Urinary tract Infection - Pediatrics House Staff

Urinary Tract Infections
Lucile Packard Children’s Hospital
Pediatric Residency Training Program
Renal Learning Topics for Residents
Scott Sutherland, MD
CASE PRESENTATION, CLINICAL QUESTIONS, AND BOARDS STYLE QUESTIONS
A 5 month old girl comes to your urgent visit clinic with a two day history of fever and a one day
history of vomiting. She has no diarrhea or URI symptoms but has significantly decreased intake
of both solids and liquids. She has no significant medical history, is currently receiving ibuprofen
for the fever, has no known drug allergies, and has received all scheduled immunizations. She is
an only child who lives at home with her mother and father. There is no significant family history.
On examination, she has the following vital signs: temperature of 102.8°F, heart rate of 145,
respiratory rate 28, oxygen saturation 99%. Her examination is unremarkable and you are unable
to locate a source for her fever.
Question 1: Should this child have urine studies performed?
Answer 1: This child should be evaluated for a urinary tract infection. UTIs are now the most
common occult infection in febrile infants without a source, especially in those who have been
fully immunized. In general, UTIs in infants are accompanied by nonspecific signs/symptoms.
Although in the literature vomiting has not been correlated with the presence of a UTI, in practice,
it is a common nonspecific symptom. Other presenting symptoms include decreased oral intake,
irritability, and in infants less than one month, hyperbilirubinemia. Older children often are able to
localize, and can complain of dysuria, abdominal pain, or flank pain.
There is debate as to which children should be evaluated for UTIs. Suggested approaches range
from fairly simple to quite complex. The AAP “Practice Parameter: The Diagnosis, Treatment,
and Evaluation of the Initial Urinary Tract Infection in Febrile Infants and Young Children”
from 1999 basically suggests that any child under the age of two with an unexplained fever should
be evaluated for a UTI. By comparison, the JAMA article entitled, “Does This Child Have a
Urinary Tract Infection” from 2007, takes an extreme scientific approach by applying likelihood
ratios for each presenting symptom, sign, or demographic characteristic to baseline prevalence
data. This article is fascinating and worth a read if only to see how they move stepwise through a
practice case. However, as interesting as it is academically, it is hard to apply strictly in practice.
It is probably best used to identify some of the more important risk factors for UTIs which can be
used in the clinical setting. Although not absolute, here are some general guidelines for deciding
which febrile children to evaluate for UTIs:
● Pretty much any non-verbal child (2y they probably should have 2 of the following:
-Abdominal pain, dysuria, temp >39C, increased urinary frequency, new
incontinence, vomiting
● If >2 and circumsized, they probably should have 3 or more of the above findings
●Any child with a history of UTI

●Any child with a history of any urologic abnormalities
However, remember: If you find yourself wondering whether or not you should check urine
studies, you probably should.
Question 2: True or False? UTIs are more common in girls.
Answer 2: This is a tough question to answer. Most of the time, the answer would be true.
Between birth and 12 years of age the incidence of UTIs in boys and girls are 1.3% and 3.7%,
respectively. During school age, UTIs are about 3 times more common in girls than in boys and in
adolescence UTIs are far more common in girls than boys. However, under the age of 1, UTIs are
seen more frequently in boys than girls – the ratio is approximately 3-5:1. UTIs are much more
common in uncircumsized boys than circumsized boys.
Question 3: Which urine studies should be obtained?
Answer 3: The diagnosis of a UTI requires both a urinalysis WITH microscopy (microscopic
examination of urine for RBCs, WBCs, and bacteria) and a urine culture. Up to 20% of children
with a UTI will have a normal urinalysis. Additionally, there is a marked false positive rate
associated with urinalysis. A culture is the gold standard for diagnosis and a mandatory test. It
allows you to identify the bacterial pathogen if present, and provides sensitivity data for
antibiotics.
A more complex issue is how to obtain the urine. Truly, a catheterized specimen (or suprapubic
aspirate) is the gold standard technique and any young child who is ill appearing should have urine
obtained by catheterization. Suprapubic aspiration , at least locally, is an uncommonly performed
procedure; additionally it really requires ultrasound guidance. A bagged urine culture is helpful if
it is negative, however, up to 85% of positive cultures from bagged urines are false positives.
