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Hôpital Trousseau
Paris
Shall we choose a prophylaxis or not ?
Tim Ulinski
ESPN Lyon 2008Common and still challenging issues about UTI
Department of Pediatric Nephrology, Hôpital Trousseau, Paris, France
Hôpital Trousseau
Paris
Vesico Ureteral Reflux
Acute Pyelonephritis
Renal Scar
« Basic Principle »
Hôpital Trousseau
Paris
2 consequences
Systematic searchfor VUR since the
1st acute pyelonephritis
Systematic prophylactic antibiotics once we have
detected VUR
Hôpital Trousseau
Paris
CAKUT
Urinary TractDilation
Vesico-Ureteral Reflux
Non-functional renal parenchyma
« Scars »
Primary problems
« The hen and egg problem »
Secondary problems
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 theconsequence of pyelonephritis( )
Prophylaxis ?
Hôpital Trousseau
Paris
Since 2001: Are the current protocols really adequat Since 2001: Are the current protocols really adequat (or dogmatic) ?(or dogmatic) ?
Since 2001: Are the current protocols really adequat Since 2001: Are the current protocols really adequat (or dogmatic) ?(or dogmatic) ?
1) In case of VUR:
systematic prophylactic antibiotics ?
2) After a first acute pyelonephritis:
Is voiding cystography necessary ?
Hôpital Trousseau
Paris
Benefits of systematic prophylaxisBenefits of systematic prophylaxisBenefits of systematic prophylaxisBenefits of systematic prophylaxis
Before 2000
Most consensus conferences:
Based on:
PRO systematic prophlaxis
- Expert opinions
- But no prospective studies
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 ?Benefits of systematic prophylaxis ?Benefits of systematic prophylaxis ?Benefits of systematic prophylaxis ?
There is no proof of efficacy
The first doubts….
Hôpital Trousseau
Paris
- 2002 S. Hellestein et alPediatr Nephrol, 2002 ; 17 : 506-510
- 2006 E. Garin et alPediatrics, 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
Hôpital Trousseau
Paris
Conclusion of these papersConclusion of these papers
Prophylactic antibiotics do not reduce the incidence of acute pyelonephritis
if VUR is of low grade ( ≤ III)
Hôpital Trousseau
Paris
Study Trousseau HospitalStudy 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%
Hôpital Trousseau
Paris
VUR of high grade (>3)VUR of high grade (>3)VUR of high grade (>3)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=
Hôpital Trousseau
Paris
Prophylaxis in case of high grade reflux Prophylaxis in case of high grade reflux Prophylaxis in case of high grade reflux Prophylaxis in case of high grade reflux
• Pennesi 2008, Pediatrics• ESPN - Palermo 2006
- Prospective
- 100 children
No benefit of prophylactic antibioticsBut only very few patients with high grade reflux
Hôpital Trousseau
Paris
- Study of the « international reflux study group »
- Only very few prospectiv studies
Prophylaxis in case of high grade reflux Prophylaxis in case of high grade reflux Prophylaxis in case of high grade reflux Prophylaxis in case of high grade reflux
Maintain antibiotic prophylaxis in high grade reflux
Caution
Hôpital Trousseau
Paris
« … but at least they won’t harm »
Prophylactic Antibiotics : ‘No benefits ?’ Prophylactic Antibiotics : ‘No benefits ?’ Prophylactic Antibiotics : ‘No benefits ?’ 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”
Hôpital Trousseau
Paris
VUR Grade I - III No Prophylaxis No cystography after 1st acute pyelonephritis
Because there isno therapeutic consequence for 90% of patients
No efficacy of prophylactic antibiotics- Consequences -
Hôpital Trousseau
Paris
Does ‘Deflux’ change the attitudeDoes ‘Deflux’ change the attitudetowards prophylactic antibiotics ? towards prophylactic antibiotics ? Does ‘Deflux’ change the attitudeDoes ‘Deflux’ change the attitudetowards prophylactic antibiotics ? towards prophylactic antibiotics ?
• YES: Easy to perform« As good as prophylactic antibiotics »No daily medicationNo resistance to antibiotics
• NO: Because it « works better in low grade reflux »
« …. and prophylactic antibiotics are useless anyway in low grade reflux »
Hôpital Trousseau
Paris
Preventing UTI in boysPreventing UTI in boysPreventing UTI in boysPreventing 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, PediatricsWiswell et al 1985, Pediatrics
“dramatic risk reduction of UTI among circumcised children”
Hôpital Trousseau
Paris
Prophylactic Antibiotics and Prophylactic Antibiotics and « Evidence Based Medicine » « Evidence Based Medicine » Prophylactic Antibiotics and Prophylactic Antibiotics and « Evidence Based Medicine » « 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 prophylacticantibiotics are useless in high grade reflux
Hôpital Trousseau
Paris
« Evidence Based Medicine »« Evidence Based Medicine »versusversus
« Personal Experience » « Personal Experience »
« Evidence Based Medicine »« Evidence Based Medicine »versusversus
« Personal Experience » « Personal Experience »
Is it possible to transform personal experience into evidence ?
Can we identify patients who would benefit from prophylactic antibiotics ?
Can we identify patients who would benefit from prophylactic antibiotics ?
Hôpital Trousseau
Paris
Can we identify patients who would benefit Can we identify patients who would benefit from prophylactic antibiotics ? from prophylactic antibiotics ?
Can we identify patients who would benefit Can we identify patients who would benefit from prophylactic antibiotics ? 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) « C
lass
ical »
• Particularities of urothelium ?
• Immunological dysfunction ?
« F
utu
r »
?
Hôpital Trousseau
Paris
0.6
2.3
1.0
The higher the PCT,the higher the risk for high grade reflux
P<0.05N=136
No VUR VUR ≤ 3 VUR 4+5
Leroy et al.Pediatrics 2005
Falsepositive
Hôpital Trousseau
Paris
Possible « remaining indications » for prophylactic antibiotics
Possible « remaining indications » for prophylactic antibiotics
• High grade reflux
• Intrarenal reflux
• Recurrency of UTI after withdrawal of prophylaxis
• Recurrent cystitis
Hôpital Trousseau
Paris
« … and what about Cranberry juice ? »
Hôpital Trousseau
Paris