1. Hôpital Trousseau Paris Shall we choose a prophylaxis or not ? Tim Ulinski ESPN Lyon 2008 Common and still challenging issues about UTI Department of Pediatric Nephrology, Hôpital Trousseau, Paris, France

2. Hôpital Trousseau Paris Vesico Ureteral Reflux Acute Pyelonephritis Renal Scar « Basic Principle »

3. Hôpital Trousseau Paris 2 consequences Systematic search for VUR since the 1 st acute pyelonephritis Systematic prophylactic antibiotics once we have detected VUR

4. Hôpital Trousseau Paris CAKUT Urinary Tract Dilation Vesico-Ureteral Reflux Non-functional renal parenchyma « Scars » Primary problems « The hen and egg problem » Secondary problems

5. Hôpital Trousseau Paris Vesico Ureteral Reflux Acute Pyelonephritis Renal Scar « Basic Principle » or « Old Dogma » ? « ….a bit of both » Not a sufficient factor ( ) May not be the consequence of pyelonephritis ( ) Prophylaxis ?

6. Hôpital Trousseau Paris Since 2001: Are the current protocols really adequat (or dogmatic) ? 1) In case of VUR: systematic prophylactic antibiotics ? 2) After a first acute pyelonephritis: Is voiding cystography necessary ?

7. Hôpital Trousseau Paris Benefits of systematic prophylaxis Before 2000 Most consensus conferences: Based on: PRO systematic prophlaxis - Expert opinions - But no prospective studies

8. Hôpital Trousseau Paris Antibiotics for the prevention of urinary tract infections in children : a systematic review of randomized controlled trials G. Williams, A. Lee, J. Craig J. Pediatr, 2001 ; 138 : 868-874 Benefits of systematic prophylaxis ? There is no proof of efficacy The first doubts….

9. Hôpital Trousseau Paris - 2002 S. Hellestein et al Pediatr Nephrol, 2002 ; 17 : 506-510 - 2006 E. Garin et al Pediatrics, 2006, 117 : 626-632 - 2008 G. Roussey-Kesler et al Journal of Urology, 2008, 179 : 674-679 Proof of non-efficacy Prospective studies Double blind Inclusion of >200 children

10. Hôpital Trousseau Paris Conclusion of these papers Prophylactic antibiotics do not reduce the incidence of acute pyelonephritis if VUR is of low grade ( III)

11. Hôpital Trousseau Paris Study Trousseau Hospital 58 children with VUR I – III Stop of prophylaxis when children were toilet trained Observation period 27 months No infection: 53 children Cystitis: 3 children Acute pyelonephritis: 2 children 91%

12. Hôpital Trousseau Paris VUR of high grade (>3) - International reflux study in children : Prospective study over 10 years But: no « control » group with « NO » treatment Prophylactic antibiotics surgery =

13. Hôpital Trousseau Paris Prophylaxis in case of high grade reflux Pennesi 2008, Pediatrics ESPN - Palermo 2006 - Prospective - 100 children No benefit of prophylactic antibiotics But only very few patients with high grade reflux

14. Hôpital Trousseau Paris - Study of the « international reflux study group » - Only very few prospectiv studies Prophylaxis in case of high grade reflux Maintain antibiotic prophylaxis in high grade reflux Caution

15. Hôpital Trousseau Paris « … but at least they wont harm » Prophylactic Antibiotics : No benefits ? Prophylactic Antibiotics may increase the number of resistant strains. ? Conway et al, 2007, JAMA: Antimicrobial prophylaxis was not associated with decreased risk of recurrent UTI, but was associated with increased risk of resistant infections

16. Hôpital Trousseau Paris VUR Grade I - IIINo Prophylaxis No cystography after 1 st acute pyelonephritis Because there is no therapeutic consequence for 90% of patients No efficacy of prophylactic antibiotics - Consequences -

17. Hôpital Trousseau Paris Does Deflux change the attitude towards prophylactic antibiotics ? YES: Easy to perform « As good as prophylactic antibiotics » No daily medication No resistance to antibiotics NO: Because it « works better in low grade reflux » « …. and prophylactic antibiotics are useless anyway in low grade reflux »

18. Hôpital Trousseau Paris Preventing UTI in boys - Risk factor : Prepuce treatment of preputial abnormalities The efficacy of circumcision in decreasing the incidence of UTI in male infants is much less questioned. Ginsburg et al 1982, Pediatrics Wiswell et al 1985, Pediatrics dramatic risk reduction of UTI among circumcised children

19. Hôpital Trousseau Paris Prophylactic Antibiotics and « Evidence Based Medicine » There is no evidence that prophylactic antibiotics are useful in low and high grade reflux There is evidence that prophylactic antibiotics are useless in low grade reflux ( Grade 3) There is not yet much evidence that prophylactic antibiotics are useless in high grade reflux

20. Hôpital Trousseau Paris « Evidence Based Medicine » versus « Personal Experience » Is it possible to transform personal experience into evidence ? Can we identify patients who would benefit from prophylactic antibiotics ?

21. Hôpital Trousseau Paris Can we identify patients who would benefit from prophylactic antibiotics ? High grade reflux ? Intrarenal reflux ? Young Age ? Recurrency of UTI after withdrawal of antibiotic prophylaxis ? Severe sequelae of previous urinary tract infections ? (as long as surgery is not possible) « Classical » Particularities of urothelium ? Immunological dysfunction ? « Futur »

22. Hôpital Trousseau Paris 0.60.6 2.32.3 1.01.0 The higher the PCT, the higher the risk for high grade reflux P<0.05 N=136 No VURVUR 3VUR 4+5 Leroy et al. Pediatrics 2005 False positive

23. Hôpital Trousseau Paris Possible « remaining indications » for prophylactic antibiotics High grade reflux Intrarenal reflux Recurrency of UTI after withdrawal of prophylaxis Recurrent cystitis

24. Hôpital Trousseau Paris « … and what about Cranberry juice ? »

25. Hôpital Trousseau Paris