12.5 Investigations and Diagnosis

•Older children with pyelonephritis often have tenderness of the flank or costovertebral angle.

•Those with cystitis may have suprapubic tenderness with or without a palpable bladder.

•The finding of hypertension should raise suspicion of hydronephrosis or renal parenchyma disease.

12.5Investigations and Diagnosis

•Complete blood count (CBC)

•Blood cultures (in patients with suspected bacteremia or urosepsis)

•Serum creatinine and blood urea nitrogen

•Serum electrolyte levels

•The diagnosis of a urinary tract infection in children depends on a positive urinary culture.

•Contamination poses a frequent challenge depending on the method of urine collection used.

•A blood culture in febrile infants and older patients who are clinically ill, toxic, or severely febrile.

•Urine analysis:

–Urinalysis alone is not sufficient for diagnosing UTI.

–However, urinalysis can help in identifying febrile children who should receive antibacterial treatment while culture results from a properly collected urine specimen are pending.

–Rapid urine tests (also known as dipsticks or macroscopic urinalysis) remain useful for the diagnosis of UTI.

–Urine dipstick test:

•Urine dipstick testing alone may provide an adequate initial UTI screen.

•Urine dipstick tests for UTI include leukocyte esterase, nitrite, blood, and protein.

•Positive dipstick readings for nitrite, leukocyte esterase, or blood may suggest a UTI.

•Dipstick tests have sensitivities of approximately 85–94 %.

•Dipstick tests for blood and protein have poor sensitivity and specificity in the detection of UTI and may be misleading.

•Automated microscopy has better specificity and likelihood ratios than dipstick testing, but it had slightly lower sensitivity.

–The nitrite test:

•This measures the conversion of dietary nitrate to nitrite by Gram-negative bacteria.

•A positive nitrite test makes UTI very likely.

•The test may be falsely negative if the bladder is emptied frequently or if an organism that does not metabolize nitrate (including all Gram-positive organisms) is the cause of infection.

•The test for nitrite is more specific but less sensitive.

–The leukocyte esterase test:

•This is an indirect measure of pyuria and, therefore, may be falsely negative when leukocytes are present in low concentration.

•Leukocyte esterase is the most sensitive single test in children with a suspected UTI.

•A negative leukocyte esterase result greatly reduces the likelihood of UTI, whereas a positive nitrite result makes it much more likely; the converse is not true, however.

–A microscopic urinalysis:

•This is useful to determine whether there are white blood cells in the urine, which is a sensitive indicator of inflammation associated with infection.

•Microscopic examination of spun urine can evaluate for the presence of white blood cells (WBCs), red blood cells (RBCs), bacteria, casts, and skin contamination (e.g., epithelial cells).

•Approximately 10–20 % of pediatric patients with UTIs have normal urinalysis results.

•Pyuria is 73 % sensitive and 81 % specific for the diagnosis of UTI.

•However, the definition of pyuria is not uniform in the literature.

•The finding of ten white blood cells per microliter in uncentrifuged urine specimen is reported to be a more sensitive indicator of UTI.

•Or, the finding of >5 white blood cells per high-power field in uncentrifuged urine specimen is a more sensitive indicator of UTI.

•The presence of pyuria of at least ten white blood cells per high-power field and bacteriuria are recommended as the criteria for diagnosing UTI with microscopy.

•The absence of pyuria does not exclude a UTI, especially in infants <2 months of age.

•The question is whether infants with positive urine cultures but no pyuria have contamination or asymptomatic bacteruria rather than a UTI.

•Bacteria and yeast seen on microscopic urinalysis are often contaminants.

•The combination of pyuria and bacteruria on urinalysis should raise suspicion for a UTI.

•On a suprapubic aspirate, the presence of five or more WBCs per high-power

field or the presence of ten or more WBC/μL suggests an infection. Gram

stain of unspun urine may reveal organisms.

•A hemacytometer measures cells per volume and has been found to be more sensitive and specific than standard microscopic examination.

