*Midstream urine culture collected at time of enrollment urinary tract
infection yielded less than 102 colony-forming units per milliliter.
A, P<.001. B, P =
.004 for the comparison of ciprofloxacin vs amoxicillin-clavulanate (susceptible); P = .17 for the comparison of amoxicillin-clavulanate (susceptible)
vs amoxicillin-clavulanate (nonsusceptible). UTI indicates urinary tract infection.
Hooton TM, Scholes D, Gupta K, Stapleton AE, Roberts PL, Stamm WE. Amoxicillin-Clavulanate vs Ciprofloxacin for the Treatment of Uncomplicated Cystitis in WomenA Randomized Trial. JAMA. 2005;293(8):949-955. doi:10.1001/jama.293.8.949
Author Affiliations: Department of Medicine,
School of Medicine (Drs Hooton, Gupta, Stapleton, and Stamm and Ms Roberts),
Department of Epidemiology (Dr Scholes), School of Public Health and Community
Medicine, University of Washington, Seattle; and the Center for Health Studies,
Group Health Cooperative Seattle, Wash (Dr Scholes). Dr Gupta is now with
the Department of Medicine, Yale University, New Haven, Conn.
Context The high prevalence of resistance to trimethoprim-sulfamethoxazole and
other antimicrobials among Escherichia coli causing
acute cystitis in women has led to increased use of alternative antibiotics.
One such antibiotic, amoxicillin-clavulanate, has not been well studied.
Objective To compare the efficacy of a 3-day regimen of amoxicillin-clavulanate
to that of a 3-day regimen of ciprofloxacin in the treatment of acute cystitis
in women. The primary study hypothesis was that the amoxicillin-clavulanate
and ciprofloxacin treatment groups would differ in clinical cure.
Design, Setting, and Patients Randomized, single-blind treatment trial of 370 women, aged 18 to 45
years, with symptoms of acute uncomplicated cystitis and a urine culture with
at least 102 colony-forming units of uropathogens per milliliter
from a university student health center or a health maintenance organization.
Interventions Women were randomly assigned to receive amoxicillin-clavulanate (500
mg/125 mg twice daily) or ciprofloxacin (250 mg twice daily) for 3 days and
were followed up for 4 months.
Main Outcome Measures The main outcome measure was clinical cure. Secondary study outcomes
of interest were microbiological cure and vaginal E coli colonization at the 2-week follow-up visit.
Results Clinical cure was observed in 93 (58%) of 160 women treated with amoxicillin-clavulanate
compared with 124 (77%) of 162 women treated with ciprofloxacin (P<.001). Amoxicillin-clavulanate was not as effective as ciprofloxacin
even among women infected with strains susceptible to amoxicillin-clavulanate
(65 [60%] of 109 women in the amoxicillin-clavulanate group vs 114 [77%] of
149 women in the ciprofloxacin group; P = .004).
The difference in clinical cure rates occurred almost entirely within the
first 2 weeks after therapy. Microbiological cure at 2 weeks was observed
in 118 (76%) of 156 women treated with amoxicillin-clavulanate compared with
153 (95%) of 161 women treated with ciprofloxacin (P<.001).
At this visit, 45% of women in the amoxicillin-clavulanate group compared
with 10% in the ciprofloxacin group had vaginal colonization with E coli (P<.001).
Conclusions A 3-day regimen of amoxicillin-clavulanate is not as effective as ciprofloxacin
for the treatment of acute uncomplicated cystitis, even in women infected
with susceptible strains. This difference may be due to the inferior ability
of amoxicillin-clavulanate to eradicate vaginal E coli,
facilitating early reinfection.
Acute uncomplicated urinary tract infections (UTIs) are among the most
commonly encountered bacterial infections in women. Management of these infections
has been made more complicated in recent years by increasing antimicrobial
resistance, especially to β-lactams and trimethoprim-sulfamethoxazole.
