11: Urinary Tract Infection Management
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Urinary tract infections are a common problem in children, constituting one of the most frequent infections of bacterial origin in children under 2 years of age. Urinary tract infection (UTI) is defined as the colonization of the urinary tract, from the bladder to the renal parenchyma, by pathogenic microorganisms, frequently bacteria, associated with leukocyturia and variable symptoms, as we will see below.
The incidence of UTI is difficult to estimate because it varies depending on different variables such as age. In the first year of life, it is more common in boys (3.7%), as compared to girls (2%). This incidence starts to shift and in children 2 years and older, females have a two to four-fold higher prevalence of UTI than do circumcised males.1
Prevalence of UTI varies according to age, gender and presence or not of circumcision. The highest prevalence is found in younger infants, girls and uncircumcised boys. Lastly, there is a high rate of UTI recurrence in children (12–30%), especially those with risk factors such as first UTI before 6 months, family history of UTI, dilated vesicoureteral reflux (VUR), and bladder and bowel dysfunction. The goal of early diagnosis and appropriate treatment is to prevent UTI recurrence, promptly diagnose urinary tract malformations, and avoid long-term complications such as arterial hypertension, renal scarring, and impaired renal function.2
Pathogenesis and Etiology
The pathogenesis of UTI results of the interaction between host factors as well as virulent properties of the causative pathogens. A UTI is most commonly due to ascent of bacteria from the perineum into the urinary tract, but hematogenous spread also has a role, particularly on the pathogenesis of pyelonephritis.3 Bacteria can also be introduced iatrogenically with instrumentation of the urinary tract in surgery; or with catheters and stents within the urinary system.
Ascending infection of the urinary tract is a complex process that has been associated with bacterial adhesion, virulence, and motility properties as well as host anatomic, humoral, and genetic factors.4
The etiologic agent that most frequently causes UTI is Escherichia coli, corresponding to 80–90% of cases in children. Other gram-negative uropathogens are Klebsiella, Proteus, Pseudomonas, Enterobacter and Citrobacter spp. Within the gram-positive pathogens we find Staphylococcus epidermidis, Enterococcus species and, with very low frequency, Staphylococcus aureus. Most pathogens originate in the fecal flora ascending to the urethra and bladder from the perineum.5
Classification of Urinary Tract Infections
There are different classification systems according to site, episode, severity, symptoms and complicating factors. The more important concepts are:6,7
Lower urinary tract infection or cystitis which is the infection of the bladder and urethra. The symptoms are usually more classic given the local inflammation of the bladder and these include dysuria, polyakiuria, micturition urgency, hematuria, incontinence and, eventually, hypogastric pain. It is usually more frequent in female patients and those older than 2 years.
Upper urinary tract infection or acute pyelonephritis (APN) corresponds to urinary tract infection that compromises the renal parenchyma, generating inflammation of the renal tissue. Its cardinal symptom is fever greater than or equal to 38º C. The symptoms in younger children are usually non-specific, presenting irritability, vomiting, lethargy, compromised general condition in addition to fever. In older children it is more frequent to find classic urinary symptoms, abdominal pain and low back pain. On some occasions it can present as fever without focus.
Asymptomatic bacteriuria (AB) it is defined as the colonization of the urinary tract by bacteria without generating secondary inflammation. These patients do not present clinical symptoms, their complete urinalysis does not show inflammatory markers, but the urine culture is positive. Most resolve spontaneously and lack clinical significance.
Recurrent UTI is defined as three or more episodes of lower UTI, two or more episodes of APN, or one episode of acute pyelonephritis plus one lower UTI within a year.
Atypical or complicated UTI corresponds to an upper UTI that evolves torpidly. Other elements are usually present that suggest anatomical and functional alterations of the urinary tract. For example, failure to respond to antibiotic treatment at 48 hours, infection by a germ other than E. Coli, sepsis, increased creatininemia, urinary bladder retention, and weak urinary stream. It requires individualized management and study.