Some practice guidelines suggest obtaining a bagged u/a and catheterizing for a culture only if the
u/a looks concerning. This approach is not wholly unreasonable. Older children can have urine
obtained by clean catch midstream collection.
You decide to obtain a urinalysis and culture via urethral catheterization. The urinalysis is
significant for a specific gravity of 1.050, a pH of 6.5, negative blood and protein, 3+ leukocyte
esterase, negative nitrites, 20-30 WBCs per HPF, and 0-5 RBCs per HPF.
Question 4: What do you make of the u/a?
Answer 4: The u/a provides much information, but the most pertinent parameters associated with
UTIs are leukocyte esterase, nitrite, and the presence of pyuria and bacteturia. Some physicians
will wax poetically about the “Gram Stain of an Unspun Urine Sample.” This is truly the best early
detection tool, with a sensitivity and specificity of 93% and 95%, respectively. However, this test
requires technical expertise and is time consuming, and therefore infrequently performed by
laboratories.

The sensitivities and specificities of the tests on the u/a are as follows:
Test Sensitivity Specificity
LE 84% 78%
Nitrite 50% 98%
Both 72% 96%
Pyuria 77% 89%
Bacteria (gram stain) 93% 95% (lower if centrifuged)
Both 85% 99.9%
Based on a meta-analysis (10 studies), in kids less than 5y the UTI likelihood ratios for LE and
nitrites are as follows:
- Negative dip LR 0.2
- Pos LE OR Nitrite LR 6.1
- Pos LE AND Nitrite LR 28
Question 5: What is your preliminary diagnosis?
Answer 5: This child probably has pyelonephritis. The term “UTI” is a general term for an
infection anywhere along the urinary tract. The term “cystitis” suggests localized bladder infection
and the term “pyelonephritis” suggests spread of the infection into the renal parenchyma.
Differentiation between the two diagnoses is important because pyelonephritis is associated with a
risk of renal scarring. In older, verbal children, the diagnosis of pyelonephritis is based on
symptoms such as back pain or severe abdominal pain as well as signs such as costovertebral angle
tenderness. However, in younger children the diagnosis is more challenging and any child with a
febrile UTI should be assumed to have pyelonephritis and managed as such.
Question 6: How should this child be managed? Does she require admission? Can oral
antibiotics be used?
Answer 6: One of the landmark papers on the subject of UTIs is “Oral versus initial intravenous
therapy for urinary tract infections in young febrile children,” which was published in
Pediatrics in 1999. This article demonstrated that it was feasible to treat young children with
febrile UTIs as outpatients using oral antibiotics. They randomized 306 kids between the ages of 1-
24 months to either oral cefixime (3 rd generation cephalosporin) or IV cefotaxime. Oral antibiotics
were equally effective; there was an equivalent time to defervescence, no increase in symptomatic
reinfection, and no increase in renal scarring. While this is an important paper that changed
practice, it is important to realize that it did have limitations. First, they excluded all children with
a previous UTI or urologic abnormality. Second, each child randomized to oral, outpatient therapy
received a witnessed DOUBLE dose of cefixime in the ER. Third, children under the age of 2mo
who were randomized to the oral arm were ADMITTED and given the cefixime under supervision
of hospital staff. Furthermore, children with vomiting were ADMITTED, given IV fluids, and
administered the cefixime under supervision as well. Hmm, are you still sure that you want to

discharge that 3 month old with vomiting and a UTI? The point here is that if you are going to
manage a young child with a febrile UTI as an outpatient, you should make sure the child is low
risk and you need to guarantee exceptional follow up. If you cannot do so, hospitalization is the
safest option. Additionally, if you are going to use oral antibiotics, you should not use keflex. 80-
90% of UTIs are caused by E Coli; nearly 40% of E. Coli recovered from the urine here at LPCH
are resistant to cephalexin. Amoxicillin is an equally poor choice as >50% of E. Coli are resistant
to amoxicillin. Instead you should prescribe an oral 3 rd generation cephalosporin. Your most
common choices are likely to be cefixime (Suprax), cefdinir (Omnicef), or cefpodoxime (Vantin).