•The combination of hemacytometer cell count and Gram stain has been shown in studies to have a sensitivity approaching 95 %.

–A child with a negative urine dipstick for nitrites and leukocyte esterase and no pyuria or bacteruria on microscopic examination has a <1 % chance of having a UTI.

•Urine culture and sensitivity:

–Urine collection must be done before starting antibiotics because a single dose of an effective antibiotic rapidly sterilizes the urine.

–Microscopy and urine culture should be performed in children younger than 3 years instead of dipstick testing.

–The American Academy of Pediatrics (AAP) criteria for the diagnosis of UTI in children 2–24 months are the presence of pyuria and/or bacteriuria on urinalysis and of at least 50,000 colony-forming units (CFU) per mL of a uropathogen from the quantitative culture of a properly collected urine specimen.

–In neonates younger than 2 months of age, the criteria for the diagnosis of UTI include the presence of lower amounts of a single pathogen (10,000–50,000 CFU/mL)

–The use of “urine bags” to collect samples is discouraged due to the high rate of contamination when cultured, and catheterization is preferred in those not toilet trained.

–Urine sample for culture:

•A midstream, clean-catch specimen may be obtained from children who have urinary control.

•Suprapubic aspiration or urethral catheterization should be used in infants or children unable to void on request.

•Suprapubic aspiration is the method of choice for obtaining urine from the following patients:

–Uncircumcised boys with a redundant or tight foreskin

–Girls with tight labial adhesions,

–Children of either sex with clinically significant periurethral irritation

–The diagnosis of UTIs in infants and children is based on colony-forming units (CFU) per mL of an uropathogen depending on the method used to collect the urine sample.

•105 CFU/mL is used for a “clean-catch” mid-stream urine sample

•104 CFU/mL is used for catheterobtained urine specimens

•102 CFU/mL is used for suprapubic urine aspirations

–In young children, urine samples collected with a bag are unreliable compared with samples collected with a catheter. Therefore, in a child who is unable to provide a clean-catch specimen, catheterization should be considered. If urine cannot be cultured within 4 h of collection, the sample should be refrigerated.

–Culture of a urine specimen from a sterile bag attached to the perineal area has a false-positive rate so high that this method of urine collection is not suitable for diagnosing UTI. However, a culture of a urine specimen from a sterile bag that shows no growth is strong evidence that UTI is absent.

–Multiple organisms may be present in patients with structural abnormalities.

•In previously well children who have not been on antibiotics, UTIs are usually due to:

–Escherichia coli

–Klebsiella pneumoniae

–Enterobacter species

–Citrobacter species

–Serratia species

–In adolescent females only, Staphylococcus saprophyticus

•Mixed growth or growth of other organisms usually indicates that the urine is contaminated.

•When children are started on antibiotics for possible UTI, the diagnosis must be reassessed once the results of all investigations are available and antibiotics stopped if UTI appears to be unlikely.

•The American Academy of Pediatrics recommends renal ultrasound and voiding cystourethrogram in all children less than 2 years old who have had a urinary tract infection.

•The National Institute for Health and Care Excellence only recommends routine imaging in those less than 6 months old or who have unusual findings.

•Imaging studies:

–In general imaging studies are not indicated for infants and children with a first

episode of cystitis or for those with a first febrile UTI.

–Imaging should only be performed when it is likely to alter management.

–The choice of imaging should be guided by the safety, cost and accuracy of the procedure to be done.

–Current common imaging options for children with UTI include renal/bladder ultrasound (RBUS), radiographic (e.g., VCUG) and radioisotope (e.g., dimercaptosuccinic acid [DMSA]) techniques.

•Ultrasonography of the urinary tract:

–Ultrasonography is the imaging study of choice in children with UTI.

–Urinary ultrasonography is safe, cheap, noninvasive study, radiation free and easy to perform.

–The AAP Clinical Practice Guidelines recommend routine ultrasonography of the urinary tract after a first febrile UTI in children aged 2–24 months.