The clinical manifestations in UTI are varied and can become very non-specific, particularly in infants and preschoolers. Therefore, in all children with fever without a clear source, it is necessary to consider ruling out a urinary infection.8 Newborns usually debut with urosepsis. The patient is usually severely compromised, lethargic, irritable and refuses to eat. They may or may not have a fever. The symptoms are non-specific, so the clinician's suspicion is tremendously relevant.6 The symptoms in infants are not very different, however, they tend to be less severe, less septic patients. They usually present fever, lethargy, irritability, vomiting and abdominal pain. Only in preschool and older children do urinary symptoms appear such as dysuria, frequency and micturition urgency. They may report abdominal pain and new onset incontinence. When there is involvement of the upper urinary tract, they may report flank pain and tenderness at physical examination. When there is renal parenchyma involvement, they also present fever, a compromised general condition and vomiting. Infants with recurrent UTIs often have poor growth curves and even weight loss.9
When evaluating a patient with suspected urinary infection, predisposing factors for UTI in children should be considered:10
The prevalence of UTI is higher in boys under 2 years of age and girls under 4 years of age.
Female patients have a 2 to 4 times higher prevalence of UTI than male patients.
Febrile uncircumcised male infants have a 4 to 8 times higher prevalence of UTI than circumcised boys. The mucosal surface of the uncircumcised foreskin is more likely to bind uropathogenic bacterial species than keratinized skin on a circumcised penis.11,12
Genetic factors also influence the occurrence of UTI and predispose some children to develop renal scarring after upper urinary tract infection.13
Obstructive Urinary Pathology
Urinary obstructions, whether anatomical, functional or neurogenic, predispose to urinary stasis and favor the development of UTI.
Children with dilated VUR are at high risk of recurrent UTI. There is a close relationship between vesicoureteral reflux, pyelonephritis and renal scars that is under permanent discussion and review. We have transitioned from asserting a very direct cause – effect relationship between reflux, UTI and renal damage to the understanding that VUR remains a risk factor but is not sufficient for the development of renal scars.14
Bladder and Bowel Dysfunction
Up to 40 percent of toilet-trained children with their first UTI and 80 percent of children with recurrent UTI have symptoms of bladder and bowel dysfunction when asked in detail. Bladder and bowel dysfunction is also a risk factor for persistent vesicoureteral reflux, renal scarring and recurrent UTIs.15
Bladder Catheterization and Instrumentation of the Urinary Tract
The risk of UTI increases with a longer duration of bladder catheterization.
The association between sexual activity and UTI in women has been demonstrated.
The microbiome of the urinary tract is being researched as a predisposing factor of UTI. Urobiota helps maintain bladder homeostasis in terms of maintaining the integrity of the urinary tract epithelium, protecting against infections and promoting the proper functioning of the immune system. Alterations of “normal urobiota” has been associated with urological diseases such as urinary tract infections, incontinence, overactive bladder, urolithiasis, and prostate or bladder cancer. This means that dysbiosis has an important role in long term evolution of UTIs.16
Evaluation and Diagnosis
Given the diagnostic suspicion of UTI, a complete urine test and a urine culture should be ordered. Diagnostic confirmation is through a positive urine culture and the number of colony-forming units (CFU) present in the culture. There are non-invasive collection methods such as bag specimen, midstream collection of urine, and invasive methods such as transurethral catheterization and suprapubic bladder aspiration. The bag specimen has a high rate of contamination (more than 70% false positives), which is why when a urine culture is positive, the most appropriate thing is to confirm the diagnosis by taking a new sample. When the result is negative, it allows ruling out UTI. The sampling obtained by midstream collection is recommended in toilet trained children.17,18 In children that are not toilet trained, transurethral catheterization is the recommended method. When this is not possible, the alternative is suprapubic bladder aspiration, ideally under direct ultrasound vision.6 Whatever the method of choice, sampling requires several steps that reduce the risk of contamination. For example, washing the genitals with soap and water without antiseptics. The sample should be examined as soon as possible (fresh urine), if this is not possible it should be kept refrigerated at 2–8˚C for a maximum time of 24 hours.