The treatment course for pyelonephritis is 14 days. Uncomplicated UTIs in children can be treated
for 10 days.
You should hospitalize children:
● Less than 3-6 months of age (some would argue less than 12 months of age).
● With a clinical concern for bacteremia/urosepsis (ill appearing).
● Who are immunocompromised.
● Who cannot tolerate the oral medication.
● With any degree of renal insufficiency.
● With any urologic abnormality.
An alternative plan that can be used in children managed as outpatients is to administer ceftriaxone
in the ED prior to discharge. The child then follows up with his/her pediatrician or the ED the next
day to get a second dose of ceftriaxone. Then, the child returns again on the 3 rd day when culture
and sensitivity results are available. If the child appears to be improving, you can transition onto
an appropriate oral antibiotic. You need fairly compliant parents for this plan, though.
You diagnose the child with a febrile UTI and suspect she has pyelonephritis. Given the child’s
age and vomiting, as well as your concern regarding follow up, you decide to admit this girl for
parenteral antibiotic therapy. You start the child on ceftriaxone since a dose had already been
administered in the ED. The urine culture grows 55,000 CFU/mL of Escherichia coli 24 hours
after admission.
Question 7: Do you agree with this choice of antibiotics?
Answer 7: Therapy for UTIs, regardless of whether or not the child is admitted, need to be
empiric. Treatment needs to start immediately and it is not reasonable to await culture results. 3 rd
generation cephalosporins are good choices once the child is admitted. If the child is receiving
UTI prophylaxis, has received antibiotics in the past for UTIs, or has urologic abnormalities, you
should at least consider broader spectrum agents. Children who are admitted should receive IV
antibiotics until they have been afebrile for 24-48 hours and can tolerate oral administration of a
comparable antibiotic.
Question 8: Does the culture confirm your original diagnosis?
Answer 8: Yes. Any urine culture obtained by catheterization that grows >10,000 CFU/mL of a
single, true urinary pathogen should be considered positive. Some other centers use a higher cutoff

of 50,000 CFU/mL. If the culture is obtained by a bag or is a clean catch sample, the cutoff is
100,000 CFU/mL. Any growth in a culture obtained by suprapubic aspirate should be considered
positive.
Question 9: Which of the following imaging studies should be obtained in this child?
A. 1 and 2
B. 2 and 4
C. 1, 2, and 4
D. 3 and 5
1. Dimercaptosuccinic acid scan (DMSA)
2. Renal ultrasound
3. Mercaptoacetyltriglycine scan (MAG 3)
4. Voiding cystourethrogram (VCUG)
5. CT scan
Answer 9: The answer is B. Nearly all children with a febrile UTI should have a renal ultrasound
and VCUG performed. For kids older than 3-5 years of age you could make an argument to
postpone the VCUG if the ultrasound is totally normal. However, any child with a recurrent
febrile UTI or any child with a UTI and hypertension, abnormal voiding, renal insufficiency, or a
family history of urologic abnormalities should have both an ultrasound and VCUG performed.
This, like much of the UTI literature, is a controversial topic. It has been made more so by the
debate surrounding the utility of prophylactic antibiotic administration in children with
vesicoureteral reflux.
In general, the goal of imagery is to identify structural abnormalities that might complicate the
child’s care or predispose to recurrent UTIs. The primary abnormalities for which you are
searching are hydronephrosis and vesicoureteral reflux. The aforementioned AAP Practice
Parameter suggests obtaining a renal ultrasound and VCUG in all children less than 2 years of age
with a UTI. In 2003, Hoberman et. al. published a paper entitled, “Imaging studies after a first
febrile urinary tract infection in young children.” It actually used the same patient set as the
paper mentioned above regarding outpatient therapy for UTIs. Remember, they had about 300
children with a first febrile UTI. 88% of the children had completely normal ultrasounds. Per the
manuscript, the remaining 12% had abnormalities that did not change clinical management. They
suggest that the ultrasound is of limited value and recommend that it NOT be performed in
children with a first time UTI if, and this is a really big if, they had prenatal ultrasonography after
30-32 weeks gestation. It is true that prenatal ultrasonography has led to the diagnosis of many
urinary tract abnormalities in utero. However, prenatal ultrasonography is quite operator and
center dependent. Additionally, it is not a dedicated study of the urologic system; they have to
examine every single organ system and not everyone is as fascinated with the kidney as we are. It
just isn’t the same as a post-natal, dedicated renal-bladder ultrasound. Therefore, we recommend
that all children with a first time UTI have a renal ultrasound performed. This study can be
performed at any time and there is no need to delay obtaining it.

