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Can Cran-Max® Be Used To Treat Current
Urinary Tract Infections?
Dr Anil Kapoor, Ivan Kai-Hsiang Hsia
CIHR Research Proposal:
Treatment of Uncomplicated Urinary Tract Infections
with Cranberry Extract
Urinary tract infections (UTIs) are a prevalent
and disruptive disease. North American data
of the prevalence of UTIs was estimated at approximately
3.5% of the population.[i] They account
for 1.2% of all office visits by women and 0.6%
of all office visits by men.[ii] In present
day medical practice, antibiotic therapy is
the treatment of choice for UTIs. Our better
understanding of urinary tract pathogens and
our development of new antibiotics have made
this treatment modality effective. Unfortunately,
decades of antibiotic use has given rise to
antibiotic resistance. Canadian data shows that
E. Coli, the most common pathogen causing UTIs,
has resistance rates of 41.1% to ampicillin,
18.9% to trimethoprim-sulfamethoxazole, 7.4%
to mecillinam, and 1.2% ciprofloxacin.[iii]
[iv] There are limitations to even our best
antibiotic family, the fluoroquinolones, which
include ciprofloxacin and norfloxacin. “Administration
of the fluoroquinolones to immature animals
has caused damage to the developing cartilage,
and, therefore, these agents are currently contraindicated
in children, adolescents, and pregnant or nursing
women.”[v] Therefore, it would be a prudent
course of action to investigate alternative
treatments for UTIs. The first documented use
of Cranberry as a medicine was in the 17th century,
by the European settlers who observed these
medical practices in the Native Indian community.
Recent studies have shown prophylactic usefulness
of Cranberry Extract against UTIs. It was once
believe that this was a direct result of increased
urinary acidity, but now there is evidence that
Cranberry Extract inhibits the binding of the
bacterial pathogens to the urothelium. Decreased
binding ability has been demonstrated in E.
coli, Proteus, Klebsiella, Enterobacter and
Pseudomonas.[vi] [vii] To date there is no useful
evidence regarding Cranberry Extract’s
effectiveness as a treatment for UTIs. A meta-analysis
looking for such data was performed for the
Cochrane Database of Systematic Reviews and
in its conclusion it stated that, “After
a thorough search, no randomized trials which
assessed the effectiveness of cranberry juice
for the treatment of urinary tract infections
were found. Therefore, at the present time,
there is no good quality evidence to suggest
that it is effective for the treatment of urinary
tract infections.”[viii]
Therefore, I propose to investigate and generate
data regarding Cranberry Extract as a treatment
for uncomplicated UTIs. Uncomplicated UTIs,
for the purposes of our investigation, will
be defined as an afebrile, local infection in
a patient with a structurally and functionally
normal urinary tract. This will be a comparative
study between norfloxacin and two different
doses of Cranberry Extract working under the
null-hypothesis that norfloxacin is more effective
than Cranberry Extract in the treatment of UTIs.
In the initial study, we propose to randomize
30 patients, which meet our criteria, into 3
branches.
UTI Pilot Protocol
3 arms of the study, 10 patients each
- 5 days norfloxacin 400mg PO BID (control
group)
- 5 days Cran Maxä 500mg PO OD
- 5 days Cran Maxä 500mg PO BID
Initial Visit (Day 1)
Data: Urinalysis, Culture and Sensitivity,
CBC, History and Physical (including patient
data: age, sex, etc.) Symptom score (Validated
O’leary-Sant questionnaire)
Day 2
Data: Urinalysis, Culture and Sensitivity, Symptom
score (if patient is on Cran Maxä and symptoms
worsen or there is development of a fever then
treatment is changed to antibiotics.) (otherwise
continue course)
Day 5
Data: Urinalysis, Culture and Sensitivity (if
previous Culture positive for growth then change
to antibiotics), Symptom score
Optional day 5 extension if Urinalysis positive,
but the patient feels much better (physician’s
decision)
The results will be entered into an Excel database
and a subsequent analysis using SPSS statistics
program will be performed with the completed
data. Appropriate parametric and non-parametric
statistical tests will be run to compare between
group data, i.e. control versus treatment arms,
and within group data. Examples of analytical
tests include a Chi-Squared test looking for
differences in positive/negative cultures between
control and treatment arms, an ANOVA analysis
for comparison of between group symptom scores,
and a repeated measures ANOVA to see if there
are day to day improvements within each treatment
regiment. After the analysis, we will have data
that will let us draw conclusions, on how effective,
if at all, Cranberry Extract is in treatment
of uncomplicated UTIs. We will also have data
on the time course of each treatment arm, including
information on when bacterial levels drop in
the urine and when patients start to feel better.
The study will produce data by which evidence-based
decisions, regarding the usage of Cranberry
Extract as a treatment for UTIs, can be made.
Cystitis Symptoms Index
Please circle the number that best describes
your answer to the following questions:
During the past few days, how often have you
felt the strong need to urinate with little
or no warning?
0. not at all
1. less than 1 time in 5
2. less than half the time
3. about half the time
4. more than half the time
5. almost always
During the past few days, have you had to urinate
less than 2 hours after you finished urinating?
0. not at all
1. less than 1 time in 5
2. less than half the time
3. about half the time
4. more than half the time
5. almost always
During the past few days, how often did you
most typically get up at night to urinate?
0. not at all
1. less than 1 time in 5
2. less than half the time
3. about half the time
4. more than half the time
5. almost always
During the past few days, have you experienced
pain or burning in your bladder?
0. not at all
1. less than 1 time in 5
2. less than half the time
3. about half the time
4. more than half the time
5. almost always
Interstitial Cystitis Problem Index:
During the past few days, how much has each
of the following been a problem for you?
Frequent urination during the day?
0. no problem
1. very small problem
2. small problem
3. medium problem
4. big problem
Getting up at night to urinate?
0. no problem
1. very small problem
2. small problem
3. medium problem
4. big problem
Need to urinate with little warning?
0. no problem
1. very small problem
2. small problem
3. medium problem
4. big problem
Burning, pain, discomfort, or pressure in your
bladder?
0. no problem
1. very small problem
2. small problem
3. medium problem
4. big problem
These
End Notes do not exist
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