This study is a prospective pilot clinical trial investigating the use of urinary catheters
coated with benign E. coli in geriatric subjects.
1. Preparation of study catheters: Urinary catheters will be incubated in broth with E.
coli 83972 for 48 hours prior to insertion into patients. Samples of broth will be
removed after 24 hours and 48 hours of incubation to test for purity of the E. coli
83972. Study catheters will be inserted after 48 hours of incubation, unless
contamination was seen on the 24-hour plates. The 48-hour plates will be read at 72
hours, and any contamination would prompt removal of the study catheter. For subjects
who require antibiotics to clear their bladders prior to catheter insertion, we will
use a derivative strain of E. coli 83972 with the appropriate antibiotic resistance.
2. Screening procedures: Eligible subjects will be identified by chart review and by
discussion with health care providers. Research personnel will also periodically assess
the inpatient geriatric beds and review upcoming appointments in the geriatric and
urology clinics at the MEDVAMC. Potential outpatient subjects may be contacted by
telephone before their clinic appointment to advise them of the study. Those wishing to
participate will meet with study personnel in person when they come for their clinic
appointment. At the time of enrollment, the principal investigator or the research
coordinator will explain the study protocol in detail, and subjects will be given a
chance to ask questions. Informed consent will be obtained from interested persons at
that time. Any necessary screening procedures (history and physical examination, renal
ultrasound, serum creatinine, baseline urine culture) will be performed after obtaining
informed consent. Subjects who have not had a renal ultrasound within the past 12
months, or a serum creatinine measured within the past 6 months, will undergo these
procedures. Also, study personnel will collect urine for culture to determine what
organisms are present in the subject's bladder at baseline. The subject may receive
7-10 days of appropriate antibiotics to clear their bladders before insertion of study
catheters, depending on the pre-existing bladder flora.
3. Insertion of study catheters: Subjects requiring fluoroquinolone antibiotics to clear
their bladders will receive a study catheter 4-5 days after completing treatment.
Subjects requiring any other class of antibiotics will receive a study catheter 2-3
days after completing antibiotic treatment. The study catheter will be inserted in by
research personnel or by the unit nurse. Insertion will be performed using sterile
technique. Urine will be collected through the newly inserted study catheters and
cultured by study personnel.
4. Urine sample collection: Urine samples will be collected through the study catheter on
days 1, 3, 7, 14, 21, and 28 after catheter insertion. Urine will be mailed to the PI's
laboratory at the MEDVAMC in biological sample collection containers via overnight mail
for outpatients, or the samples can be collected directly from inpatients.
5. Study catheter removal: A day 28 urine sample will be collected through the study
catheter immediately prior to removal. Study catheters will be removed by study
personnel at the MEDVAMC. Subjects who still have E. coli 83972 on the day of catheter
removal will be given the option of taking antibiotics to eradicate the E. coli 83972
from the bladder or to remain colonized and in the follow-up phase of the study.
6. Specimen mailing procedure: We have utilized these specimen mailing supplies before.
The study organism, E. coli 83972, has 83% survival after 72 hours in the specimen
mailer tubes, when mailed from other locations in Texas and Louisiana. Both the study
organism and other uropathogens have likewise been recovered from urinary catheters
removed 72 hours previously and sent to us in specimen mailing tubes.
7. Microbiologic studies: Semi-quantitative cultures will be performed on each urine
sample to determine whether E. coli 83972 is present and the relative concentration of
each other species in the urine. The presence in the urine of bacteria other than E.
coli will be examined using standard bacteriological methods only. E. coli strains will
be assessed using standard microbiological techniques as well as molecular techniques
in the research laboratory. Urine will be spread on MacConkey lactose agar plates and
incubated to allow bacterial growth. Representative E. coli colonies will be subjected
to restriction fragment length polymorphism (RFLP) analysis using pulse field gel
electrophoresis (PFGE) to definitively identify E. coli 83972. The removed urinary
catheters will be sonicated to extract surface-associated organisms. An aliquot of each
sonicate will be plated for identification of organisms.
8. Defining outcomes: We will assess the safety and colonization success. For the purposes
of this study, we will define successful bladder colonization as persistence of E. coli
83972 in the urine for > 28 days after insertion of the catheter. Shorter duration of
colonization will be defined as failure to colonize the bladder. We will also compare
the incidence of symptomatic UTI while colonized with E. coli 83972 to the incidence of
symptomatic UTI experienced by the subjects in the year prior to study entry.
9. Safety assessment: The principal investigator will contact subjects daily for the first
3 days while they are wearing the study catheters, weekly for the remainder of the
first 28 days after insertion of the study catheter, and monthly thereafter as long as
they remain colonized with E. coli 83972. Subjects will be instructed to contact study
personnel for signs or symptoms of UTI, catheter malfunction, or need for antibiotics.
10. UTI in elderly subjects can present with constitutional symptoms rather than those
localized to the urinary tract, and the fever response can be blunted in the elderly.
Symptomatic UTI will be defined as the presence of significant bacteriuria (>102
cfu/ml), pyuria (>10 WBC/hpf) plus > 1 of the following signs and symptoms: fever (>
100.0 F), suprapubic or flank discomfort, bladder spasm, malaise, altered functional
status, or altered mental status, provided that no other etiologies for these clinical
manifestations can be identified. Subjects' baseline incidence of UTI in the year prior
to enrollment will be determined by chart review. Any documented treatment for UTI will
be regarded as a symptomatic UTI. We will also inquire whether patients were treated
for UTI at an outside facility. Subjects who develop symptomatic UTI will be treated
with antibiotics guided by susceptibility patterns for the organism(s) grown from urine
11. Duration of participation: If a subject remains colonized with E. coli 83972 on day 28
after removal of the study catheter, and if the subject declines antibiotics to
eradicate the study organism, we will continue to collect monthly urine specimens until
the organism is lost from the bladder or until completion of 12 months, whichever comes
first. Thus, an individual subject's participation in the study will be limited to 12
months or less.
- Patients followed at the MEDVAMC
- Require an indwelling bladder catheter (either transurethral or suprapubic)
- Have a history of at least 1 UTI in the past will be eligible for enrollment
- obstructive urolithiasis
- percutaneous nephrostomy catheters
- supravesicular urinary diversion
- vesicoureteral reflux
- active malignancy
- uncontrolled diabetes mellitus
- requirement for immunosuppressive medication, expected survival < 6 months,
creatinine clearance > 2.0 mg/dL, or current antibiotic therapy
- Latex allergy
- Allergic to 2 or more classes of drugs to which the urinary isolate is susceptible
- Prostate cancer on hormonal therapy with or without any surgery or radiation therapy
anticipated within the next 6 months
- Significant known mental illness or emotional disorder related to organic or
- subjects who are not capable of giving informed consent will not be included unless
the subject's designated decision-maker is readily available