We also recommend obtaining a VCUG in the vast majority of infants who have a febrile UTI.
Vesicoureteral reflux is the most common abnormality seen in children with UTIs and because it is
a dynamic condition, the renal ultrasound just doesn’t always detect the hydronephrosis/
pelviectasis that usually accompanies it. However, 30-40% of children with febrile UTIs will end
up having reflux. Kids with more sever reflux (grade III-V) are at greater risk for renal injury;
they are 4-6 times more likely to have injury that children with grade I-II VUR and 8-10 times
more likely than children without reflux.
A DMSA scan is helpful in diagnosing renal scarring, which shows up as a filling defect on the
scan. It can also be used to diagnose pyelonephritis in the acute phase of the illness. However,
because the vast majority of febrile UTIs involve the renal parenchyma, for the most part, we
assume these kids have pyelonephritis and treat them as such. Thus, it is rarely used in this
situation.
A MAG 3 scan is a dynamic scan that provides information regarding both renal perfusion and
excretory function. It doesn’t have a role in the initial evaluation of children with UTIs.
However, it is exceptionally useful for the diagnosis of obstruction. Children who have a U/S that
demonstrates impressive hydronephrosis but have a normal VCUG, will often have a MAG-3 scan
performed to look for UPJ and UVJ obstruction.
There is no need to perform a CT in most cases. However, CTs can identify a renal or perinephric
abscess in children who fail to respond to aggressive IV antibiotic therapy or have recalcitrant
clinical courses.
Upon admission to the hospital a renal ultrasound is obtained. The right kidney is not visualized
and the left kidney, which has undergone compensatory hypertrophy, is noted to have moderate
hydronephrosis. The child defervesces after 48 hours of antibiotic therapy, however, due to the
fact that she has a solitary kidney and the hydronephrosis makes you suspect she has VUR, you
decide to treat her more conservatively. Thus, she receives 7 days of IV ceftriaxone and you
discharge her to complete an additional 7 days of cefixime therapy. You obtain a VCUG after she
completes her antibiotic course and the study reveals grade IV VUR into her solitary left kidney.
Question 10: Should this child be placed on prophylactic antibiotics?
Answer 10: The answer in this case is yes. However, the role of prophylactic antibiotics in the
setting of UTIs and vesicoureteral reflux is a controversial one. The premise for prophylaxis is
that, in the setting of reflux, a small daily dose of an antibiotic will lead to sterilization of the urine;
in theory, reflux of sterile urine will lead to fewer infections and lesser renal scarring than reflux of
urine containing bacteria. However, the benefit of prophylactic administration of antibiotics in the
setting of VUR has been questioned and several smaller studies have suggested that they do not
provide any benefit – namely they do not reduce the incidence of UTI recurrence or renal scarring.