The current standard for the empirical treatment of acute uncomplicated cystitis
is trimethoprim-sulfamethoxazole for 3 days. Because the prevalence of resistance
to trimethoprim-sulfamethoxazole among uropathogens is increasing, however,
fluoroquinolones are increasingly being used as empirical therapy for the
management of cystitis.1,2
Increasing fluoroquinolone resistance in many pathogens causing health
care–associated and community-acquired infections has raised concerns
about the future usefulness of this potent and frequently prescribed class
of antibiotics.3 It is important, therefore,
that fluoroquinolone-sparing antibiotics be used when appropriate. In the
case of acute cystitis, nitrofurantoin and fosfomycin tromethamine have been
advocated as fluoroquinolone-sparing alternatives to trimethoprim-sulfamethoxazole.4 Amoxicillin is not recommended for the empirical treatment
of UTIs because of the high prevalence of resistance associated with this
drug,4 but use of amoxicillin-clavulanate is
increasing.2 However, there are few data on
the efficacy of short-course amoxicillin-clavulanate regimens for treatment
of cystitis, and there are no published studies on the efficacy of amoxicillin-clavulanate
in the treatment of acute cystitis in the current era of high-level amoxicillin
resistance. We therefore compared, via a single-blind randomized trial, 3-day
regimens of amoxicillin-clavulanate and ciprofloxacin for treatment of women
with acute uncomplicated cystitis and used long-term follow-up to evaluate
recurrent infection. We also evaluated the effects of these antibiotics on
vaginal colonization with Escherichia coli and the
relationship of these effects to recurrent infection.
The study was conducted at the University of Washington Student Health
Center and at Group Health Cooperative from July 1998 to May 2002. The University
of Washington Student Health Center provides primary care for approximately
85% of the 34 000 students enrolled in the university. Group Health Cooperative
is a mixed-model health maintenance organization with approximately 475 000
enrollees located in western Washington State.
This treatment trial fulfilled 1 of the 5 primary aims of a large randomized
longitudinal study to examine the effects of antimicrobials on UTI recurrence
and vaginal flora. For investigating the question of difference in UTI recurrence
between the antibiotic treatment groups, the sample size was estimated to
provide greater than 90% power to detect a difference of 20% or more between
the 2 groups.
Women were eligible for enrollment if they were healthy, between 18
and 45 years of age, and had dysuria, frequency, and/or urgency. Women were
ineligible for enrollment if they were pregnant or if they had evidence of
pyelonephritis (such as temperature greater than 38°C, severe back pain,
or costovertebral angle tenderness), history of significant allergy to a fluoroquinolone
or penicillin, a chronic illness requiring medical supervision, a known anatomic
or functional abnormality of the urinary tract, or had received systemic or
vaginal topical antimicrobials within the previous 14 days.
The Human Subjects Review Committees of the University of Washington
and Group Health Cooperative approved the study, and all patients gave written
At the initial visit, participants underwent a directed history and
physical examination, an interview using a standardized study questionnaire,
a midstream urine specimen collection to evaluate bacteriuria and pyuria,
and a vaginal swab specimen collection to evaluate bacterial colonization.
Race and ethnicity were self-reported on the questionnaire. Participants were
randomized to treatment assignments by the statistician, using a blocked randomization
scheme with varying block sizes not revealed to clinic personnel. Assignments
were placed in sealed, sequentially numbered envelopes, which were opened
at the time of enrollment. Women received either amoxicillin-clavulanate (500
mg/125 mg twice daily) or ciprofloxacin (250 mg twice daily) each for 3 days.
They were asked to return to the clinic every 2 weeks for 4 months or until
they were retreated for symptomatic persistent or recurrent UTI. At each visit,
the tests performed at the initial visit were repeated. At the first follow-up
visit (2 weeks), participants were asked how many study pills they had taken.