Considering that the urine culture takes at least 18 hours of incubation, to report bacterial growth, we can support clinical suspicion by observing the chemical and microscopic analysis of the urine sample. The chemical study may show leukocyturia and positive nitrites.19
Microscopic examination is positive (pyuria) when there are more than ≥5 WBC/HPF or ≥10 WBC/mm3 in uncentrifuged urine. UTI is best defined as significant bacteriuria of a clinically relevant uropathogen in a symptomatic patient.6 Pyuria is present in most cases. However, in approximately 10–20 percent of children with UTI, pyuria may be absent.20
Urine culture positivity depends of collection method and number of colony-forming units per milliliter.21
- 50,000 CFU/mL for samples obtained by catheterization
- 100,000 CFU/mL for samples obtained by midstream clean catch
- 1,000 CFU/mL for samples obtained by suprapubic aspiration
In those cases where there is doubt or disagreement between these diagnostic elements, complementary tests such as renal scintigram with dimercaptosuccinic acid (DMSA) or renal doppler ultrasound may help confirm the diagnosis.14
The objective of the imaging study in UTI is to diagnose urinary tract anomalies that may predispose to new urinary tract infections and, therefore, to parenchymal renal damage. Currently, there is no consensus on the images that should be performed in children presenting with a UTI episode. The recommendations are based on expert consensus or on a low level of evidence. In general, it is preferred to perform only the necessary tests, ideally less invasive and with less radiation exposure.
Renal and Bladder Ultrasound
It is used to detect anatomical abnormalities such as dilatation of the collecting system, renal position and size, duplex kidneys, as well as bladder abnormalities. It allows evaluating the renal parenchyma, the presence of renal scars, cortico-medullary differentiation, etc.
In general, renal bladder ultrasound is performed on all patients after the first pyelonephritis, regardless of the patient's age. This is done at 6–8 weeks of the episode.
Indications for early ultrasound, during the UTI episode are those patients with atypical UTI and those under 6 months with recurrent UTI.
Patients with ultrasound alterations, it is recommended to repeat it once a year.
Limitations: It is operator dependent. It depends on the patient's hydration status and has low sensitivity to detect vesicoureteral reflux.14
Dimercaptosuccinic Acid Scintigraphy
This study identifies renal parenchymal defects corresponding to renal scars. In the acute phase of a UTI episode, it can be diagnostic of infection, however, it is not indicated in this phase.
- Atypical UTI in children under 3 years of age.
- Recurrent UTI in any patient regardless of age.
- In patients where renal and bladder ultrasound suggest renal scarring.
Limitations: Limited availability (not all hospitals have Nuclear Medicine units), low doses of radiation, but cumulative.
This is the gold standard for diagnostic confirmation and classification of vesicoureteral reflux.
- UTI in children under 3 years of age with alterations in renal bladder ultrasound such as dilatation of the collecting system, renal scars, bladder alterations or patients with a family history of VUR.
- Recurrent UTI in children under 3 years of age.
- Atypical UTI in children under 6 months.
Limitations: High doses of radiation, it’s an invasive exam and cannot be performed on a patient with UTI, it must be performed with a normal urine test and under antibiotic prophylaxis.
The objectives of UTI treatment are basically three: eradicate the infection, achieve clinical improvement for the patient, and minimize long-term complications, that is, prevent kidney damage. General measures include adequate hydration and management of pain or fever.
Empirical antibiotic treatment should be started while cultures are informed. On patients with uro-prophylaxis it is not recommended to use the same antibiotic used for prophylaxis.
- Lower tract UTI: 1st generation cephalosporin for 3 to 5 days.
