Urinary Tract Infections in Children:
a Changing Paradigm
R Bhimma
Department of Paediatrics and Child Health
Nelson R Mandela School of Medicine
University of KwaZulu-Natal
Introduction
 UTIs most common serious bacterial infection in childhood.
 UTI occurs in 1.6% of boys and 7.8% of girls.
 1st 3 months of life: more common in boys (3.7% vs 2.0%).
 Higher incidence in older children presenting with BBD.
 Febrile UTIs in children, with or without VUR
HPT and CKD.
renal scarring
 Early guidelines advocated aggressive treatment and
extensive imaging to detect VUR and kidney scarring.
Renal Scarring
Normal kidney
Scarred kidney
Introduction
In the last decade there is a more targeted approach to
UTIs
More judicious use of resources
Harmful procedures and interventions
are avoided
Concerns
 Unnecessary exposure to radiation.

Invasiveness of some procedures

Higher risk of infusion
Oral antibiotics as effective as intravenous antibiotics.
No differences: time to recovery
rates of kidney scarring.
Hoberman A etal Paediatrics 104:79-86, 1999,
Montini G BMJ 335:386,2007,
Hewitt IK etal Ital J Pediatr 37: 57, 2011
Diagnosis of UTI

Varies according to:
 method of urine collection
 number of bacterial species
 clinical presentation.

Culture negative urine:
 prior antibiotic Rx
 complete UT obstruction
 infected cyst
Pediatr Res, 2015 Jul; 78(1):48-55.doi:10.1038/pr.2015.59.Epub 2015 Mar 19.
Plasma neutrophil gelatinase-associated lipocalin predicts acute
pyelonephritis in children with urinary tract infections.
Sim JH, Yim HE, Choi BM, Yoo KH
BACKGROUND:
The identification of acute pyelonephritis (APN) is still a challenge.
RESULTS:
A total of 123 patients were enrolled (53 APN and 70 lower UTI). NGAL levels
were higher in the APN group than in the lower UTI group (233 (129-496) ng/ml
vs. (50.8-110) ng/ml, P< 0.001).
CONCLUSION:
Plasma NGAL can be a sensitive predictor for identifying APN and monitoring
the treatment response of pediatric UTI.
Occult UTI

Fastidious and anaerobic bacteria may not be detected using
standard culture.

Molecular approach 16s DNA PCR, denaturing HPLC, sequencing and
bioinformatic analysis.

Recommended when have leukocyte esterase positive and culture
negative specimens.
Imirzaliogln C. Andrologia 40: 66-71 (2008)
Diagnosis of UTI – dipsticks and microscopy
Post-test probability of UTI with varying baseline risk of UTI for the common near patient tests
Children with fever (5% baseline risk)
Children who have had one
Previous UTI (20% baseline risk)
Positive
Positive
Negative
Post test probability of UTI
Negative
Post test Probability of UTI
Dipstick
Leucocyte esterase
alone
24
2
72
9
Nitrite alone
56
3
91
18
54
3
90
19
18
1
64
6
Microscopy
White cell count
22
2
69
11
Bacteria
37
1
82
5
Gram stained
bacteria
55
0.3
90
19
Leucocyte esterase
and nitrite
Leucocyte esterase
or nitrite
Microbiological threshold for the diagnosis of UTI
Collection method
Colony forming
units
per litre
Number of
bacterial species
Definite UTI
Voided samples
Bag collection
Midstream catch
≥10⁸
1
Catheter samples
≥ 10⁷
1
Any number
1
Suprapubic bladder
aspirate
Williams G et al. J Paediatr Child Health (2012), 48:296-301
Microbiological threshold for the diagnosis of UTI
Collection method
Colony forming units
per litre
Number of
bacterial species
Probable UTI
Voided samples
Bag collection
≥10⁷
1
Midstream catch
≥10⁸
1
Clean catch
≥10⁶
1
≥10⁷
2
Any number
2
Catheter sample
Suprapubic bladder
aspiration
Williams G et al. J Paediatr Child Health (2012), 48:296-301
Classification of UTI
Asymptomatic
bacteraemia
Is defined as a growth of a significant number of an isolated organism
[usually >100,000 colony-forming units (CFU/ml) from urine culture
found in children without symptoms with no pyuria. This should
not be treated as the inappropriate use of antibiotics may promote
antibiotic resistance leading to symptomatic disease and does not
confer any long-term benefit
Classification of UTI cont…
Cystitis
Is defined as infection limited to the urethra and bladder;
symptoms include frequency, urgency, dysuria, lower abdominal
discomfort or pain and or cloudy urine.
Acute
pyelonephritis
Is defined as the presence of high ≥ 38.5°C and/or systemic
involvement, except in some very young infants
Classification of UTI cont…
Simple UTI
Denotes features of lower urinary tract involvement. These children
have only mild pyrexia, but are able to take fluids and oral medication.
They are only slightly or not dehydrated and generally have good
compliance with medication.
Severe UTI
Is defined as the presence of fever of ≥ 39°C, the feeling being ill,
persistent vomiting, and moderate or severe dehydration. When a
child with a simple UTI has a low level of compliance, such a child
should be managed as one with a severe UTI
Classification of UTI cont…
Uncomplicated
UTI
Is defined as the invasion of a structurally and functionally normal
urinary tract by a non-resident infectious organism.
Complicated UTI
Refers to the occurrence of infection in patients with an abnormal
structural or functional urinary tract, or both, that involves the
upper urinary tract and thus manifests as pyelonephritis.
Recurrent UTI
Is defined as the following: ≥ 2 episodes of UTI with acute
pyelonephritis plus one episode of UTI with acute pyelonephritis
plus one or more episodes of UTI with cystitis or lower UTI or three
or more episodes of UTI with cystitis or lower UTI.
Classification of UTI cont…
Atypical UTIs
Are defined as those that fail to respond after 48 hours of appropriate antibiotic
treatment, have poor urine flow, abnormal kidney function, bladder or abdominal
mass, infection by an organism other than E.coli and onset of septicaemia.
Relapsing UTI
Is defined as a prompt recurrent infection with the same organism that occurs
following treatment and implies there has been failure to eradicate the infection
Acute lobar
nephronia
(acute
lobar nephritis)
Is defined as a renal mass caused by focal infection with liquefaction and may lead
to the development of a renal abscess later on.
Pathogenesis of UTI
 Colonisation of distal urethral and peri-urethral area from GIT tract
competitively inhibits colonisation by potential pathogenic bacteria.
 Assent of pathogenic bacteria into UT occurs if there is colonisation by
pathogenic bacteria.
 Systemic spread of infection to kidneys uncommon except in
uncompromised patients.
Pathogenesis of UTI cont..
 Enhanced by the following factors:

Use of broad spectrum antibiotics

Soiling around perineum

Catheters

Spermicidal agents

Turbulent urinary flow e.g. voiding dysfunction, instrumentation.

UT obstruction – overdetention of epithelial lining and pooling of
urine

Genetic factors – defects in CXCR1 receptor

Bacterial virulence factors.
Other factors predisposing to recurrent UTI

Age <6 months

Female sex

Bladder and bowel dysfunction

Grade of reflux (III – V)

Constipation

Infrequent voiding

Poor perineal hygiene
Common pathogens causing UTI
Pathogens
Common contaminants of urine cultures
• Enterobacteriaceae
- E. coli (most common)
- K. pneumoniae
- Enterobacter spp.
- Proteus spp.
•
•
•
•
•
• Coagulase negative staphylococci
- S. saprophyticus
• Group B streptococcus
• Enterococcus spp.
Candida species
Enterococcus spp.
Gardnerella vaginalis
Mycoplasma hominus
Ureaplasma urealyticum
Clinical presentation
a. Fever
 most common symptom
 may take several days to resolve
 temp >38⁰C
b. Malodorous urine
 18 -29% of children
 may be present in children with UTI.
c. Feeding problems
d. FTT, pallor, lethagy
e. Diarrhoea and vomiting
Clinical presentation
Older children
 FOM
 Dysuria
 Hesitancy
 Enuresis
 Nausea
 Vomiting
 Flank pain
 Suprapubic tenderness
 Dribbling and prolonged voiding
Must exclude sexual abuse, particularly in female patients.
Imaging of children with UTIs

Used to detect genitourinary tract abnormalities.

Modifying correctable factors decreases number of UTIs
and prevents renal scanning.
Imaging studies

US

VCUG

Radionuclear cystography

Renal scintigraphy
 DMSA
 DTPA
 MAG3

Others e.g. CT, MRI, video urodynamics
Grades of VUR
Impact of VUR in UTI in children

VUR is the retrograde flow of urine from the bladder into
the ureter and renal pelvis.

Prevalence 1-6%

Diagnosed in 1/3 of children first UTI.

More likely to have long-term sequelae with subsequent
scarring in 10-40% of children.

