactive protein (CRP), procalcitonin, metabolic panel, electrolyte, renal function tests (blood urea and serum creatinine), ferritin, proinflammatory cytokines, etc.
Test of cure after treatment: These are not routinely recommended and should be done only if clinically indicated.,
| Common Errors in the UTI Diagnosis|| |
Bag urine specimen possesses 80% contamination rate., If bag specimen is sent for culture, a higher threshold such as >100,000 CFU/mL should be considered.
Presence of two or more organisms on urine culture is consistent with contaminations, and non-uropathogens (Lactobacillus, Corynebacterium, Viridans streptococci, coagulase-negative Staphylococci) are considered as contaminants in children.
•Asymptomatic bacteriuria (ABU)
Colonization of pathogen within the bladder in the absence of active inflammation is termed as ABU. It is more common in girls. A recent meta-analysis has been reported a lower prevalence of <0.5%, although its incidence is estimated at 1–3%. It usually resolves spontaneously within few months to few years.,, Antibiotic therapy is not recommended for otherwise healthy individuals with ABU because it may promote antimicrobial resistance and increase the risk of symptomatic UTI.,,, ABU is more frequent in case of children with neurogenic bladder. It has been proposed that urinary biomarkers such as interleukin-6 and neutrophil gelatinase-associated lipocalin may be used to differentiate UTI from ABU. Further research is needed to establish the clinical utility of these emerging tests.
Sterile pyuria is defined as increased WBC count in urine in the absence of bacteria on urine culture. It may occur in partially treated UTI, appendicitis tuberculosis, fungal, viral, or parasite infections, acute glomerulonephritis, systemic lupus erythematosus, Kawasaki disease, foreign body (catheter), kidney stone, interstitial nephritis, analgesic nephropathy, and papillary necrosis.,
•Differentiation of APN from cystitis
Differentiation of APN from cystitis is difficult particularly for pre-verbal children. Sometimes, symptoms are so overlapping that it further makes it difficult to distinct the two conditions. The evidence suggests that children with very high leukocyte count, CRP, or procalcitonin level (>1 µg/mL) in serum are more likely to have APN,,[105-107] although some authors suggest that the utility of these screening tests is limited.
| Imaging|| |
Renal imaging after UTI is needed to identify underlying renal or urinary tract abnormality and to assess the degree of renal injury. Recent guidelines suggest limited role of imaging investigations for children with UTI and these are summarized in [Table 2].
|Table 2: Summary of imaging recommendations from selected international guidelines for young children with UTI|
Click here to view
•Renal ultrasound (US)
Renal bladder ultrasound (US) should be performed in all infants (<2 years) with febrile UTI (AAP 2011) and in older children with recurrent UTIs to exclude any obstruction of the urinary tract. Abnormalities are found in 15% of the cases, and 1–2% of the cases can require drainage. During acute infection, it can mislead the diagnosis of urinary tract abnormalities. E. coli endotoxin may produce dilation, which might falsely reveal hydronephrosis, and edema can change the renal anatomy (size and shape of the kidney) and/or echogenicity of renal parenchyma. So, it can be deferred to 4–6 weeks until after resolution of acute infection depending on clinical situation of the patient. It should be recommended during acute illness if the patient is not responding to treatment (beyond 48–72 h) to diagnose complications such as renal abscess, occult obstruction, stone etc.,,
It is not routinely recommended after first febrile UTI as less than one-third of children with their first UTI have VUR and <10% of them have high-grade VUR (grades 4 and 5)., It should be considered after first UTI in children if abnormality is found in renal bladder US, UTI caused by atypical pathogen, complicated clinical course, known renal scarring.,[113-115] For those who have positive family history of VUR or CAKUT after first febrile UTI, VCUG should be also considered for them.
This is not routinely recommended for all children with UTI. DMSA can detect PN by perfusion defect (reduced uptake) up to 6 weeks of acute phase of a febrile UTI and can also demonstrate renal scars after 3–6 months., In the absence of baseline scan (pre-APN), it is difficult to distinguish acquired from congenital lesions. Cortical defects on DMSA scan may be due to preexisting lesions (congenital) or may be an acute inflammatory reaction associated with APN (acquired). Diffusion weighted magnetic resonance imaging has been shown to diagnose APN accurately and late renal scars as well. So, it can be an alternative to DMSA.
| Complications of UTI|| |
Acute complications include dehydration, electrolyte imbalance, febrile convulsion, renal abscess, complete occlusion of preexisting and partial pelviureteric junction obstruction, urosepsis, and acute kidney injury (AKI). AKI may occur due to dehydration, and nephrotoxic drugs are non-steroidal anti-inflammatory drugs, antibiotics, etc. Long-term complication of APN is renal scarring. The prevalence of renal scarring after febrile UTI is 15% and after the first UTI, it is 3% and after three or more febrile UTIs, it is 29%., Renal scarring subsequently may cause HTN, proteinuria, and CKD.