Additionally, most studies have demonstrated that administration of prophylactic antibiotics does
lead to bacterial antibiotic resistance. Unfortunately, most of these studies have been difficult to
apply to clinical practice because they have been small, unblinded, and have excluded patients
with higher grades of VUR. However, the largest study of antibiotic prophylaxis in the setting of
VUR was just published last year. The article was entitled, “Antibiotic Prophylaxis and

Recurrent Urinary Tract Infection in Children.” This study, randomized 576 children with all
grades of VUR (53% had VUR grade III or greater) to either urinary prophylaxis with
trimethoprim-sulfamethoxazole or placebo. They found that use of prophylaxis reduced the
incidence of UTI recurrence from 19% (placebo group) to 13% (treatment group). This represents
a 30% relative reduction, but only a 6% absolute reduction; 14 children would need to be treated
with prophylaxis to prevent 1 recurrent UTI. The data suggested that the benefit of therapy was
greatest during the first 6 months following the initial UTI. This study, like those previous,
suggested that administration of the antibiotic led to bacterial resistance. So what does all this
mean? It means that the decision to use prophylaxis needs to be individualized. Here are some
general rules. Antibiotic prophylaxis should be considered in every patient with a first time febrile
UTI and evidence of VUR. All patients with grade IV and V reflux should receive prophylaxis. I
think all kids with grade III VUR should receive prophylaxis as well. The study demonstrated that
kids with grades I and II VUR did benefit from prophylaxis, however, the risk of scarring in lower
grade VUR (grades I and II) is less than with high grade VUR and the potential benefit may not
outweigh the potential harm. I think that the best approach to kids with grades I and II VUR is to
educate the families about the risks and benefits of VUR and prophylaxis. Make the decision with
them and their concerns in mind. If you decide not to use prophylaxis, it is so, so important to
reinforce with the parents then need to bring their children to medical attention any time they have
a fever without an obvious source; they need to insist that their child have urine studies performed
and if the child has a UTI, he or she needs to be treated promptly. If they have a recurrent UTI,
prophylaxis then needs to be strongly considered regardless of the VUR grade.
Question 11: What antibiotic should be administered for prophylaxis?
Answer 11: For children older than 1-2 months, trimethoprim-sulfamethoxazole or nitrofurantoin
are the best prophylactic options. Cephalexin is not a good choice because it results in high
systemic exposure and resistance. Furthermore, many E. Coli locally are already resistant to it. For
children less than 1-2 months, cephalexin is really your only choice since trimethoprimsulfamethoxazole
and nitrofurantoin are contraindicated younger than this age.
Question 12: When should children with a UTI be referred to a nephrologist?
Answer 12: Referral to a Pediatric Nephrologist or Urologist should be considered in all children
who have recurrent UTIs. A first time UTI doesn’t necessarily require a referral. However,
children, especially young children, with recalcitrant UTIs or UTIs that prove challenging to
manage ought to be referred to a nephrologist. Children who have UTIs and abnormal imaging,
either prenatally or postnatally, should be referred as well. Why should you refer? Well, that is an
excellent question. Some urologic and nephrologic abnormalities require specific management.
For example, high grade reflux may require surgical reimplantion; children with obstructive
uropathy often have decreased urinary concentration ability and require greater than normal fluid
intake and special care to maintain adequate hydration during an illness. Many of these children
can have additional sequelae related to their disease. These include hypertension, salt wasting and
other electrolyte imbalances, proteinuria, and renal insufficiency. The decision whether to refer to
a nephrologist or an urologist will depend a little on the center you are practicing at. Here at
LPCH, we in the nephrology department are always happy to see these children and can certainly
triage those who are better served by urology to their clinic.

The child is placed on prophylaxis with TMP-SMX and remains infection free for the next twelve
months. A repeat VCUG demonstrates that the VUR has fully resolved (30% of grade IV VUR
will resolve on its own). You discontinue the antibiotic prophylaxis and the child lives happily
ever after.
SUGGESTED READING
1. American Academy of Pediatrics. Practice Parameter: The Diagnosis, Treatment, and
Evaluation of the Initial Urinary Tract Infection in Febrile Infants and Young Children.
Pediatrics 2009; 103(4): 843-852.
2. Hoberman, A., Wald, E.R.. Oral Versus Initial Intravenous Therapy for Urinary Tract
Infections in Young Febrile Children. Pediatrics 1999; 104(1): 79-86.
3. Hoberman, A., Charron, M.. Imaging Studies after a First Febrile Urinary Tract Infection in
Young Children. New England Journal of Medicine 2003; 348(3): 195-202.
4. Shaikh, N., Morone, N.E.. Does This Child Have a Urinary Tract Infection? Journal of the
American Medical Association 2007; 298(24): 2895-2904.
5. Craig, J.C., Simpson, J.M.. Antibiotic Prophylaxis and Recurrent UrinaryTract Infection in
Children. New England Journal of Medicine 2009; 361(18): 1748-1759.