Children <1 year more likely to complicate .
Management
Under 3 months
IV antibiotics until systemic signs resolve.
Followed by oral antibiotics for 7 -14 days
Over 3 months
Oral or IV depending on clinical state.
IV if systemically ill, septic appearance or persistent vomiting duration 7-10
days.
Shorter courses (3-4days) in children with cystitis
Early initiation of antibiotics decreases risk of kidney scarring.
Delayed treatment may lead to complications such as systemic sepsis and abscess
formation.
Choice depended of local sensitivity pattern.
Final choice based on pathogen identification and sensitivity testing.
Children on antibiotic prophylaxis usually develops UTIs from resistant organisms
Management of the first episode of UTI
Infant
>1 -5 years
>5years
US
US +DMSA
US
If abnormal
VCUG +DMSA
If US or DMSA abnormal
VCUG
if US abnormal
VCUG and DMSA
Common Antimicrobial agents used
Antimicrobial
agent
Parenteral
Dosage
Common adverse effects
Amoxicillin/clavulanate (>3
months)
60-100 mg/kg body weight 8
hourly
Gastrointestinal upsets, urticaria, pruritis,
stomatitis, oral and perineal candidiasis,
elevated liver enzymes, anaphylaxis
Astreonam (>3 months)
50-100 mg/kg daily
Ceftriaxone
75 mg/kg, every 24 h
Cefotaxime
150 mg/kg per day, divided every
6-8 hours
100-150 mg/kg per day, divided
every 8 hours
Phlebitis, gastrointestinal upsets, elevated liver
enzymes, eosinphilia, nephrotoxicity
Eosinophylia, elevated liver enzymes,
thrombocytosis, leukopenia, diarrhoea
Rash, pruritus, fever, eosinophilia, fever
Ceftazidine
Gentamicin
Tobramycin
Piperacillin
5 mg/kg per day, (8 or 24 hourly
>12 months)
5 mg/kg per day, divided every 8
hours
300 mg/kg per day, divided every
6-8 hours
Gastrointestinal upsets, rash, pruritus,
headaches, elevated liver enzymes,
nephrotoxicity
Nephrotoxicity, dizziness, vertigo, tennitus,
hearing loss
Same as gentamycin
Same as gentamycin
Gastrointestinal upsets, cardiac disturbances,
central nervous system effects, allergic
Common Antimicrobial agents used cont…
Antimicrobial agent
Dosage
Common adverse effects
Amoxicillin clavulanate
20-40 mg/kg per day in three doses
Diarrhea, nausea/vomiting, rash
Trimethoprim sulfamethoxazole
6-12 mg/kg trimethoprim and 30-60 mg/kg
sulfamethoxazole per day in two doses
Diarrhea, nausea/vomiting
Photosensitivity rash
Sulfisoxazole
120-150 mg/kg per day in four doses
Cefixime
8 mg/kg per day in one dose
Abdominal pain, diarrhea, Flatulence, rash
Cefpodoxime
10 mg/kg per day in two dose
Abdominal pain, diarrhea, nausea, rash
Cefprozil
30mg/kg per day in two doses
Abdominal pain, diarrhea, elevated
results on liver function tests, nausea
Cefuroxime axetil
20-30 mg/kg per day in two doses
Anaemia, eosinophilia, nephrotoxicity,
diarrhoea, elevated liver enzymes
Cephalexin
50-100 mg/kg per day in two doses
Diarrhea, headache, nausea/ vomiting,
rash
Oral
Antimicrobial Prophylaxis
 Swedish Reflux Trial – support the role for prophylaxis in girls
younger than 4 years old with grade III to IV reflux.
 No benefit in children with no reflux or low grades (I-II).
 No data in optimal duration of prophylaxis but most
prospective studies suggest 1- 2 years.
Antimicrobial Prophylaxis cont…
Randomized Intervention for Children with Vesicoureteric
Reflux (RIVUR) study
 50% reduction of risk of recurrent UTIs in children <72 months.
 Few adverse events with use of prophylaxis (>5% developed fever,
otitis media, diarrhoea, phargyngitis, rash, viral infections)
 40% developed UTI with sensitive E.coli (SMZ/TMP).
 This may suggest that compliance may have been poor in these
children.
 No statistically significant difference in the development of
TMP/SMZ–resistant UTI in both groups.
 No impact or renal scanning
Surgical correction of VUR

Indicated in following groups of children.
 Higher grades of VUR (III – V) with breakthrough infections being
Rx with prophylactic antibiotics.
 Non compliance with prophylaxis.
 Parenteral preference.
 Deteriorating kidney function

Correction may be by ureteric re-implantation or
endoscopic injection of a bulking agent
(dextranomer/hyaloronic copolymer).

Endoscopic treatment has a significant recurrence rate after
2 years necessitating repeating the procedure.
Conclusion





UTIs are common in childhood.
Requires appropriate management of acute episode as well
as prevention to minimise risk of kidney scarring as well as
CKD.
Prophylaxis may be associated with low risk of recurrent
infection in selected groups of children.
Surgical intervention required in only a small number of
patients.
Endoscopic surgery is now used increasingly in most
centres.