–Other indications for ultrasonography of the urinary tract after a febrile UTI in pediatric patients are as follows:

•Delayed or unsatisfactory response to treatment of a first febrile UTI

•An abdominal mass or abnormal voiding (dribbling of urine)

•Recurrence of febrile UTI after a satisfactory response to treatment

•Finally, renal ultrasonography should be considered for any child with a first febrile UTI in whom good follow-up cannot be ensured.

•Voiding Cystourethrography (VCUG):

–Traditionally, VCUG has been recommended for infants and children after a first febrile UTI.

–This is based on assumptions that most upper UTIs occur because of urinary bladder infection and that vesicoureteral reflux (VUR) transfers bacteria in the bladder to the kidney.

–The AAP no longer recommends the routine use of VCUG after the first UTI.

–There is some concern, however, that without VCUG after the first documented

febrile UTI, some cases of significant reflux disease will be missed.

–VCUG is recommended after a second episode of febrile UTI.

–VCUG is indicated if renal and bladder ultrasonography reveals:

•Hydronephrosis

•Renal scarring

•Obstructive uropathy

•Masses or if complex medical conditions are associated with the UTI.

•Other findings suggestive of high-grade VUR

–VCUG should also be performed if a patient has a recurrence of a febrile UTI, even if previous ultrasonographic examination findings were unremarkable.

–Children who respond to treatment for a UTI but afterwards demonstrate an abnormal voiding pattern may need to undergo an evaluation for voiding dysfunction. This evaluation may include standard VCUG.

–In the past, a voiding cystourethrogram (VCUG) was recommended routinely for children between 2 months and 2 years of age who had a febrile UTI, but this is no longer recommended practice.

–A VCUG is the optimal method for diagnosing VUR and for assessing the degree of VUR and the anatomy of the male urethra.

–There are several drawbacks to performing a VCUG including expense, exposure to radiation, and the risk of causing a UTI and discomfort for the child.

–A recent change in practice is that antibiotic prophylaxis is no longer recommended for children with grade I through III VUR because the number needed to receive prophylaxis for 1 year to prevent one UTI is small. Therefore, routine imaging of infants with VCUG after the first UTI is no longer suggested unless abdominal ultrasound is suggestive of renal abnormalities or obstruction, or high-grade VUR. A child with normal kidney structure is not at significant risk of developing chronic kidney disease because of UTIs.

–A VCUG is usually indicated for children <2 years of age with a second welldocumented UTI.

•Where available, a nuclear cystogram (NCG) may be used in place of a VCUG to assess for VUR using radioisotopes.

–NCG delivers less radiation than a VCUG but is less readily available and provides poor anatomical detail for the male urethra.

–NCG can miss posterior urethral valves.

–NCG can be used in place of VCUG as the initial test for VUR investigation in females and in follow-up studies for both sexes.

•A DMSA scan:

–This can be used to diagnose acute pyelonephritis (when performed during acute illness) and to identify renal scars (when performed months following the acute illness).

–DMSA scan is associated with radiation exposure and is not likely to alter management; thus, a DMSA is primarily useful when the diagnosis of acute UTI or of repeated UTIs is in doubt.

12.6Management

•According to AAP guidelines for the treatment of initial UTIs in febrile infants and children aged 2–24 months old, antibiotics can be given orally or parenterally, with the choice of route based on practical considerations.

•Oral antibiotics should not be used in a child who is acutely ill or toxic, has persistent vomiting, or has moderate to severe dehydration. Daily follow-up and good compliance are essential with this approach.

•The AAP recommends basing the choice of antibiotic on local sensitivity patterns if known.

•The choice can be adjusted, if necessary, when results of sensitivity testing become available.

•Antibiotics can be given for 7 or 14 days.

•Amoxicillin has traditionally been a first-line antibiotic for UTI, but increased rates of E.

coli resistance have made it a less acceptable choice.

•Studies have found higher cure rates with trimethoprim/sulfamethoxazole (Bactrim, Septra).

