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