Methods for collecting urine and vaginal specimens and isolating, identifying,
and quantifying urine and vaginal uropathogens have been previously described.5,6 Vaginal cultures were considered positive
for E coli if there was ≥1+ growth on a semiquantitative
scale. The Kirby-Bauer disc method was used to determine antimicrobial susceptibility
of causative strains. The leukocyte esterase test was performed on each midstream
urine specimen and categorized as positive if at least trace.
Genomic DNA isolation, restriction endonuclease digestion, gel electrophoresis,
and Southern blot hybridization were performed as previously described.7 Total E coli ribosomal RNA
(Sigma, St Louis, Mo) was radioactively labeled by extension of random primers
using reverse transcriptase.8 Ribotyping was
performed using PvuII and Eco RI. Only
isolates showing 100% match in the restriction fragment length polymorphism
patterns were classified as identical to each other.
The primary study outcome was study drug efficacy based on clinical
cure. Women were considered to have clinical cure if they did not have symptomatic
persistent or recurrent UTI. A woman was considered to have a persistent UTI
if, following study drug treatment, she had persistent symptoms warranting
retreatment. A woman was considered to have a recurrent UTI if she had resolution
of her initial UTI symptoms after treatment but then developed recurrent symptoms
warranting retreatment. A persistent or recurrent UTI was considered to be
culture-confirmed if there were at least 102 colony-forming units
(CFU) of uropathogens per milliliter of urine.
Secondary study outcomes were (1) study drug efficacy based on microbiological
cure at the first posttreatment visit (2 weeks); (2) vaginal colonization
with E coli at all posttreatment visits; and (3)
the association between vaginal colonization with E coli and symptomatic persistent or recurrent UTI. Women were considered
microbiologically cured if, at an asymptomatic 2-week follow-up visit, they
had less than 105 CFU/mL of all uropathogens and at least a 1-log
drop in colony count of the causative uropathogen compared with the urine
culture at enrollment. Women who had persistent or recurrent UTI symptoms
warranting retreatment before the 2-week visit were also classified as microbiologically
cured if their urine cultures had less than 102 CFU/mL and they
were not taking antibiotics at the time of the urine culture.
The associations between antimicrobial susceptibility of the initially
infecting strains and clinical and microbiological outcomes were evaluated.
For culture-confirmed UTIs, uropathogens with the highest colony count were
considered the causative pathogen, but if 2 or more organisms had the same
colony count (within <1 log) they were considered copathogens. Coagulase-negative
staphylococci, α-hemolytic streptococci, lactobacilli, diphtheroids,
and mixed gram-positive flora were categorized as nonuropathogens at enrollment
All women who were enrolled and randomized to receive treatment were
included in analyses of demographic and behavioral characteristics and UTI
history, using means and frequency distributions. Women were included in the
analysis if they met enrollment criteria, had at least 102 CFU/mL
of uropathogens in their enrollment urine, and returned to the clinic for
at least 1 postrandomization clinic visit. Infecting uropathogens at the enrollment
UTI were also described, as well as their antibiotic susceptibility profiles.
Kaplan-Meier curves were constructed to examine the cure rates over
the follow-up period, and the likelihood ratio test was used to test for differences
between treatment groups. Comparisons of proportions between the 2 treatment
groups were tested using the χ2 statistic. Women were followed
up until they were retreated for persistent or recurrent UTI symptoms or the
end of the study. SAS version 8.2 (SAS Institute, Cary, NC) was used for all
analyses. Statistical significance was considered to be P<.05.
Three hundred seventy women (335 at the student health center and 35
at Group Health Cooperative) were enrolled and randomized to receive treatment
(Figure 1). Women randomized to the
2 treatment groups and included in the efficacy analyses were similar with
respect to baseline characteristics (Table 1).
Forty-eight women were excluded from the analyses: 39 had less than 102 CFU/mL at enrollment and 9 had no follow-up. The 322 women eligible
for the analyses (160 randomized to receive amoxicillin-clavulanate and 162
randomized to receive ciprofloxacin) were followed for a median of 103 days
(range, 2-125 days). Compliance with at least 5 of the 6 doses of study drug
was 99% in both groups. Women taking fewer than 6 doses of study drug were
included in the analyses.
