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