•Other choices include amoxicillin/clavulanate (Augmentin) or cephalosporins, such as cefixime (Suprax), cefpodoxime, cefprozil (Cefzil), or cephalexin (Keflex).

•Patients with a nontoxic appearance may be treated with oral fluids and antibiotics. Toxicappearing patients must be aggressively treated with intravenous (IV) fluids and parenteral antibiotics.

•Most cases of uncomplicated UTI respond readily to outpatient antibiotic treatments without further sequelae.

•Antibiotic resistance among uropathogens is increasing dramatically, however.

•Previous antibiotic exposure (i.e., for otitis media) has been found to be associated with drug-resistant UTIs and should be kept in mind when choosing empiric therapy.

•Children with acute pyelonephritis can be treated effectively with either oral antibiotics or with 2–4 days of IV therapy followed by oral therapy. Oral therapy with a thirdgeneration cephalosporin was as effective as traditional inpatient parenteral treatment.

Antibiotics used for oral treatment of a urinary tract infection

Antibiotics used for oral treatment of a urinary tract infection

lowed by oral antibiotics (10 days) with respect to duration of fever or subsequent renal damage.

•Similarly, no significant differences were found comparing IV antibiotics (3–4 days) followed by oral antibiotics, versus IV antibiotics alone for 7–14 days.

•Most experts recommend initial treatment with oral antibiotics for febrile UTIs in nontoxic children with no known structural urological abnormality, assuming that they are likely to receive and tolerate every dose.

•Data on oral therapy is limited for infants 2–3 months of age, so close follow-up is warranted for this age group. Some experts recommend initial IV antibiotics for this age group.

•While waiting for antibiotic susceptibility results for the likely bacterial pathogen, clinicians should make an empirical choice of antibiotics based on local susceptibility patterns. Aminoglycoside levels and renal function need to be monitored when the aminoglycoside is continued for >48 h.

•If clinical findings indicate that immediate antibiotic therapy is indicated, a urine specimen for urinalysis and culture should be obtained before treatment is started.

•Common choices for empiric oral treatment are:

– A secondor third-generation cephalosporin

–Amoxicillin/clavulanate, or sulfamethoxazoletrimethoprim (SMZ-TMP).

•Patients with a nontoxic appearance may be treated with oral fluids and antibiotics.

•Hospitalization is necessary for the following patients with UTI:

–Patients who are toxemic or septic

–Patients with signs of urinary obstruction or significant underlying disease

–Patients who are unable to tolerate adequate oral fluids or medications

–Infants younger than 2 months with febrile UTI (presumed pyelonephritis)

–All infants younger than 1 month with suspected UTI, even if not febrile

•Antibiotics suggested for parenteral treatment are as follows:

–Ceftriaxone

–Cefotaxime

–Ampicillin

–Gentamicin

•Infants and children with febrile UTI should be treated with antibiotics for 7–10 days.

•Oral antibiotics can be administered as initial treatment when the child has no other indication for admission to hospital and is considered likely to receive and tolerate every dose.

•There is no evidence that children with UTIs and documented bacteremia who have a rapid clinical response to antibiotics require intravenous antibiotics or a longer course of antibiotics.

•The choice of antibiotics should be guided by the resistance pattern of common urinary pathogens in the community and changed to a less broad spectrum agent, if practical, when the sensitivity of the pathogen is known.

•Consider circumcision of male neonates to prevent UTIs.

•A systematic review concluded that routine circumcision in boys does not reduce the risk of UTI enough to justify the risk of surgical complications.

•The AAP policy statement on circumcision is that “the health benefits of newborn male circumcision outweigh the risks and that the procedure’s benefits justify access to this

procedure for families who choose it.” The AAP notes that the benefits of the procedure include prevention of UTIs.

•Children with acute pyelonephritis can be treated effectively with oral antibiotics (e.g., amoxicillin/clavulanate, cefixime, ceftibuten [Cedax]) for 10–14 days or with short-courses (2–4 days) of intravenous therapy followed by oral therapy for a total of 10–14 days.