Among the 370 women enrolled, 331 women had 1 or more uropathogens present
in quantities of at least 102 CFU/mL. Escherichia
coli was the only pathogen or copathogen in 270 (82%), group B streptococci
in 28 (8%), Staphylococcus saprophyticus in 26 (8%),
enterococci in 8 (2%), and Klebsiella species and Proteus mirabilis in 7 (2%) each. Overall susceptibility
data for the 323 isolates tested are shown in Table 2. Susceptibility data for the E coli strains
were almost identical. Among the 99 isolates that were resistant to ampicillin,
36% were susceptible, 33% were intermediate, and 30% were resistant to amoxicillin-clavulanate.
Among the 31 isolates that were intermediately resistant to ampicillin, 65%
were susceptible to amoxicillin-clavulanate.
Clinical Outcomes. The rate of clinical cure
was significantly lower in the amoxicillin-clavulanate group (93 [58%] of
160) than in the ciprofloxacin group (124 [77%] of 162) (P<.001) (Figure 2). The women
in the amoxicillin-clavulanate group had a significantly lower clinical cure
rate compared with women in the ciprofloxacin group regardless of whether
the patients were infected with strains that were susceptible (65 [60%]of
109 women in the amoxicillin-clavulanate group vs 114 [77%] of 149 women in
the ciprofloxacin group; P = .004) or nonsusceptible
(34 women) (P = .001 vs ciprofloxacin)
to amoxicillin-clavulanate (Figure 2).
Although there was a trend toward a better clinical outcome in women treated
with amoxicillin-clavulanate if they were infected with strains susceptible
to amoxicillin-clavulanate, this difference was not statistically significant
(P = .17) (Figure 2). In addition, among the 109 women in the amoxicillin-clavulanate
group infected with amoxicillin-clavulanate–susceptible uropathogens,
cure rates were not associated with amoxicillin susceptibility of the infecting
Persistent UTIs occurred in 8 women treated with amoxicillin-clavulanate
(3 had susceptible strains at enrollment) and in 1 woman treated with ciprofloxacin
(the strain was susceptible) (Table 3).
Recurrent UTIs occurred in 59 women in the amoxicillin-clavulanate group and
37 women in the ciprofloxacin group. Among the 67 persistent or recurrent
UTIs in the amoxicillin-clavulanate group, 33 (50%) occurred within the first
2 weeks (Table 3) and 34 occurred during
weeks 3 through 10 following treatment compared with 3 (8%) and 35 (92%),
respectively, of the 38 persistent or recurrent UTIs in the ciprofloxacin
group. Persistent and recurrent UTIs were culture-confirmed in 51 (76%) women
treated with amoxicillin-clavulanate compared with 30 (79%) women treated
with ciprofloxacin. Pyuria was present in 92% of the women who had persistent
or recurrent UTI in each of the 2 treatment groups.
In the amoxicillin-clavulanate group, all 3 pairs of initial and persistent
UTI strains tested and 16 (73%) of 22 pairs of initial and recurrent UTI strains
tested had the same ribotype.
Five women infected with amoxicillin-clavulanate–susceptible strains
of E coli at enrollment who were treated with amoxicillin-clavulanate
had recurrent UTIs 7 to 44 days after treatment caused by E coli strains that were nonsusceptible to amoxicillin-clavulanate.