- Upper tract UTI: it can be administered orally or parenterally, according to the clinical conditions and the age of the patient.6 Empirical antibiotic treatment alternatives in the case of an outpatient should be 2nd or 3rd generation cephalosporin (oral treatment), amikacin or ceftriaxone may be indicated every 24 hours IV. In hospitalized patients, amikacin can be administered as 1st choice. Alternatives are 2nd or 3rd generation cephalosporin. Treatment should be adjusted according to antibiotic sensitivity, after 24 hours afebrile and according to oral tolerance. If the UTI is associated with bacteremia, intravenous treatment is recommended for at least 5 days.14
Indications for Hospitalization
- Patients under 3 months of age
- Toxic or septic patient
- Poor oral tolerance
- Poor response to adequate antibiotic treatment.
- Doubtful compliance with antibiotic treatment
- Urinary tract malformation (single kidney, obstructive uropathy, VUR, etc.)
- Hydroelectrolytic or renal function alteration.
- In children under 3 months, ampicillin should be associated and in children with impaired renal function, aminoglycosides should not be used. The duration of treatment is 7–10 days.
- Renal abscess: Treatment should last 21 days, initially bi-associated (3rd generation cephalosporin plus an aminoglycoside) and completed with oral antibiotic according to urine culture, after clinical improvement.
Other Key Points of Treatment
This procedure may be recommended in children under 1 year of age with febrile UTI and/or associated urological malformation.
Bladder and Bowel Dysfunction
This group of patients, given the high risk of UTI, have an indication for uroprophylaxis associated with the management of voiding and bowel dysfunction.
The use of antibiotic prophylaxis in healthy children after their first episode of UTI is not recommended. Indication for antibiotic prophylaxis have been limited in time. Common antibiotics used for prophylaxis, when indicated, are shown in Table 1. Nowadays it is indicated in:14
- Children with complex congenital anomalies of the kidney and urinary tract (CAKUT)
- Children with high grade reflux VUR grade IV and V
- Patients with bladder dysfunction such as bladder and bowel dysfunction and lower urinary tract dysfunction (LUTD)22
- Children with 3 or more UTI in a 12-month period. In this group, prophylaxis is indicated for a limited period of time (3 – 6 months)23
Table 1 Common antibiotics and doses used for treatment and prophylaxis of urinary tract infections.
|Antibiotic||Treatment dose||CAP dose||FDA approved indications||Common adverse effects|
|amoxicillin||25–45 mg/kg/day PO divided into 2 doses||15–20 mg/kg daily||any age, UTI treatment||cutaneous / allergic reactions, GI disturbances|
|cephalexin||25–50 mg/kg/day PO divided into 2–4 doses||25 mg/kg daily or divided into 1–2 doses||any age, UTI treatment||cutaneous / allergic reactions, GI disturbances|
|nitrofurantoin||5–7 mg/kg daily divided into 4 doses||1–2 mg/kg daily||> 1 month age, UTI treatment or prophylaxis||hemolytic anemia, GI disturbances, interstitial pneumonitis, cutaneous / allergic reactions|
|trimethoprim||8–10 mg/kg TMP daily divided into 2 doses||2 mg/kg TMP daily||> 12 years age, UTI treatment or prophylaxis||cutaneous /allergic reactions, hematological toxicity|
|Trimethoprim / sulfamethoxazole||8–10 mg/kg TMP daily divided into 2 doses||2 mg/kg TMP daily||> 2 months age, UTI treatment or prophylaxis||cutaneous /allergic reactions, hematological toxicity, hepatotoxicity (kernicterus)|
Suggested Follow Up
Clinicians should be on alert about recurrent symptoms. Up to 30% of children with a UTI may present a reinfection. We have stablished that UTI, especially pyelonephritis is associated to renal scars. So, its relevant to diagnose and treat promptly these infections in order to prevent progression of renal scarring.
