11: Urinary Tract Infection Management

Este capítulo levará aproximadamente 13 minutos para ler.

Por Carolina Acuña M., MD 1, 2, 3
  1. Pediatric Urology, Hospital Padre Hurtado, Las Condes, Chile
  2. Clinica Alemana, Las Condes, Chile
  3. Universidad del Desarrollo, Las Condes, Chile

Introduction

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.

Epidemiology

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.

Clinical Manifestations

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

Age

The prevalence of UTI is higher in boys under 2 years of age and girls under 4 years of age.

Gender

Female patients have a 2 to 4 times higher prevalence of UTI than male patients.

Circumcision

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

Genetics

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.

Vesicoureteral Reflux

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.

Sexual Activity

The association between sexual activity and UTI in women has been demonstrated.

Microbiome

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

Complementary Studies

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.

Indications include:

  • 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.

Voiding Cystourethrography

This is the gold standard for diagnostic confirmation and classification of vesicoureteral reflux.

Indications include:

  • 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.

Treatment

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
  • Dehydration
  • Poor response to adequate antibiotic treatment.
  • Doubtful compliance with antibiotic treatment
  • Urinary tract malformation (single kidney, obstructive uropathy, VUR, etc.)
  • Immunodeficiency
  • 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

Circumcision

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.

Prophylaxis

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

Conclusions

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

Key Points

  • 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.

References

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