Isolates from only 1 such patient had the same ribotype. Two women treated
with ciprofloxacin whose original uropathogens were susceptible to ciprofloxacin
developed recurrent UTI with ciprofloxacin-nonsusceptible strains 20 and 29
days after treatment—both were different species from the originally
Two women in the amoxicillin-clavulanate group who at 2 weeks after
treatment had persistent bacteriuria with at least 105 CFU/mL of E coli and pyuria but no urinary symptoms were subsequently
diagnosed with and treated for pyelonephritis. Because they were asymptomatic,
these 2 women did not receive treatment at the 2-week visit. One woman presented
3 days after her 2-week follow-up visit to the emergency department with subjective
fever and chills and acute onset of back pain and was found to have a temperature
of 38.5°C, bilateral mild costovertebral angle tenderness, pyuria, and
greater than 105 CFU/mL of E coli, which
was susceptible to amoxicillin-clavulanate. Her initial, 2-week follow-up,
and pyelonephritis strains were identical by ribotype. The other woman presented
to an outside hospital 5 days after her 2-week visit with subjective fever
and shaking chills, urgency, and low back pain and reported that she had a
temperature of 39.8°C. We were not able to obtain her outside medical
records or laboratory isolate, but her initial and 2-week isolates were identical
Microbiological Outcomes. Microbiological cure
was also inferior in the amoxicillin-clavulanate group. At the 2-week posttreatment
visit, microbiological cure was observed in 118 (76%) of 156 women in the
amoxicillin-clavulanate group compared with 153 (95%) of 161 women in the
ciprofloxacin group (P<.001) (Table 3). In the amoxicillin-clavulanate group, microbiological
cure occurred in 77 (73%) of 106 women infected with susceptible strains compared
with 27 (82%) of 33 women infected with nonsusceptible strains (P = .30). In the amoxicillin-clavulanate group, 66% of the
women with microbiological failure had symptomatic persistent or recurrent
UTI compared with 13% in the ciprofloxacin group (Table 3).
Vaginal Colonization withE coli. Vaginal colonization with E coli was
present at enrollment in 82% (130/159) of the women in the amoxicillin-clavulanate
group compared with 86% (139/162) in the ciprofloxacin group (Figure 3). By the 2-week posttreatment follow-up visit,
however, 45% (68/151) of the women in the amoxicillin-clavulanate group compared
with 10% (16/153) in the ciprofloxacin group had vaginal colonization (P<.001). This difference did not narrow until week 10
after treatment. Antimicrobial susceptibility testing was not performed on
vaginal isolates at enrollment and, thus, we were not able to determine the
relationship between antimicrobial susceptibility of the vaginal strains at
enrollment and the prevalence of posttreatment colonization.
There was a trend toward presence of vaginal colonization with E coli at the 2-week posttreatment visit and subsequent
recurrent UTI over the next month. Thus, recurrent UTIs occurred in 44 (21%)
of 213 women who did not have vaginal colonization with E coli at the 2-week visit compared with 22 (31%) of 70 who had colonization
(P = .06).
Adverse Events. When asked an open question
about whether the participant had adverse effects related to study medications,
women in the amoxicillin-clavulanate group were more likely to report symptoms
(27%) compared with women in the ciprofloxacin group (19%) (P = .06). Differences were due mostly to increased loose
stools and vaginal symptoms in the women treated with amoxicillin-clavulanate.
Loose stools were reported in 8% and 0.6%, vaginal symptoms in 9% and 3%,
nausea in 5% and 8%, any central nervous symptoms in 3% and 6%, and fever
or rash in 1% and 0% of amoxicillin-clavulanate–treated and ciprofloxacin-treated
women, respectively. Twenty-two amoxicillin-clavulanate–treated women
required treatment for adverse effects compared with 10 ciprofloxacin-treated
women. Only 2 women in the amoxicillin-clavulanate group and 1 woman in the
ciprofloxacin group discontinued study medication due to adverse effects.
This is the first comparison of a 3-day regimen of amoxicillin-clavulanate
vs a 3-day regimen of a fluoroquinolone for the treatment of acute uncomplicated
cystitis in women. Amoxicillin-clavulanate was markedly inferior to ciprofloxacin
in clinical and microbiological cure rates as well as in eradication of vaginal E coli. Of concern, 2 women developed same-strain pyelonephritis
soon after treatment with amoxicillin-clavulanate (same-strain is presumed
in 1 woman based on a urine culture 5 days before the episode of pyelonephritis).
