Probiotics in Girls With Spina Bifida

In children with spina bifida and neurogenic bladder dysfunction, the need for intermittent
bladder catheterization increases the risk of bacteriuria. In many patients, this leads to a
clinically significant urinary tract infection (UTI). Many of these children are placed on
long term, low dose antibiotic suppression to prevent recurrent urinary infection.
Unfortunately, bacteriuria often persists despite daily antibiotic therapy, and breakthrough
UTIs are common. Furthermore, this approach carries the potential for deleterious side
effects, and may promote the development of antibiotic-resistant bacteria.

UTI in girls occur when virulent bacteria migrate from the rectum and colonize the vagina
and peri-urethral mucosa, thus gaining access to the bladder. In girls with spina bifida,
access to the bladder is greatly facilitated by catheter passage. Antibiotic prophylaxis
relies on maintaining a low dose of antibiotic in the urinary stream, which decreases
peri-urethral colonization, and prevents proliferation of bacteria after they gain access to
the bladder. An alternative approach to daily antibiotic prophylaxis is to decrease the risk
of urinary colonization with virulent bacteria by supplementing the normal bacteria flora
with non-infection causing strains of bacteria.

Probiotics are dietary supplements containing potentially beneficial bacterial strains such
as Lactobacillus. The safety of oral administration of probiotics has been demonstrated in
several studies over the last 30 years. Studies using Lactobacillus rhamnosus GG, a
probiotic introduced in the late 1980s to alleviate diarrhea, have shown promising results
when used for UTI prevention. In one study, researchers found that the subjects consuming GG
drinks had fewer episodes of UTI compared to those women not receiving probiotics. A
placebo-controlled study in premature infants also used GG in an attempt to prevent UTI. The
number of urinary infections was reduced but statistically the difference was not
significant. Finally, a recent randomized clinical trial demonstrated that the rate of UTI
in children taking prophylactic antibiotics was similar to that of patients taking
Lactobacillus acidophilus alone. The efficacy of probiotic usage in the spina bifida
population has not been reported.

Clinical trials have suggested that oral ingestion of the probiotic strains Lactobacillus
reuteri RC-14 and Lactobacillus rhamnosus GR-1 results in vaginal colonization and
prevention of adult UTI, potentially by inhibiting uropathogen ascension from the vagina to
the urinary tract.

A total of 60 patients will be enrolled for this pilot study, half of whom will be
randomized to receive probiotics and the reminder of which will receive placebo [1:1 ratio;
50% chance of being in each group (A and B)]. Treatment assignment will be double blinded
and will last 6 months.

Inclusion Criteria:

- Girls

- Age 3 months to 18 years

- Spina bifida as a sole urologic diagnosis

- Informed consent and assent (7 years of age and older)

Exclusion Criteria:

- Males

- Females over 18 years and older

- Prophylactic antibiotics

- Immunosuppression from corticosteroids, transplant recipients or children with
congenital immunodeficiencies

- Poorly controlled diabetes

- Untreated HIV infection

- Chronic indwelling catheters in the bladder

- Malnourished

- Pregnancy

- Any form of urinary division other than appendicovesicostomies is not permitted

- Bladder augmentation

- Unresolved reflux