Routine surveillance cultures should not be performed in asymptomatic children after their first UTI because they do not improve timely identification of true UTI episodes. Further, treatment of patients who have bacteriuria without symptoms is unproven and may be harmful.24
Therefore, we must train caregivers of young children about the risks of recurrent UTI and advised them to seek medical attention whenever their children present fever and or urinary symptoms.25
Indications for referral to a pediatric nephrologist or urologist:26
- Recurrent UTI
- Patients with CAKUT
- Dilating vesicoureteral reflux
- Impaired kidney function
- Elevated blood pressure
- LUTS and BBD refractory to primary care measures
UTI is a common infection in children. Most UTI are not clinically significant but others, such as pyelonephritis will develop renal scars. These scars, in time, may compromise a children’s renal function. Children at significant risk of chronic renal insufficiency appear to be those with CAKUT, particularly boys with renal dysplasia.
We as caregivers must be watchful of conditions that predispose to repeated urinary infections, taking care of them promptly and appropriately in order to prevent future renal damage. It is also important to identify and manage predisposing conditions such as lower urinary tract dysfunction and vesico ureteric reflux.22
- Urinary tract infections are an important cause of bacterial infections in children.
- The common pathogenic sources are gram-negative organisms. E. coli is responsible for more than 80% of episodes of UTIs.
- The most common risk factors are age, gender, circumcision status, genitourinary abnormalities and genetic factors.
- When facing a patient with a possible UTI always obtain a complete medical history, assess clinical signs and symptoms, perform a thorough physical examination and them ask for laboratory tests.
- Management of a child with UTI is critical due to potential irreversible morbidities which can be avoided with proper treatment.
- The main goal of treatment in the acute period is to cut down clinical signs and control infection avoiding impairment of renal parenchyma.
- Long-term treatment involves preserving renal function by preventing possible renal scarring, preventing recurrent UTIs and correcting underlying urological abnormalities.
- Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of Urinary Tract Infection in Childhood. Pediatr Infect Dis J 2008; 27 (4): 302–308. DOI: 10.1097/inf.0b013e31815e4122.
- Millner R, Becknell B. Urinary Tract Infections. Pediatr Clin North Am 2019; 66 (1): 1–13. DOI: 10.1016/j.pcl.2018.08.002.
- Baraboutis IG, Tsagalou EP, Lepinski JL. et al. Primary Staphylococcus aureus urinary tract infection: the role of undetected hematogenous seeding of the urinary tract. Eur J Clin Microbiol Infect Dis. 2010; 29 (9): 1095–1101. DOI: 10.1007/s10096-010-0967-2.
- Zorc JJ, Kiddoo DA, Shaw KN. Urinary Tract and Genitourinary Suppurative Infections. Pediatric Anaerobic Infections 2005; 8 (2): 375–388. DOI: 10.3109/9780203904022-25.
- AC SES, EA O, RH M. Urinary tract infection in pediatrics: an overview. 1 (Suppl 1): 65–79. DOI: 10.1016/j.jped.2019.10.006..
- Hevia P, Alarcón C, González C, Nazal V, Rosati MP. Management of Urinary Tract Infection in Pediatrics. Textbook of Nephrology 2020; 1 (2): 467–467. DOI: 10.5005/jp/books/12351_39.
- Hoen LA ’t, Bogaert G, Radmayr C, Dogan HS, Nijman RJM, Quaedackers J, et al.. Update of the EAU/ESPU guidelines on urinary tract infections in children. Eur Urol 2021; 79 (4): S446–s448. DOI: 10.1016/s0302-2838(21)00695-3.
- Balighian E, Burke M. Urinary Tract Infections in Children. Arch Dis Child 2018; 58 (5): 399–399. DOI: 10.1136/adc.58.5.399-d.
- Korbel L, Howell M, Spencer JD. The clinical diagnosis and management of urinary tract infections in children and adolescents. Paediatr Int Child Health 2017; 37 (4): 273–279. DOI: 10.1080/20469047.2017.1382046.
- Urinary Tract I S. Reaffirmation of AAP Clinical Practice Guideline: The Diagnosis and Management of the Initial Urinary Tract Infection in Febrile Infants and Young Children 2–24 Months of Age. Pediatric Clinical Practice Guidelines &Amp; Policies, 21st Ed 2016; 138: 501–507. DOI: 10.1542/9781610025034-part01-reaffirmation.