The difference in clinical cure occurred primarily within the first 2 weeks
of treatment and was most likely due to the inferior activity of amoxicillin-clavulanate
in eradicating E coli from the vagina. At the 2-week
follow-up visit, 45% of amoxicillin-clavulanate–treated women had vaginal
colonization compared with 10% of ciprofloxacin-treated women (Figure 3). In this regard, amoxicillin-clavulanate is similar to
ampicillin and amoxicillin, drugs that also do not effectively eradicate E coli from the vaginal reservoir and are associated with
high recurrence rates.9
Although not evaluated in this study, another factor that may have contributed
to the poorer results seen with amoxicillin-clavulanate is the much shorter
serum half-life of amoxicillin compared with ciprofloxacin (1.3 hours for
amoxicillin, 1 hour for clavulanate, and 4 hours for ciprofloxacin) and, thus,
the shorter period of time that amoxicillin is present in high concentrations
in urine. Although concerns have been raised about the effectiveness of amoxicillin-clavulanate
in the treatment of UTIs caused by amoxicillin-resistant E coli,10 we were unable to demonstrate
that amoxicillin-resistant strains were associated with higher failure rates.
Finally, it has been demonstrated in an experimental mouse model that E coli, following inoculation of large quantities into
the bladder, can penetrate into the bladder epithelium and produce intracellular
colonies of bacteria and eventually biofilms.11,12 If
epithelial invasion and biofilm formation occurs in human cystitis, it is
possible that amoxicillin-clavulanate is less effective than ciprofloxacin
in eradicating uropathogens from these sites, resulting in higher clinical
The worldwide increase in trimethoprim-sulfamethoxazole resistance in E coli and concerns about fluoroquinolone resistance in
UTIs and other more serious infections3 highlight
the need for alternative antibiotics for the treatment of cystitis. Nitrofurantoin
and fosfomycin tromethamine have both been advocated as fluoroquinolone-sparing
alternatives to trimethoprim-sulfamethoxazole, but neither appears to be as
effective as trimethoprim-sulfamethoxazole or fluoroquinolones.4,13 Although β-lactam
antibiotics have long been used for the treatment of UTIs, lower UTI cure
rates have generally been observed compared with trimethoprim-sulfamethoxazole
and fluoroquinolones regardless of the duration of treatment.4 Amoxicillin-clavulanate
has been used for the treatment of UTIs and other infections since the early
1980s, but most published trials of its efficacy have been very small, in
children or in mixed populations of patients, including those with complicated
UTIs.14- 23 In
studies of uncomplicated cystitis, a 3-day regimen of amoxicillin-clavulanate
and a 7-day regimen of trimethoprim-sulfamethoxazole have been shown to be
superior to a single-dose regimen of amoxicillin-clavulanate.24,25 Exposure
to amoxicillin-clavulanate has been shown previously to select for subsequent
amoxicillin-clavulanate–resistant E coli UTIs.26 In our study, 5 women originally infected with amoxicillin-clavulanate–susceptible
strains who were treated with amoxicillin-clavulanate were found to have recurrent
UTIs with strains nonsusceptible to amoxicillin-clavulanate, but only one
was genetically identical to the initial strain.
We chose to compare 3-day regimens of amoxicillin-clavulanate and ciprofloxacin
for the treatment of acute uncomplicated cystitis because of the need for
safe and effective fluoroquinolone-sparing antibiotics, the absence of a large
trial comparing a 3-day regimen of amoxicillin-clavulanate to current standard
therapy, and increasing amoxicillin-clavulanate use for the treatment of UTIs
over the past decade.2 The prevalence of amoxicillin-clavulanate
resistance among causative strains at baseline (9%) was in the same range
as that described in recent European countries (3.4% [range, 0%-9.3%]).27 The rate of amoxicillin-clavulanate resistance appeared
to have limited impact on both clinical and microbiological outcomes. In fact,
amoxicillin-clavulanate was found to be significantly inferior to ciprofloxacin
even in women infected with uropathogens susceptible in vitro to amoxicillin-clavulanate.
