urinary tract infections in children: a changing paradigm r bhimma department of paediatrics and...
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Urinary Tract Infections in Children: a Changing Paradigm
R Bhimma
Department of Paediatrics and Child Health
Nelson R Mandela School of MedicineUniversity of KwaZulu-Natal
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 renal scarring HPT and CKD.
Early guidelines advocated aggressive treatment and extensive imaging to detect VUR and kidney scarring.
Introduction
Renal Scarring
Normal kidney Scarred kidney
In the last decade there is a more targeted approach to UTIs
More judicious use of resources
Harmful procedures and interventionsare avoided
Introduction
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
Concerns
Varies according to: method of urine collection number of bacterial species clinical presentation.
Culture negative urine: prior antibiotic Rx complete UT obstruction infected cyst
Diagnosis of UTI
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.
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)
Occult UTI
Children with fever (5% baseline risk)
Children who have had onePrevious UTI (20% baseline risk)
Positive Negative Positive Negative
Post test probability of UTI Post test Probability of UTI
DipstickLeucocyte esterase
alone24 2 72 9
Nitrite alone 56 3 91 18
Leucocyte esteraseand nitrite
54 3 90 19
Leucocyte esteraseor nitrite
18 1 64 6
MicroscopyWhite cell count 22 2 69 11
Bacteria 37 1 82 5
Gram stainedbacteria 55 0.3 90 19
Diagnosis of UTI – dipsticks and microscopy Post-test probability of UTI with varying baseline risk of UTI for the common near patient tests
Collection method
Colony forming units
per litre
Number ofbacterial species
Definite UTI
Voided samplesBag collectionMidstream catch
≥10⁸ 1
Catheter samples ≥ 10⁷ 1
Suprapubic bladder aspirate
Any number 1
Microbiological threshold for the diagnosis of UTI
Williams G et al. J Paediatr Child Health (2012), 48:296-301
Collection method Colony forming unitsper litre
Number ofbacterial species
Probable UTI
Voided samples Bag collection
≥10⁷ 1
Midstream catch
≥10⁸ 1
Clean catch ≥10⁶ 1
Catheter sample
≥10⁷ 2
Suprapubic bladder aspiration
Any number 2
Microbiological threshold for the diagnosis of UTI
Williams G et al. J Paediatr Child Health (2012), 48:296-301
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
Asymptomatic
bacteraemia
Is defined as infection limited to the urethra and bladder; symptoms include frequency, urgency, dysuria, lower abdominal discomfort or pain and or cloudy urine.
Is defined as the presence of high ≥ 38.5°C
and/or systemic involvement, except in some very young infants
Classification of UTI cont…
Cystitis
Acute pyelonephrit
is
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.
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…
Simple UTI
Severe UTI
Is defined as the invasion of a structurally and functionally normal urinary tract by a non-resident infectious organism.
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.
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…
Uncomplicated UTI
Complicated UTI
Recurrent UTI
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.
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
Is defined as a renal mass caused by focal infection with liquefaction and may lead to the development of a renal abscess later on.
Classification of UTI cont…
Atypical UTIs
Relapsing UTI
Acute lobar nephronia (acutelobar nephritis)
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
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.
Pathogenesis of UTI cont..
Age <6 months
Female sex
Bladder and bowel dysfunction
Grade of reflux (III – V)
Constipation
Infrequent voiding
Poor perineal hygiene
Other factors predisposing to recurrent UTI
Pathogens Common contaminants of urine cultures
• Enterobacteriaceae - E. coli (most common) - K. pneumoniae - Enterobacter spp. - Proteus spp.
• Candida species• Enterococcus spp.• Gardnerella vaginalis• Mycoplasma hominus• Ureaplasma urealyticum
• Coagulase negative staphylococci - S. saprophyticus
• Group B streptococcus
• Enterococcus spp.
Common pathogens causing UTI
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.
Clinical presentation
Used to detect genitourinary tract
abnormalities.
Modifying correctable factors decreases number
of UTIs and prevents renal scanning.
Imaging of children with UTIs
US
VCUG
Radionuclear cystography
Renal scintigraphy
DMSA
DTPA
MAG3
Others e.g. CT, MRI, video urodynamics
Imaging studies
Grades of VUR
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 .
Impact of VUR in UTI in children
Management
Infant >1 -5 years >5years
US US +DMSA US
If abnormal If US or DMSA abnormal if US abnormal
VCUG +DMSA VCUG VCUG and DMSA
Management of the first episode of UTI
Common Antimicrobial agents used
Antimicrobial agent
Dosage
Common adverse effects
Parenteral
Amoxicillin/clavulanate (>3
months)
60-100 mg/kg body weight 8 hourly
Gastrointestinal upsets, urticaria, pruritis, stomatitis, oral and perineal candidiasis, elevated liver enzymes,
anaphylaxisAstreonam (>3
months)50-100 mg/kg daily Phlebitis, gastrointestinal upsets,
elevated liver enzymes, eosinphilia, nephrotoxicity
Ceftriaxone 75 mg/kg, every 24 h Eosinophylia, elevated liver enzymes, thrombocytosis, leukopenia, diarrhoea
Cefotaxime 150 mg/kg per day, divided every 6-8 hours
Rash, pruritus, fever, eosinophilia, fever
Ceftazidine 100-150 mg/kg per day, divided every 8 hours
Gastrointestinal upsets, rash, pruritus, headaches, elevated liver enzymes,
nephrotoxicityGentamicin 5 mg/kg per day, (8 or 24
hourly >12 months)Nephrotoxicity, dizziness, vertigo,
tennitus, hearing lossTobramycin 5 mg/kg per day, divided
every 8 hoursSame as gentamycinSame as gentamycin
Piperacillin 300 mg/kg per day, divided every 6-8 hours
Gastrointestinal upsets, cardiac disturbances, central nervous system effects, allergic reactions, micturition
disorders.
Antimicrobial agent Dosage Common adverse effects
OralAmoxicillin clavulanate 20-40 mg/kg per day in three
dosesDiarrhea, 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
Common Antimicrobial agents used cont…
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
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
Antimicrobial Prophylaxis cont…
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.
Surgical correction of VUR
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.
Conclusion