- Singh-Grewal D, Macdessi J, Craig J. Circumcision for the Prevention of Urinary Tract Infection in Boys: A Systematic Review of Randomised Trials and Observational Studies. Yearbook of Urology 2005; 2006 (853): 247–248. DOI: 10.1016/s0084-4071(08)70401-9.
- Hiraoka M, Tsukahara H, Ohshima Y, Mayumi M. Meatus tightly covered by the prepuce is associated with urinary infection. Pediatr Int 2002; 44 (6): 658–662. DOI: 10.1046/j.1442-200x.2002.01633.x.
- Godaly G, Ambite I, Svanborg C. Innate immunity and genetic determinants of urinary tract infection susceptibility. Curr Opin Infect Dis. 2015; 28 (1): 88–96.
- Buettcher M, Trueck J, Niederer-Loher A, Heininger U, Agyeman P, Asner S, et al.. Swiss consensus recommendations on urinary tract infections in children. Eur J Pediatr 2021; 180 (3): 663–674. DOI: 10.1007/s00431-020-03714-4.
- Bulum B, Özçakar ZB, Kavaz A, Hüseynova M, Ekim M, Yalçınkaya F. Lower urinary tract dysfunction is frequently seen in urinary tract infections in children and is often associated with reduced quality of life. Acta Paediatr 2014; 103 (10): e454–e458. DOI: 10.1111/apa.12732.
- Kawalec A, Zwolińska D. Emerging Role of Microbiome in the Prevention of Urinary Tract Infections in Children. Int J Mol Sci 2022; 23 (2): 870. DOI: 10.3390/ijms23020870.
- Veauthier B, Miller MV. Urinary Tract Infections in Infants and Children. Urinary Tract Infections 2020; 02 (5): 69–77. DOI: 10.1128/9781555817404.ch4.
- Okarska-Napierała M, Wasilewska A, Kuchar E. Urinary Tract Infection In Children: Diagnosis, Treatment, Imaging – Critical Comparison Of Current Guidelines. J Pediatr Urol 2017; 13 (6): 10 1016 2017 07 0. DOI: 10.26226/morressier.58fa1769d462b80290b51d08.
- Kanegaye JT, Jacob JM, Malicki D. Automated Urinalysis and Urine Dipstick in the Emergency Evaluation of Young Febrile Children. Pediatrics 2014; 134 (3): 523–529. DOI: 10.1542/peds.2013-4222.
- Roberts KB, Wald ER. The Diagnosis of UTI: Colony Count Criteria Revisited. Pediatrics 2018; 141 (2): 20173239. DOI: 10.1542/peds.2017-3239.
- Mattoo TK, Shaikh N, Nelson CP. Contemporary Management of Urinary Tract Infection in Children. Pediatrics February. 2021; 147 (2): 10 1542 2020–012138. DOI: 10.1542/peds.2020-012138.
- Larkins NG. Hewitt, I.K. Urinary Tract Infection in Children. Curr Pediatr Rep 6. 2018.
- Ammenti A, Cataldi L, Chimenz R, Fanos V, La Manna A, Marra G, et al.. Febrile urinary tract infections in young children: recommendations for the diagnosis, treatment and follow-up. Acta Paediatr 2012; 101 (5): 451–457. DOI: 10.1111/j.1651-2227.2011.02549.x.
- Hoberman A, Wald ER, Hickey RW, Baskin M, Charron M, Majd M, et al.. Oral Versus Initial Intravenous Therapy for Urinary Tract Infections in Young Febrile Children. Pediatrics 1999; 104 (1): 79–86. DOI: 10.1542/peds.104.1.79.
- Shaikh N, Mattoo TK, Keren R. Faculty Opinions recommendation of Early antibiotic treatment for pediatric febrile urinary tract infection and renal scarring. Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature 2016; 170 (848). DOI: 10.3410/f.726584089.793554491.
- National Institute for Health and Care Excellence. Urinary tract infection in children. 2007.
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