•Follow-up assessment to confirm an appropriate clinical response should be performed 48–72 h after initiating antimicrobial therapy in all children with UTI.

•Culture and susceptibility results may indicate that a change of antibiotic is necessary.

•If expected clinical improvement does not occur, consider further evaluation.

•Infants <8 weeks old:

–The diagnosis in infants <8 weeks old with a febrile UTI is usually based on fever and on positive results from a urine specimen obtained by catheterization.

–In this age 10,000 colonies/mm3 defines bacteriuria.

–Infants with such findings are usually hospitalized and receive parenteral antibiotic therapy.

–However, clinical judgment may indicate that home treatment is appropriate.

–Parenteral antibiotics may be used with daily follow-up until the patient is afebrile for 24 h.

–Complete 10–14 days of therapy with an oral antibiotic that is active against the infecting bacteria.

•Children with cystitis:

–Children with cystitis usually do not require special medical care other than appropriate antibiotic therapy and symptomatic treatment if voiding symptoms are marked.

–Antibiotic therapy is started on the basis of clinical history and urinalysis results before the diagnosis is documented.

–A 4-day course of an oral antibiotic agent is recommended for the treatment of cystitis.

–Nitrofurantoin can be given for 7 days or for 3 days after obtaining sterile urine.

–A 2- to 4-day course of oral antibiotics appears to be as effective as a 7- to 14-day course in children with lower UTIs.

–Guidelines from the American Academy of Pediatrics recommend limiting fluoroquinolone therapy to patients with UTIs caused by Pseudomonas aeruginosa or other multi- drug-resistant, gram-negative bacteria. Ciprofloxacin (Cipro) is used for complicated UTIs and pyelonephritis attributable to E. coli in patients 1–17 years of age.

–If the clinical response is not satisfactory after 2–3 days, alter therapy on the basis of antibiotic susceptibility

–Symptomatic relief for dysuria consists of increasing fluid intake (to enhance urine dilution and output), acetaminophen, and nonsteroidal anti-inflammatory drugs (NSAIDs)

–If voiding symptoms are severe and persistent, add phenazopyridine hydrochloride (Pyridium) for a maximum of 48 h

•Children with Complicated Pyelonephritis:

•Pyelonephritis is considered complicated when it occurs in:

–A neonate or an infant

–A patient with an anatomic abnormality of the urinary tract or abnormal renal function

–A patient who is immunocompromised

•Start IV fluids, usually at 1–1.5 times the usual maintenance rate.

•Parenteral treatment with a thirdgeneration cephalosporin (e.g., ceftriaxone, cefotaxime) is appropriate initial empiric coverage for a complicated UTI and pyelonephritis to cover for ampicillin-resistant, gram-negative pathogens.

•Add ampicillin if gram-positive cocci are present in the urinary sediment or if no organisms are observed.

•Gentamicin is an alternative empiric choice and may be considered in patients with cephalosporin allergy.

•Monitor renal function and blood aminoglycoside levels if gentamycin is required for more than 48 h.

•The results of urine culture and sensitivity studies are usually available within 48 h.

–If the pathogen is sensitive to the antibiotic used and the child is improving, continue treatment via the parenteral route until the child has been afebrile for 24–36 h, has improved clinically, and is able to retain oral medications.

–An oral antibiotic that is effective against the infecting organism may then be substituted for parenteral therapy.

–The hospitalized patient who is responding to treatment can go home after 48–72 h.

–Continue oral antibiotics for a total of 10–14 days.

•Antibiotic prophylaxis is no longer recommended for grades I through III VUR or pending results of the renal and urinary bladder ultrasound.

•Antibiotic prophylaxis is more often recommended for children with high-grade reflux (grade 3–5).

•The current AAP guidelines do not recommend prophylactic antibiotics to prevent UTI recurrences.

Antibiotics used for parenteral treatment of a urinary tract infection