| Treatment|| |
The choice of empirical antibiotic therapy must be guided by local guidelines and current sensitivity patterns, as it can vary significantly between countries and hospitals. Neonates and young febrile infants (<2 months) are recommended for inpatient parenteral antibiotic therapy because of higher risk of urosepsis and possibility of underlying structural abnormality. AAP recommends that inpatient parenteral therapy should be considered for clinically toxic-appearing children, severely dehydrated children, and those unable to tolerate oral fluid or medications. Failed outpatient therapy, poor adherence to medication, renal or perinephric abscess, immunocompromised children should also consider impatient management. Shifting of intravenous to oral therapy is recommended when there is clinical improvement. Oral antibiotic is to be continued to complete a total course of 14 days. However, majority of pediatric UTIs can be treated effectively in an outpatient basis with oral antibiotic as per culture sensitivity and in vitro response pattern. For uncomplicated febrile UTIs, 7–10 days oral antibiotic therapy is adequate. AAP recommended that all UTI (both cystitis and PN) should be treated for 7–14 days. NICE guideline suggests 7–10 days therapy for PN and 3 days for children >3 months with cystitis. Follow-up should be considered after 48–72 h to assess response to therapy. It has been reported that fever resolves within first 24 h in 68% of children and by 72 h in 92% of the cases. If patient remains febrile beyond 72 h, the clinician should consider suppurative complications as well as resistant or unusual causative organism.In vivo and in vitro antibiotic sensitivity patterns may not be the same always. So, clinical response is more important.
•Role of surgery
In the case of obstructive uropathy, stent or nephrostomy may be required temporarily. Suppurative complications such as renal or perinephric abscess may need surgical or percutaneous drainage. Although surgical treatment is not the first-line therapy for VUR, the chief surgical approach includes ureteric reimplantation (open or laparoscopic), endoscopic subureteral, or intraureteral injection of bulking agents (deflux-dextranomer hyaluronidase).,
| Prevention of UTI|| |
Antimicrobial prophylaxis is commonly used to prevent UTI recurrence in children. The effectiveness of antimicrobial prophylaxis in this regard has been extensively studied. A large multi-center study (RIVUR trial) found that antimicrobial prophylaxis reduced the risk of UTI recurrence by 50% in children with grades I–IV VUR, but the incidence of renal scarring did not differ significantly between the prophylaxis and placebo group (11.9% and 10.2%, respectively). Rather, antibiotic resistance is a major risk of long-term prophylaxis. Another placebo-controlled double-blind (PRIVENT study) trial has reported similar results. Combined results of RIVUR and the Careful Urinary Tract Infection Evaluation (CUTIE) studies found the beneficial effects of prophylaxis in toilet-trained children with VUR and BBD. No study has revealed any beneficial effect of prophylaxis for the prevention of renal scarring. So, limited and selected use of prophylaxis is the current trend. While used, it is to be reviewed every 6 months for assessing the benefits and deciding the continuation or stoppage or any change of prophylaxis needed.
Vitamin A prevents renal scarring in APN and vitamin E ameliorates symptoms of UTI. Treatment of physiological phimosis with local steroid application also reduces incidence of UTI. Intravesical gentamycin instilled in a patient on maintenance CIC also prevents UTI. Role of probiotics in UTI prevention is going to be established.
Cranberry products, mostly available as liquid preparation (juice or syrup), also in tablets or capsule form, have shown some benefits for reducing the risk of UTI in children, although results are conflicting between different studies. The efficiency of probiotics in this context is also uncertain. Vitamin A prevents renal scarring and vitamin E ameliorates the symptoms of UTI.
•Care of prepuce
Daily retraction, cl eaning, and use of topical steroid in the presence of phimosis in boys significantly reduce UTI recurrence. If unsuccessful, circumcision should be considered.,
•BBD (bowel bladder dysfunction)
Febrile and/or recurrent UTI mandate the exclusion of BBD in case of toilet-trained children. Complete bladder emptying using double voiding, prevention or treatment of constipation, and good perineal hygiene are also important to lower the rate of UTI recurrence.
| Conclusion|| |
Accurate diagnosis of pediatric UTI needs a good clinical assessment along with a reliable laboratory result on an uncontaminated specimen of urine. Clinical diagnosis is sometimes misleading and collection procedure is not a simple task for pre-continent children. Prompt diagnosis and initiation of early therapy are mandatory to prevent short-term morbidity such as urosepsis and long-term complications such as renal scarring as well. International guidelines have conflicting recommendations regarding sample collection methods, imaging indications, duration of antibiotic therapy, and efficacy of antibiotic prophylaxis. Despite high prevalence of UTI in the pediatric age group, it has still many unresolved issues. Target research is needed in future to find out the knowledge gap and cost-effective care for UTI in children.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]