Is antibiotic prophylaxis of any use in nephro-urology? Giovanni Montini Pediatric Nephrology and Dialysis Unit University of Milan Italy

Size: px

Start display at page:

Download "Is antibiotic prophylaxis of any use in nephro-urology? Giovanni Montini Pediatric Nephrology and Dialysis Unit University of Milan Italy"

Audra Thornton
5 years ago
Views:

1 Is antibiotic prophylaxis of any use in nephro-urology? Giovanni Montini Pediatric Nephrology and Dialysis Unit University of Milan Italy

2 UTI_VUR

3 Bacteria and Humans: diverse behaviours!! Bacteria Humans Extremely numerous Memorise generational experiences within a few hours Capacity to transfer vast quantities of information in seconds Extraordinary ability to adapt under the selective pressure of antibiotics Outstanding collaboration Often few and isolated Endless discussions!! Difficulty in confronting and resolving issues Tendency to maintain the same diagnostic and therapeutic approaches Scarce collaboration for the most part

10 Causes of CKD (n=1197) Heredithary nephropathies 15.4% Others 13.2% Hypodysplasia and VUR 24.7% PUV 10.2% HUS 3.6% Glomerulopathies 6.8% Other uropathies Hypodysplasia 12.2% 13.9% ItalKid 2003

11 Cumulative % Age at diagnosis of vesicoureteral reflux (as cumulative percent) by sex in children with CRF (n:187) , , ,5 9, months years Age at diagnosis of VUR males females ItalKid 2002

12 176 CAKUT children Gonzalez Celedon PN 2007

13 n = % 5.7% 8% 27.5% 42.8%

14 The old concept G. Montini, I. Hewitt and K Tullus

15 J De Bessa, J Urol 2015

17 May 4, 2014

18 71/126 toilettrained children VUR GRADE II-III = 80% Hoberman, NEJM 2014

19 RESULTS: primary endpoint The treatment proved statistically significant, but of doubtful clinical value: requiring 16 or 22 patient years of antibiotics to prevent 1 UTI or 1 febrile UTI, respectively

20 RESULTS p. NS p < 0,001 The treatment group had in excess of 600 years of prophylaxis without a demonstrable effect on scar formation but a much higher propensity to induce bacterial resistance

22 Guidelines Antibiotic prophylaxis Others interventions NICE Not for routine use Treat dysfunctional elimination syndromes and constipation Drink an adequate amount of fluid Do not delay voiding AAP Not for routine use Not considered ISPN For reflux III-V Recurrent febrile UTI* Not considered * 3 febrile UTIs within 12 months

24 Previous studies Reflux grades of all RCTs of antibiotic prophylaxis VUR grade n I-II 777 III 577 IV 172 V 5 Total 2080

25 THE PREDICT TRIAL Antibiotic Prophylaxis and REnal Damage In Congenital abnormalities of the kidney and urinary Tract Giovanni Montini Nefrologia e Dialisi Pediatrica Policlinico Sant Orsola-Malpighi Bologna

26 PREDICT Trial: INCLUSION/EXCLUSION CRITERIA INCLUSION CRITERIA Age 1-4 months (until the 20 th week of post-natal age!) Gestational age > 35 weeks GFR (according to Schwartz) > 15 ml/min/1.73 m 2 Grade III to V vesico-ureteral reflux No previous symptomatic UTI EXCLUSION CRITERIA - Neurogenic bladder - Myelomeningocele - Uretero-pelvic junction and/or uretero-vescico junction obstruction - Malformations leading to potential voiding disturbances - Urethral valves

27 CAKUT (prenatal or postnatal US screening) PRE-RANDOMIZATION renal function, US, VCUG and DMSA GROUP A Follow-up 326 ( 436 )PATIENTS with VUR III-V RANDOMIZATION STRATIFICATION Renal damage GROUP B Antibiotic prophylaxis 24 months (renal function, US + DMSA +/- VCUG+ BMI) 36 months FOLLOW-UP 60 months (renal function, US + DMSA + VCUG+ BMI)

28 END-POINTS Primary end point: first symptomatic urinary tract infection during the 24- month observation period. Secondary end point: febrile UTIs, number of new renal scars at the 2 years follow-up DMSA scan, development of renal function, hypertension and/or proteinuria, anatomical growth of the kidneys at 2 and 5 years follow-up, evaluation of the natural course of renal function for hypo-dysplastic kidneys during the first 5 years of life and evaluation of BMI at 2 and 5 years of age.

29 ANTIBIOTIC PROPHYLAXIS Nitrofurantoin (1.5-2 mg/kg/day) Co-amoxiclav (15 mg/kg/day) Cefixime (2 mg/kg/day) Trimetropim/sulfametoxazole (2.5 mg/kg/day) ONCE DAILY AT EVENING According to the local antibiotic resistance pattern of E. coli Each single patient may switch from one antibiotic to another.

30 Inpatients UC: resistance to E.coli Alberici I et al EUR J Ped 2015

31 STATE OF THE ART: COUNTRIES 14 EUROPEAN COUNTRIES

32 GUT MICROBIOTA Aims: - explore the modification in gut microbiota induced by antibiotic exposure in early infancy - Modifications in the pattern of resistance genes coded by gut microbiota (gut resistome profile). collect and freeze a STOOL SAMPLE from every patient 8 time points: (0, 4, 8, 12, 24, 36, 48, 60 months)

33 Current Understanding of Febrile Urinary Tract Infections and Renal Scarring. Montini G et al. N Engl J Med 2011;365:

34 Cystitis: antibiotic prophylaxis - If frequently recurrent but > antibiotic resistance - Short periods (1-3 months) - Main aim is to remove symptoms secondary to cystitis and then to evaluate bladder function with no concomitant infection - Cranberry??

36 Results Mean duration of follow-up was 47±30 months (12 to 78 months). The mean age of diagnosis in the cases that were not discovered prenatally was 10±19 months (1 week 77 months). 24%

37 During follow-up, a high rate of spontaneous regression was observed. At 7 years of follow-up, 70% of POM had regressed spontaneously

38 What about prophylaxis? In the first year of life, 30/44 received antibiotic prophylaxis. 7 UTIs occurred during 199 patient months with prophylaxis 19 UTIs during 244 patient months without prophylaxis reduction of UTI incidence on proph by 55% (0.94 vs UTIs per year, p<0.05) Prophylaxis appeared particularly effective in the first 6 months of life, where an 83% reduction of UTI rate was found UTIs/year without prophylaxis In the second year of life 38% received antibiotic prophylaxis 0.14 UTIs/year without prophylaxis In the third year of life 21% received antibiotic prophylaxis

39 NO Prophylaxis Hydronephrosis Neurogenic bladder and CIC Non dilating Refux

40 YES Prophylaxis Dilating Reflux Non Refluxing Megaureter Recurrent cystitis Urethral valves

41 Is antibiotic prophylaxis of any use in nephro-urology? Giovanni Montini Pediatric Nephrology and Dialysis Unit University of Milan Italy

Urinary tract infections in children with CAKUT and introduction of the PREDICT trial Giovanni Montini, Bologna, Italy.

Urinary tract infections in children with CAKUT and introduction of the PREDICT trial Giovanni Montini, Bologna, Italy giovanni.montini@aosp.bo.it Causes of CKD (n=1197) Heredithary nephropathies 15.4%