Response to antibiotics of women with symptoms of urinary tract infection but negative dipstick urine test results: double blind randomised controlled trial
BMJ 2005; 331 doi: https://doi.org/10.1136/bmj.38496.452581.8F (Published 14 July 2005) Cite this as: BMJ 2005;331:143
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Sir,
We read with interest the article by Richards et al (1) which raises
some interesting points on the diagnosis and treatment of Uropathogens.
The concept of significant bacteriuria was developed by Kass and
colleagues in the mid-1950s, on the basis that quantitative culture could
help distinguish between the presence of bacteria multiplying in the urine
and bacteria introduced as contaminants from the urethra or introitus
during voiding of a midstream sample of urine. Based on the fact that most
urinary tract infections are caused by Escherichia coli and related Gram-
negative bacteria that multiply rapidly in urine, significant bacteriuria
was defined as a microbial count of greater than 100 000 colony-forming
units (cfu) per ml (2), although even using this criterion a single
culture has up to a 20% chance of representing contamination only (3).
Following the widespread adoption of quantitative urine cultures, it
was noted that 20% to 40% of women with symptoms of acute urinary tract
infection (UTI) have bacterial counts of less than 100 000 cfu per ml.
Further evidence that UTI can be associated with bacterial counts of less
than 100 000 cfu per ml stems from the observations that the species of
bacteria isolated from these women are the same as those from women with
higher bacterial counts, bacteria can be isolated from urine samples
collected directly from the bladder (e.g. by catheterization or suprapubic
aspiration), and symptoms often respond to antimicrobial therapy. Some
studies have reported that bacterial counts as low as 100 cfu per ml can
be associated with symptoms. However, up to 10% of asymptomatic women have
bacterial counts of this magnitude in urine. As the bacterial count
increases within the range 100 to 100 000 cfu per ml the greater the
association with symptoms and in the magnitude of pyuria. Thus there is no
reliable cut-off for bacteriuria to be considered significant, but the
importance of bacterial counts of less than 100 000 cfu per ml should be
assessed in the light of symptoms and pyuria. There are various possible
explanations for the finding of low level bacteriuruia in symptomatic UTI,
including concurrent use of antimicrobials or that it represents an early
phase of the infection.
We note that 40% of the samples whilst having a negative dipstick had
pyuria on microscopy. Although microscopic findings did not predict
response to treatment, it is unlikely that the study was adequately
powered to verify this. To our reading these data demonstrate that a
negative dipstick does not reliably exclude UTI in symptomatic women.
The results of this study may be partly explained by the infection being
in an early phase, and therefore associated with low level bacteruria and
pyuria prior to an imflammatory response. To these ends data on the
duration of symptoms prior to presentation would be helpful in
interpreting the results before we throw the baby out with the bathwater.
Yours Faithfully
Philip Toozs-Hobson
Consultant Urogynaecologist
James Gray
Consultant Microbiologist
Arri Coomarasamy
Specialist Registrar
Birmingham Women’s Hospital,
Birmingham UK
1. Response to antibiotics of women with symptoms of urinary tract
infection but negative dipstick urine test results:double blind randomised
controlled trial Dee Richards, Les Toop, Stephen Chambers, Lynn Fletcher.
BMJ 2005;331, 143-146
2. Kass EH. Asypmtomatic infections of the urinary tract. Trans Assoc
Am Phys. 1956; 69: 56-64.
3. Kass EH. The role of asypmtomatic bacteriuria in the pathogenesis
of pyelonephritis. In Quinn EL, Kass EH (eds). Biology of Pyelonephritis.
Boston: Little, Brown 1960: 399-406.
Competing interests:
None declared
Competing interests: No competing interests
In
my experience the commonest cause of dysuria is soap. Therefore it seems bad
advice to treat this disorder with antibiotics without further investigation, as
suggested by Dr. Richards and coworkers.1 In a prospective study of
women, who consulted me because of dysuria and/or frequency I found that all of
14 women with the urethral syndrome (dysuria without bacteriuria), 15/17 with
uncomplicated, lower urinary tract infection (dysuria with bacteriuri), but only
6/19 with asymptomatic bacteriuria used soap or other detergents on the sexual
organs regularly.2
All women were advised to use water only and
women with a positive urine culture were treated with trimetoprim for three days.
At follow-up 22 of the 31 women with dysuria had stopped or substantially
reduced their use of soap. In seventeen dysuria had disappeared completely after
1-8 weeks. In contrast, six out of seven who did not follow my advice had still
dysuria.
Interestingly, recurrences of bacteriuria were
asymptomatic. Evidently, soap washing of the outer genitals rather than bacteria
seems to be the primary cause of dysuria. As there is no evidence that
asymptomatic bacteriuria in non-pregnant women has any adverse health effects, a
better treatment of dysuria, whether bacteriuria is present or not, is to ask
the women to wash with water only.
- Richards D, Toop L,
Chambers S, Fletcher L. Response to antibiotics of women with symptoms of
urinary tract infection but negative dipstick urine test results: double
blind randomised controlled trial. BMJ 2005;331:143-147. - Ravnskov U. Soap is
the major cause of dysuria. Lancet 1984;2:1027-8.
Competing interests:
None declared
Competing interests: No competing interests
Authors reply: Diagnosis of urinary infection
We would like to respond to the points raised by Philip Toozs-Hobson
and colleagues regarding our RCT of antibiotic treatment of women with
symptoms of urinary tract infection but negative dipstick urine test
results.
Low count bacteriuria/pyuria and response to treatment:
Only 6 participants had low count bacteriuria and they were evenly
distributed between the placebo and treatment groups. Of those in the
treatment group only one responded. We calculated the treatment effect
removing those women with pyuria and the effect persisted and was still
significant (ƒÓ2 =7.82 df =1, p=0.005). We also removed all those with low
count bacteriuria or pyuria and calculation showed that the effect
persisted and was still significant (ƒÓ2 =8.33, df =1, p=0.004).
Early stage UTI:
We assessed, independently of low count bacteriuria on initial MSU, the
possibility of this group of women simply representing "early but
ordinary" UTI. We believe this is unlikely for two reasons. We collected
a second MSU specimen on all women at day 7. Only 3 women in the placebo
group grew a uropathogen in their MSU at 7 days suggesting that this group
were not simply in the early stages of UTI development. We also assessed
duration of dysuria prior to treatment in the dipstick negative group The
duration of dysuria (median four days) was in fact longer than in a group
of dipstick positive women recruited to another study simultaneously
(median 2 days).
We agree that infection is the most likely cause of symptoms -
presumably either with very low numbers of conventional organisms or with
organisms not being recognised. However these data suggest that neither
dipstick testing nor routine laboratory testing are detecting this
infection. We therefore believe that negative dipstick and negative urine
findings cannot be relied on as intermediate predictors of those unlikely
to benefit from treatment. Until we have better methods of predicting who
will respond to antibiotics, empirical treatment of all with symptoms of
uncomplicated UTI seems appropriate.
Dee Richards
Les Toop
Stephen Chambers
Lynn Fletcher
Competing interests:
None declared
Competing interests: No competing interests