Why is the management of UTI so controversial? Kjell Tullus Consultant Paediatric Nephrologist

Why is the management of UTI so controversial? Kjell Tullus Consultant Paediatric Nephrologist

Diagnosing a UTI More difficult then most people realise Contaminating culture Bacterial numbers Confusion with asymptomatic bacteriuria

Contamination rate Comparison of clean-voided urine and suprapubic bladder puncture in 120 infants and children 25% contamination rate in the cleanvoided specimens Aronson AS et al Acta Paediatr 1973;62:396

Contamination rates 7584 urine cultures in children <24 month Bag specimens 62.8% Catheter specimens 9.1% Al Orifi et al J Pediatr 2000;137:221

Clean-catch

Voiding with prepuce flushing

Voiding and flushing vagina

Occurrence of infantile ABU Screening bacteriuria Pyelonephritis Boys 2.5% 1.2% Girls 0.9% 1.1%

Persistence of infantile ABU - boys

Persistence of infantile ABU - girls

Difficulty How do you diagnose a UTI or not in a febrile infant with ABU and a generalised viral disease without localising symptoms?

Bacterial numbers Present cut off levels defined by Ed Kass in the 1950-ties in women with cystitis He knew that he had some false negative diagnosis but wanted from scientific purposes to only include true infections

Proportion of lower than 10 5 Swedish study in 366 infants with proven symptomatic UTI 73 (20%) had less than 10 5 bacteria on culture from suprapubic aspiration Hansson S, et al J Pediatr 199;132:180

Finnish study 477 infants 322 had bacteria on SPA Only 81% of those had more than 10 5 bacteria on a the clean voided specimen done at the same time. Of the missed children 18 showed 10 4 and 20 10 3 bacteria on the clean voided specimen Koskimies O. J Pediatr 1995;126:157

Urine culture No definitive cut-off values of bacterial count exists.

Do UTIs matter? Long term outcome Kjell Tullus Consultant Paediatric Nephrologist

Outcome historic data Mortality 20% Chronic disease 20% Cured 60% Göppert-Kattewitz 1908

Prognosis of acute pyelonephritis Renal scarring on urography 10-15% Uptake defect on DMSA 30-40%

DMSA uptake defect

Occurrence of the different types Boys Girls Primary (congenital) 18 15 Acquired 3 37 Wennerström et al J Pediatr 2000;136:30-4

Outcome measures in acute pyelonephritis Renal scarring Chronic renal failure Hypertension Complications of pregnancy

How common is CRF as a consequence of acute pyelonephritis? Very conflicting data from different countries Swedish experience of all children with UTI during 10 years in Gothenburg 232 boys and 989 girls

GFR in Gothenburg material Wennerström et al Arch Pediatr Adolesc Med 2000;154:339-45

Annual trends of reflux nephropathy in Australia Craig J et al Pediatrics 2003;105:1236-41

Outcome measures in acute pyelonephritis Outcome and importance of VUR Renal scarring Chronic renal failure Hypertension Complications of pregnancy

Hypertension 15 year follow-up of original cohort of 100 children with reflux nephropathy Seven out of the 55 patients that were possible to evaluate had hypertension Goonasekera et al the Lancet 1996;347:640-3

Hypertension - Sweden

Hypertension - Sweden (2)

Hypertension Jena and Praha Patzer et al J Pediatr 2003;142:117-22

Outcome measures in acute pyelonephritis Outcome and importance of VUR Renal scarring Chronic renal failure Hypertension Complications of pregnancy

Pregnancy complications No significant difference in the incidence of pre-eclampsia, operative delivery, prematurity or birth weight in the Gothenburg material Martinell et al BMJ 1990;300:840-4

Conclusion Renal scarring in a country with an aggressive policy of treating febrile UTI does not seem to have a high morbidity

Why should we not use prophylactic antibiotics in children with VUR Kjell Tullus Consultant Paediatric Nephrologist

Natural history of VUR

Importance of VUR for new scarring Olbing et al J Urol 1992;148:1653-6

Medical vs surgical 5-year follow-up Smellie J et al the Lancet 2001;357:1329-34

Prophylactic medications 2007 Surprisingly bad studies and thus little support that prophylaxis works in the literature BUT many of us feel that we have used it with good success in some children NICE concludes that prophylaxis can not be routinely recommended

2007-09

Meta-analyses Recurrence of symptomatic UTI

Meta-analyses Development of new scars

2009-10

Prophylactic medication Swedish study 203 children, 75 boys and 128 girls Grade III and IV VUR Age 1-2 years Treated with Prophylaxis (trimethoprim) n=69 Sting (deflux) n=66 Surveillance n=68 2 year follow-up

Outcome of reflux at 2 years Swedish study Still grade III or IV 60% prophylaxis group 30% deflux group 55% surveillance group VUR disappeared 15% prophylaxis group 40% deflux group 20% surveillance group

UTI recurrence at 2 years Swedish study Girls 18% prophylaxis group 22% deflux group 55% surveillance group Boys 8% prophylaxis group 17% deflux group 4% surveillance group Significant difference for girls but not for boys

New renal scarring at 2 years Swedish study Girls 0 prophylaxis group 4 deflux group 7 surveillance group Boys 0 prophylaxis group 1 reflux group 1 surveillance group Significant difference for girls but not for boys

Prophylactic medication Australian study 576 children, younger than 18 years Placebo controlled study, 12 month follow-up Included all kinds of UTI Median age 14 month 64% girls 42% VUR Analysed recurrence of UTI but not scars NEJM Craig et al 2009;361:1748-59

Prophylactic medication Time to Symptomatic Urinary Tract Infection (UTI) (Primary Outcome) Australian study Craig J et al. N Engl J Med 2009;361:1748-1759

Effect on scarring Study too small despite 576 children to be able to evaluate the effect on later scarring The effect is thus small if any

What to do 2011? Do not treat most children with VUR Treat girls with VUR III-V with prophylaxis until the age of 3-4 years