Hatice Mutlu, Zelal Ekinci

1. A Prospective Controlled Trial with Cranberry Capsules: Prevention of UTI in Children with Neurogenic Bladder Hatice Mutlu, Zelal Ekinci Kocaeli University School of Medicine, Department of Pediatric Nephrology, Kocaeli, TURKEY

2. Background • Cranberry juice • traditionally used to reduce recurrent UTI • mechanism of action not fully understood • the only active moieties discovered are trimeric A-type proanthocyanidins • appears to prevent UTIs by inhibition of the binding of the P-fimbria of uropathogens

3. Background • Children with neurogenic bladder • UTI is a leading cause of morbidity • symptomatic UTI and its possible association with renal damage • long-term antibiotic prophylaxis has not shown significant benefit This trial was designed to evaluate the effects of cranberry capsules for the prevention of UTI in children with neurogenic bladder.

4. Patients and Methods • Placebo-controlled crossover trial • Between 1.09.2009-1.09.2010 • The study was conducted according to the Declaration of Helsinki • Approved by The Human Research Ethical Committee of Kocaeli University Hospital • Informed consent was obtained from the patient and/or from the parents of each patient

5. Patients and Methods • Inclusion Criteria • Children with neurogenic bladder caused by meningomyelocele • Age ≤ 18 years • Followed up with anticolinergic drugs ( 0.6 mg/kg) and clean intermittent catheterization (4/day) • Evaluated urodynamically: overactive detrusor with increased sphincter tonus

6. Twenty patients were elected from our data base according to urodynamic findings to form a homogenous group and to eliminate the potential differences which could affect the risk of infection rate according to bladder pathology.

7. Patients and Methods • 6 months placebo (1 capsule/day) • 6 months cranberry extract capsules (1 capsule/day, GNC company) • followed in the pediatric nephrology outpatient clinic every month for the signs and symptoms of UTI • Symptomatic UTI (European guidelines,2003) • fever ≥ 38.5 C, • abdominal pain, • change in continence pattern or change in the color or odor of urine • associated with a positive urine culture. • Urinalysis and culture performed each monthly exam • A positive urine culture : ≥ 104 colony-forming units/ml. • Pyuria:≥ 5 WBCs/HPF on microscopic examination of a centrifugated urine.

8. Patients and Methods • Each patient and parent trained for the symptoms of symptomatic UTI • In case of symptomatic UTI, patients and parents trained for unscheduled admission • UTI:treated with antibiotics and study medications were continued • Patient compliance: assessed by counting the remaining pills at each monthly visit • Infection rate:before and after cranberry capsule usage as a number of infections per year • Review of the medical records: for the presence of vesico-ureteral reflux(VUR) on VCUG and scar on DMSA scan • Group comparisons: performed with Wilcoxon Test

9. Patients’ Characteristics

10. Infection rates of patients during placebo and cranberry usage Infection rate is presented as mean ± SD (median)

11. Number of patients with pyuria during placebo and cranberry usage

12. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2008, 23;(1):CD001321. • There is some evidence that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period, particularly for women with recurrent UTIs. • It's effectiveness for other groups is less certain. • The large number of dropouts/withdrawals indicates that cranberry juice may not be acceptable over long periods of time. • It is not clear what is the optimum dosage or method of administration (e.g. juice, tablets or capsules). • Further properly designed studies with relevant outcomes are needed.

13. Opperman EA. Cranberry is not effective for the prevention or treatment of urinary tract infections in individuals with spinal cord injury. Spinal Cord. 2010;48(6):451-6. • Five studies (four randomized clinical control-three trials using cranberry tablets vs placebos and one using cranberry juice-and one pilot study using cranberry juice) • Three studies reported no statistically significant effect of cranberry tablets in urinary PH, urinary bacterial count, urinary WBC count,and episodes of symptomatic UTI. • A fourth study showed that cranberry juice intake significantly reduced biofilm load compared with baseline. • A final study reported fewer UTIs during the period with cranberry extract tablets vs placebo.

14. Hess MJ, Hess PE, Sullivan MR, Nee M, Yalla SV. Evaluation of cranberry tablets for the prevention of urinary tract infections in spinal cord injured patients with neurogenic bladder. Spinal Cord. 2008;46(9):622-6. • Forty-seven subjects completed the trial. • We found a reduction in the likelihood of UTI and symptoms for any month while receiving the cranberry tablet (P<0.05 for all). • The frequency of UTI was reduced to 0.3 UTI per year vs 1.0 UTI per year while receiving placebo.

15. Two randomised,controlled trial • Children with spinal cord disease requiring CIC • 15 and 21 patients; 3 months and 6 months • There were no significant intertreatment differences in the rates of asymptomatic bacteriuria and UTIs • Foda MM, Middlebrook PF, Gatfield CT, Potvin G, Wells G, Schillinger JF. Efficacy of cranberry in prevention of urinary tract infection in a susceptible pediatric population. Can J Urol. 1995 ;2(1):98-102. • Schlager TA, Anderson S, Trudell J, Hendley JO. Effect of cranberry juice on bacteriuria in children with neurogenic bladder receiving intermittent catheterization. J Pediatr. 1999 ;135(6):698-702.

16. Elliott SP, Villar R, Duncan B. Bacteriuria management and urological evaluation of patients with spina bifida and neurogenic bladder: a multicenter survey. J Urol. 2005 ;173(1):217-20. • A survey conducted of 169 spina bifida clinics in the US • 59 (39 %) clinics returned the survey • 57 % of respondents recommendedcranberry to prevent UTIs • 50 % believed that these products were of benefit.

18. Conclusion • Decrease in infection rate, • Decrease in frequency of pyuria is significant. • Cranberry capsules could be an encouraging option for the prevention of UTI in children with neurogenic bladder caused by meningomyelocele.

19. Thank you for your attention!