A pilot study on symptomatic treatment of uncomplicated urinary tract infections in general practice.

Symptoms of urinary tract infections (UTIs) are among the most frequent
clinical presentations in primary care with annual incidences ranging from 30
to 40 per 1000 patients [1]. Around 90% of those presenting are adult women.
The most important pathogen in these female primary care patients is
Escherichia coli (70 * 80%). Other pathogens like Proteus mirabilis, Klebsiella
pneumoniae and Staphylococcus saprofiticus are present in about 20 to 30%.
Bacterial resistance of these pathogens is a major problem in all EU countries.
E.coli resistance to ampicillin ranges from 25% to 50%, to trimethoprim up to
25%, and to nitrofurantoin about 1 to 7% [2, 3,4,5]. Because of this rising
problem of bacterial resistance it is important to restrict antibiotic use in
UTIs as much as possible.
It has been suggested that uncomplicated UTIs are self-limiting [6] and
symptomatic treatment may be effective in these patients. Also, it is known
from current practice that a significant number of women with symptoms of a UTI
wait a couple of days, before consulting their GP if the symptoms persist. In
addition, many women follow a wait-and-see policy when they start having
symptoms and experience that the symptoms usually disappear within few days.

Two placebo-controlled trials regarding urinary tract infections in primary
care were found. They both showed that antibiotic treatment was significantly
more effective than placebo in achieving bacteriological cure and symptomatic
relief in patients with uncomplicated UTIs.[7,8] However, the control groups
did not receive adequate systematic and symptomatic treatment. In the study by
Christiaens et al., there was one clinical diagnosis of pyelonephritis in the
placebo group after three days. The placebo group included 38 participants.[7]
Ferry et al. also found that the risk of complications was low; two patients
developed pyelonephritis, one receiving antibiotics for seven days and one
receiving placebo. Their control group included 425 participants, the
antibiotics group included 1143 subjects.[8] Thus it is still unknown whether
antibiotic treatment of uncomplicated UTI has relevant advantages compared with
symptomatic treatment. In addition, the frequent occurrence of side effects is
a relevant problem in using antibiotics.
Subsequently the questions arises if symptoms of an uncomplicated UTI will
diminish equally fast using adequate symptomatic treatment and drinking enough
liquids, compared to using antibiotics. Therefore, we are currently preparing a
randomised clinical trial comparing the effects of antibiotic treatment with
symptomatic treatment in adult women with uncomplicated UTIs. Before conducting
such a trial it is important to study acceptability and feasibility of
structured and adequate symptomatic treatment in adult women with uncomplicated
UTIs.

The objective of the proposed pilot study is to explore acceptability and
feasibility of structured and adequate symptomatic treatment in adult women
with uncomplicated UTI.

The study is an pilot study. Participating GPs will ask women between 18 and 45
years old who present with an uncomplicated UTI to participate in this study.
Following the 'NHG-standaard', the UTI will be confirmed using dipstick-testing
and subsequently by dipslide (uricult) if nitrite is found to be negative.
After testing, urine samples will be destroyed according to standard procedures
in the GP practices. Patients will be included after giving informed consent.
Subjects will be advised to drink at least 2 litres of liquids per day and will
be prescribed paracetamol 500 mg 2-3 times per day 2 tablets, or ibuprofen 400
mg 3 times a day during five days, after which they can the treatment if
necessary.
They will receive a diary to record symptoms and possible adverse reactions for
two weeks, this will take about 2 minutes a day. Also, they will be asked to
fill out the SF-12 health survey after 7 and 14 days.
After a week they will be asked to deliver a second urine sample to their GPs
practice. After two weeks they will be asked to send the diary to the
coordinating investigator. After these two weeks, follow-up is finished.
GPs will also be asked to record the number of eligible patients who decide not
to participate, without registration of personal information.

Women who agree to participate will be advised to drink at least 2 litres of
liquids per day and will be prescribed paracetamol 500 mg 2-3 times per dag 2
tablets or ibuprofen 400 mg 3 times a day during five days, after which they
can proceed the treatment if necessary.

The risk of complications of an uncomplicated UTI if not treated with
antibiotics, can not be eliminated completely. In two recent trials by
Christiaens et al. and Ferry et al., two cases of pyelonephritis were reported
in the control groups (including 463 subjects in total).[7,8] Ferry et al.
found one case of pyelonephritis in the antibiotic group (including 1143
subjects).[8]
Since the aforementioned placebo-controlled trials showed very few
complications in the control group, we think the risk of not treating is
acceptable. In addition, many women already follow a wait-and-see policy when
they start having symptoms and experience that the symptoms usually disappear
within few days.
The risk of pregnancy will not be eliminated by a pregnancy test, but it will
be minimized by asking the subject what the chances of pregnancy are. If the
subject can not be sure whether she is not pregnant, she will be excluded from
participation.
The filling out and handing in of the diary and questionnaires, and the handing
in of the urine sample will take about 80 minutes in total in 14 days.
A direct advantage to the subjects is the significantly reduced risk of side
effects of paracetamol, compared to antibiotics (such as diarrhea, skin rash),
because the normal bacterial flora is left intact.
A second advantage is less development of resistance to antibiotics in the
society.
This study provides a relatively inexpensive and rapid insight into the
acceptability of a symptomatic treatment of UTIs, and may provide the basis for
a large randomized placebo-controlled trial.
Also, it serves the opportunity to obtain a better insight into the natural
course of an uncomplicated UTI, with a small risk of complications.