Strengths of this study include its large sample size, well-defined
study population, long follow-up period, low dropout rate, high rate of medication
adherence, and genetic analysis of strains causing persistent and early recurrent
UTIs. The single-blind study design is a potential weakness of the study if
there was a clinical bias against amoxicillin-clavulanate and a subsequent
lower threshold to treat women in this group who had mild symptoms. This seems
unlikely since the percentage of UTIs that were culture-confirmed and the
percentage that were associated with pyuria were almost identical in the 2
Trimethoprim-sulfamethoxazole should continue to be the first-line treatment
for acute cystitis if the woman has no history of allergy to the drug and
if the likelihood of trimethoprim-sulfamethoxazole resistance is low.4,28 In areas where the likelihood of trimethoprim-sulfamethoxazole
resistance is high (>20%) or in women who have risk factors for trimethoprim-sulfamethoxazole
resistance, nitrofurantoin or a fluoroquinolone is an appropriate choice.
Amoxicillin-clavulanate in a 3-day regimen is not as effective as a fluoroquinolone
for the treatment of acute uncomplicated cystitis, even in those women with
UTIs caused by susceptible uropathogens, and should be considered only when
use of other first- and second-line antibiotics is not feasible.
Corresponding Author: Thomas M. Hooton,
MD, Harborview Medical Center, 325 Ninth Ave (Box 359930), Seattle, WA 98104
Author Contributions: Dr Hooton had full access
to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Study concept and design: Hooton, Scholes,
Gupta, Stapleton, Roberts, Stamm.
Acquisition of data: Hooton, Stamm.
Analysis and interpretation of data: Hooton,
Scholes, Gupta, Stapleton, Roberts, Stamm.
Drafting of the manuscript: Hooton, Scholes,
Critical revision of the manuscript for important
intellectual content: Hooton, Scholes, Gupta, Stapleton, Roberts, Stamm.
Statistical analysis: Hooton, Scholes, Gupta,
Obtained funding: Hooton, Stamm.
Administrative, technical, or material support:
Hooton, Stapleton, Stamm.
Study supervision: Hooton, Scholes, Stamm.
Financial Disclosures: Dr Hooton has received
honoraria from Bayer for consulting and speaking, honoraria from Ortho McNeil,
Bristol-Myers Squibb, and GlaxoSmithKline for speaking, and research support
from MedImmune; Dr Gupta has received honoraria from Bayer, Procter and Gamble,
and Ortho McNeil for consulting and speaking, and research support from Procter
and Gamble; Dr Stamm has consulted and received research grants from Procter
and Gamble and MedImmune and consulted for Osel; and Ms Roberts has received
research support from Procter and Gamble.
Funding/Support: This study was supported by
grant 1 PO DK53369 from the National Institute of Diabetes and Digestive and
Kidney Diseases (Walter E. Stamm, principal investigator).
Role of the Sponsor: Representatives of Bayer
and Glaxo SmithKline had no input into the design or conduct of the study;
in the collection, management, analysis, or interpretation of the data; or
in the preparation, review, or approval of the manuscript. No support was
given by either company to conduct the study.
Acknowledgment: We wish to thank Elaine Jong,
MD, Medical Director, and the staff at Hall Health Center for helping with
subject enrollment, Carol Winter, ARNP, for subject enrollment and Natalie
DeShaw for assistance with patient care and data collection at Hall Health
Center and, at Group Health Cooperative, Fae Neumann, RN, and Kim Caudill,
BS, for helping with patient enrollment and data collection, Mansour Somadpour,
PhD, for performing strain ribotyping, and Marsha Cox, BS, Cheryl Wobbe, and
Sheila Manuguid, BS, at the University of Washington UTI Research Laboratory
for laboratory assistance.