Bacterial Interference for Prevention of Catheter-Associated UTI: Geriatric Pilot Study
Bacterial Interference for Prevention of Catheter-Associated UTI: Geriatric Pilot Study
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
 cultures.

 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.
Inclusion Criteria:

 -  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

 -  Have pre-existing bladder colonization

 Exclusion Criteria:

 -  obstructive urolithiasis

 -  percutaneous nephrostomy catheters

 -  supravesicular urinary diversion

 -  vesicoureteral reflux

 -  active malignancy

 -  uncontrolled diabetes mellitus

 -  AIDS

 -  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

 -  Prisoners

 -  Significant known mental illness or emotional disorder related to organic or inorganic
 causes

 -  subjects who are not capable of giving informed consent will not be included unless
 the subject's designated decision-maker is readily available